epoetin-alfa and Kidney-Failure--Chronic

Hypertension among patients on hemodialysis is predominantly systolic (either isolated or combined with diastolic hypertension), whereas the scenario of isolated diastolic hypertension is rare and more common in younger patients. Uncontrolled hypertension that persists despite aggressive antihypertensive drug therapy is a reflection of the volume overload that is a prominent mediator of systolic and diastolic BP elevation. Clinical-trial evidence supports the notion that dry-weight probing is an effective strategy to improve BP control, even when overt clinical signs and symptoms of volume overload are not present. Accelerated arterial stiffness influences the patterns and rhythms of interdialytic ambulatory BP and is a major determinant of isolated systolic hypertension in hemodialysis. Posthoc analyses of the Hypertension in Hemodialysis patients treated with Atenolol or Lisinopril (HDPAL) trial, however, suggest that arterial stiffness does not make hypertension more resistant to therapy and is unable to predict the treatment-induced improvement in left ventricular hypertrophy. A combined strategy of sodium restriction, dry-weight adjustment, and antihypertensive medication use was effective in improving ambulatory BP control regardless of the severity of underlying arteriosclerosis in HDPAL. Other nonvolume-dependent mechanisms, such as erythropoietin use, appear to be also important contributors and should be taken into consideration, particularly in younger hemodialysis patients with diastolic hypertension. In this article, we explore the role of volume overload, arterial stiffness, and erythropoietin use as causes of systolic vs diastolic hypertension in patients on hemodialysis. We conclude with clinical practice recommendations and with a call for a "volume-first" approach when managing hemodialysis hypertension.

Topics: Atenolol; Diastole; Epoetin Alfa; Erythropoietin; Female; Follow-Up Studies; Humans; Hypertension; Incidence; Kidney Failure, Chronic; Lisinopril; Male; Renal Dialysis; Risk Assessment; Systole; Vascular Stiffness; Water-Electrolyte Imbalance

While prescribing biosimilars to patients naive to a biologic treatment is a well-accepted practice, switching clinically stable patients from an originator to a biosimilar is an issue for clinicians. Well-designed clinical trials and real-world data which study the consequences of switching from an originator biologic treatment to its biosimilar alternative are limited, especially for monoclonal antibodies. Areas covered: A systematic literature review was conducted on PubMed to identify evidence of the consequences of switching from original biologics to biosimilars. References of included papers were also scrutinized. After a title-, abstract- and full text screening, out of the 153 original hits and 77 additional ones from screening the references, 58 papers (12 empirical papers, 5 systematic reviews and 41 non-empirical papers) were included. Expert opinion: Preventing patients on biologic medicines from switching to biosimilars due to anticipated risks seems to be disproportional compared to the expected cost savings and/or improved patient access. Indeed, it is the opinion of the authors that the concern of switching to biosimilars is overhyped.

Topics: Anemia; Biosimilar Pharmaceuticals; Databases, Factual; Epoetin Alfa; Health Care Costs; Humans; Inflammatory Bowel Diseases; Kidney Failure, Chronic; Neoplasms; Red-Cell Aplasia, Pure; Rheumatic Diseases; Risk

Epoetin alfa (EPO) and darbepoetin alfa (DPO) are erythropoiesis-stimulating agents that are widely and interchangeably used for the treatment of anemia in patients with advanced chronic kidney disease and end-stage renal disease. No study has specifically compared the risks of hard study outcomes between EPO and DPO, including mortality.. Systematic review of the literature and meta-analysis.. Patients enrolled in randomized trials comparing EPO versus DPO for the treatment of anemia in adults with chronic kidney disease, including those requiring dialysis.. We conducted a systematic search of the literature (PubMed, CENTRAL, SCOPUS, and EMBASE, all years) and industry resources, using predefined search terms and data abstraction tools. We then summarized key characteristics and findings of these trials and performed a random-effects meta-analysis of trials with at least 3 months' duration to identify the summary OR of mortality between patients randomly assigned to DPO versus EPO.. DPO versus EPO.. All-cause mortality.. We identified 9 trials that met the stated inclusion criteria. Overall, 2,024 patients were included in the meta-analysis, of whom 126 died during follow-up, which ranged from 20 to 52 weeks. We found no significant difference in mortality between patients randomly assigned to DPO versus EPO (OR, 1.33; 95% CI, 0.88-2.01). No treatment heterogeneity across studies was detected (Q statistic=4.60; P=0.8).. Generalizability to nontrial populations is uncertain.. Few trials directly comparing DPO and EPO have been conducted and follow-up was limited. In aggregate, no effect of specific erythropoiesis-stimulating agent on mortality was identified, but the confidence limits were wide and remained compatible with considerable harm from DPO. Absent adequately powered randomized trials, observational postmarketing comparative effectiveness studies comparing these erythropoiesis-stimulating agents are required to better characterize the long-term safety profiles of these agents.

Topics: Anemia; Cause of Death; Darbepoetin alfa; Double-Blind Method; Epoetin Alfa; Erythropoietin; Half-Life; Hematinics; Humans; Kidney Failure, Chronic; Randomized Controlled Trials as Topic; Recombinant Proteins; Renal Dialysis; Renal Insufficiency, Chronic

Topics: Anemia; Biosimilar Pharmaceuticals; Epoetin Alfa; Erythropoietin; Europe; Hematinics; Humans; Hypoxia-Inducible Factor 1; Kidney Failure, Chronic; Recombinant Proteins; United States; United States Food and Drug Administration

Management of anaemia in chronic renal insufficiency (CRI) represents an important medico-economic challenge because of the great number of patients and the cost of the erythropoiesis-stimulating agent (ESA). The aim of this study was to identify determinants of the costs associated with these treatments in order to choose, with equal efficacy, the most efficient ASE.. A bibliographic research was realised by Medline database interrogation.. Among the direct medical costs, five studies showed that acquisition of epoetine alfa (EA) compared to darbepoetin alfa (DA) was less expensive. Concerning the costs associated with the route of administration, the subcutaneous injection (SC) of epoetine allowed a gain in costs because of the decrease of doses compared to the intravenous (IV) route. The switch from EA in SC to DA in IV, for hemodialysis patients, was associated with a reduction of the number of injections and with a treatment's cost lower by DA than by EA. Costs related to the regimen of administration, notably those related to nursing, medical and pharmaceutical time, were negligible towards those associated to the acquisition of the ASE. Finally, the costs of the therapeutic follow-up and treatment of the adverse effects of the ASE were similar between the EA and the DA.. The costs associated with the prices of acquisition of the ASE, negotiated by the structure of care, represent the most important part of the direct medical costs.

Topics: Anemia; Darbepoetin alfa; Direct Service Costs; Drug Costs; Epoetin Alfa; Erythropoietin; France; Health Care Costs; Hematinics; Humans; Injections, Intravenous; Injections, Subcutaneous; Kidney Failure, Chronic; Recombinant Proteins

The triad of diabetes mellitus, anemia, and chronic kidney disease (CKD) define a group of patients at high risk for death and cardiovascular complications. The approval of epoetin alfa in 1989 transformed the treatment of anemia in patients with CKD. However, evidence has emerged from randomized controlled trials that correcting anemia with erythropoiesis-stimulating agents in CKD patients is associated with increased risk. Most recently, the TREAT (Trial to Reduce Cardiovascular Events With Aranesp Therapy) study of anemic type 2 diabetic patients with CKD reported that treatment with darbepoetin conferred no benefit in mortality or in attenuating cardiovascular or renal events. Instead, there was a twofold higher rate of stroke and thromboembolic complications and a higher rate of cancer deaths in patients randomized to treatment with darbepoetin. Furthermore, there was an inconsistent and modest improvement in health-related quality of life. TREAT raises questions about whether anemia in type 2 diabetic patients should be treated and under what circumstances.

Topics: Anemia; Darbepoetin alfa; Diabetes Mellitus, Type 2; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Randomized Controlled Trials as Topic; Recombinant Proteins

epoetin zeta is a recently introduced recombinant erythropoietin, designed to be biologically similar to epoetin alfa. This posthoc analysis evaluated the impact of switching patients with chronic kidney disease (CKD) on hemodialysis from epoetin alfa to epoetin zeta, or vice versa, on hemoglobin concentration, epoetin dose, and patient safety.. data were analyzed from three published trials: two 24-week randomized, double-blind (maintenance and induction) studies and a 56-week, open-label, follow-on study involving adult patients with CKD stage 5, maintained on hemodialysis, and receiving epoetin alfa or epoetin zeta. Patients had either completed and switched treatments within the maintenance study, or had completed the induction or maintenance study on epoetin alfa and then switched to, and completed at least 12 weeks of follow-up treatment on, epoetin zeta. Mean hemoglobin levels and epoetin dose were evaluated pre- (0-4 weeks before) and post- (8-12 weeks after) switch, and were considered equivalent for the two treatments if the upper and lower limits of the 95% confidence intervals (CIs) for the intraindividual differences in mean values fell within accepted limits.. overall, 481 patients were included in the analysis. Mean hemoglobin concentration was maintained at target levels (10.5-12.5 g/dL) throughout the drug switch. The mean differences in hemoglobin concentration and associated 95% CIs following the switch remained within prespecified equivalence limits (± 1.0 g/dL). The 95% CIs of the mean difference in weekly epoetin dose postswitch also remained within prespecified equivalence margins (± 45 IU/kg; upper limit 17.83 IU/kg, lower limit -10.91 IU/kg). Both treatments were similarly well tolerated.. our data suggest that epoetin alfa and epoetin zeta therapy can be interchanged without any clinically significant alteration in efficacy, safety, or epoetin dose, in patients with CKD on dialysis receiving stable epoetin maintenance therapy.

Topics: Adult; Aged; Anemia; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Retrospective Studies; Therapeutic Equivalency; Young Adult

Topics: Anemia; Animals; Diabetic Nephropathies; Disease Progression; Epoetin Alfa; Erythropoietin; Female; Humans; Kidney Failure, Chronic; Male; Nephrotic Syndrome; Proteinuria; Quality of Life; Randomized Controlled Trials as Topic; Recombinant Proteins

Cardiovascular disease (CVD) is a major cause of mortality in patients with mild to moderate chronic kidney disease (CKD) and end-stage renal disease (ESRD). Dyslipidemia has been established as a well-known traditional risk factor for CVD in the general population and it is well known that patients with CKD exhibit significant alterations in lipoprotein metabolism. In this review the pathogenesis and treatment of renal dyslipidemia are discussed.. Studies on lipid abnormalities in CKD stages 1-4, in nephrotic syndrome, and in hemodialysis and peritoneal dialysis patients are analyzed, as well as the lipid profile of kidney graft recipients. Also, the results of the effects of epoietin treatment and hypolipidemic drugs in CKD patients are reported.. Disturbances in lipoprotein metabolism are evident even at the early stages of CKD and usually follow a downhill course that parallels the decline of renal function. However, several intrinsic or exogenous factors can influence the phenotypic expression of these alterations. According to the literature, current evidence suggests that unlike dialysis patients, mild to moderate CKD patients could be benefit from the use of statins.. The use of statins is indicated in patients with mild to moderate CKD, while in subjects with ESRD lipid-lowering therapy should be individualized.

Topics: Dyslipidemias; Epoetin Alfa; Erythropoietin; Humans; Hypertriglyceridemia; Kidney Failure, Chronic; Kidney Transplantation; Lipid Metabolism; Lipids; Models, Biological; Nephrotic Syndrome; Peritoneal Dialysis; Recombinant Proteins; Renal Dialysis; Treatment Outcome

Several recent articles have examined the time-dependent effects of epoetin therapy and the variability of hemoglobin (HGb) levels and what epoetin does in hemodialysis patients. A recent preliminary report also found that HGG cycling was common among hemodialysis patients, with only 10% of patients remaining within their initial HGb range (less than 11 g/dl, 11 to 12.5 g/dl, greater than 12.5 g/dl) during a six-month period. Factors associated with HGb cycling were changes in epoetin dose, intravenous-iron administration or a change in dose and hospitalization. What is not known is whether there are adverse clinical outcomes associated with HGb variability, although preliminary data indicate, perhaps predictably, that a decreasing HGb level is associated with a higher mortality risk. This is certainly an area that merits further study.

Topics: Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Recombinant Proteins; Renal Dialysis

The cardiovascular state and life quality of patients suffering from chronic renal insufficiency is primarily determined by their haemostatic status. Renal anemia can positively be diagnosed if the glomerular filtration rate diminishes significantly (<60 ml/min/1,73 m 2 ). Other causes of anemia besides renal insufficiency can be excluded in these instances. The primary aim of erythropoietin treatment is to abolish the transfusion demand of patients suffering from renal insufficiency as this could lead to antibody formation and the transduction of viral infections. In case the existence of renal anemia is proved, the target values must be determined. A target value of >11 g/dl hemoglobin should be achieved for at least 85% of the patients in order to get an average hemoglobin level of 12-12,5 g/dl for the whole patient population. During the treatment of renal anemia regulating the iron metabolism of patients is of primary importance. A >5% rate of the hypochromic red blood cells in the blood circulation implies iron deficiency; but a value above 10% positively indicates iron deficiency. The transferric saturation values under 20% indicate functional iron deficiency and this indicator is a good means of following iron treatment. In the case of patients receiving dialysis parenteral input is advised because of poor iron absorption. In national clinical practice several erythropoietin products are available (erythropoietin-alpha, erythropoietin-beta, alpha-darbepoetin and continuous erythropoietin receptor activator, a new product now being introduced). When selecting the appropriate treatment strategy for each patient, the application method, the effect range and cost efficiency of the selected erythropoietin product must be taken into consideration.

Topics: Anemia, Hypochromic; Darbepoetin alfa; Drug Resistance; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Quality of Life; Recombinant Proteins; Renal Dialysis

Recombinant human erythropoietin has been used for more than 20 years for the treatment of renal anaemia, with epoetin-alfa and -beta representing the common traditional preparations. By the modification of the molecule's carbohydrate moiety or structure a longer duration of erythropoietin receptor stimulation was achieved. The administration of these new molecules (darbepoetin, C.E.R.A.) once or twice a month is also sufficient to achieve serum haemoglobin target levels, making the treatment safer and more comfortable both for the patients and the personnel. These recently developed synthetic erythropoietin receptor stimulating molecules, along with recombinant human erythropoietin, are together called "Erythropoiesis Stimulating Agents". In haemodialysed patients the intravenous route is preferred, but the subcutaneous administration can substantially reduce dose requirements. In praedialysed, transplanted or peritoneally dialysed patients, erythropoiesis stimulating agents should preferably be given subcutaneously both for economic and practical reasons. There are ongoing clinical trials with erythropoiesis stimulating molecules that can be administered by inhalation or per os. Current evidence suggests that the serum haemoglobin level should preferably not exceed 12 g/dl with the use of erythropoiesis stimulating agents. No cardiovascular protective effect of higher serum haemoglobin levels was demonstrated in two large clinical trials. Further well-designed studies are necessary to set evidence-based haemoglobin targets for erythropoiesis stimulating treatment. Arguments for a more widespread use of agents with extended duration include medical, financial and patient satisfaction reasons. The release of new erythropoiesis stimulating agents may further simplify the treatment of renal anaemia.

Topics: Administration, Cutaneous; Administration, Inhalation; Administration, Oral; Anemia; Darbepoetin alfa; Epoetin Alfa; Erythropoiesis; Erythropoietin; Heart Failure; Hematinics; Hemoglobins; Humans; Hypertrophy, Left Ventricular; Infusions, Intravenous; Kidney Failure, Chronic; Receptors, Erythropoietin; Recombinant Proteins; Renal Dialysis

Topics: Anemia; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Multicenter Studies as Topic; Patient Dropouts; Randomized Controlled Trials as Topic; Recombinant Proteins; Research Design

Barriers to the treatment of anemia in patients with chronic kidney disease (CKD), the role of pharmacists in screening patients for anemia and developing guidelines for the use of anemia therapies in patients with CKD, the goals of and considerations in developing pharmacist-managed anemia management clinics, and the potential benefits of these clinics are described.. The complexity of patients with CKD, patient nonadherence to the treatment regimen, a shortage of nephrologists, and a lack of familiarity with clinical practice guidelines and recommendations for treating anemia in these patients are possible barriers to the treatment of anemia. Pharmacists can play a role in improving the treatment of anemia in patients with CKD by screening for anemia, developing guidelines for the use of anemia therapies, and providing patient education to promote adherence to the treatment regimen. The optimal upper limit for hemoglobin concentration during treatment with erythropoietin-stimulating agents (ESA) in patients with CKD remains to be determined, but it should not routinely exceed 13.0 g/dL. Extended dosing of darbepoetin alfa and the new agent continuous erythropoiesis receptor activator appears effective. Iron status often is not assessed in patients with CKD because of difficulty interpreting iron laboratory values and identifying iron deficiency. The usefulness of iron supplementation is not limited to patients with iron deficiency. The intravenous (i.v.) or oral route of administration may be used for iron supplementation in predialysis patients and peritoneal dialysis patients, but the i.v. route is recommended for hemodialysis patients. Adverse effects and drug interactions limit the use of oral iron supplements. Administration of parenteral iron is time consuming and accompanied by concerns about iron accumulation and uncertainty about the optimal maximum serum ferritin concentration. Improved access to care and clinical outcomes and reduced costs have been documented in pharmacist-managed anemia management clinics.. Pharmacists can help overcome barriers to treating anemia in patients with CKD. Clinical and economic benefits are associated with pharmacist-managed anemia management clinics.

Topics: Anemia; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Pharmaceutical Services; Polyethylene Glycols; Recombinant Proteins

The prevalence of chronic kidney disease (CKD) and anemia in the United States, classification scheme for CKD, definition of anemia, etiology and consequences of anemia in patients with CKD, and the clinical and economic benefits of correcting anemia are described.. Approximately 20 million people in the United States population have CKD, and 2-4 million of these may also have anemia, which often goes undetected and untreated. Patients with CKD are now classified into five stages based on the degree of kidney function impairment. Here, anemia is caused by insufficient erythropoietin production, and may occur as early as stage 3 CKD. Potential consequences of anemia include cognitive impairment, angina, and the cardiorenal anemia syndrome, a triad of worsening anemia, worsening CKD, and worsening congestive heart failure. Treatment of anemia in predialysis patients with stage 2-4 CKD may slow renal disease progression and improve energy, work capacity, health-related quality of life, and cardiac function. Optimizing the hemoglobin or hematocrit value before initiating dialysis may reduce mortality. Anemia contributes to significant healthcare costs associated with CKD. Substitution of the subcutaneous route of administration for the intravenous route of administration for epoetin alfa can reduce drug acquisition and healthcare costs, the two largest components of healthcare costs in CKD patients. Efforts to slow the progression of CKD could also have a substantial impact on hospitalizations and costs.. Correcting anemia has the potential to improve clinical and economic outcomes in patients with CKD.

Topics: Anemia; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Kidney Failure, Chronic; Male; Prevalence; Quality of Life; Recombinant Proteins; Renal Dialysis; United States

To compare real-world dosing patterns, drug costs, and hematologic outcome in anemic chronic kidney disease (CKD) patients, not receiving dialysis, who switched from darbepoetin alfa (DARB) to epoetin alfa (EPO) in a community practice setting.. This retrospective observational chart review from a US nephrology clinic included 153 anemic CKD patients > or = 18 years of age who did not receive dialysis during the study period, switched from DARB to EPO between 8/2003 and 8/2005, and received > or = 2 doses of both agents. Paired t-test and McNemar's chi-square were performed comparing pre-switch and post-switch outcomes.. Mean interval between doses increased from 24.3 +/- 11.1 days with DARB to 28.8 +/- 19.8 days with EPO (p = 0.001). Weighted mean pre-switch weekly dose for DARB was 25 mug, while weighted mean post-switch weekly dose for EPO was 7090 Units, resulting in a dose ratio (Units EPO:microg DARB) of 287:1. These doses resulted in mean weekly costs of $110 (DARB) and $86 (EPO). Mean hemoglobin (Hb) levels increased over time from 10.8 g/dL at 6 months pre-switch to 11.1 g/dL 6 months after EPO initiation (p = 0.0132). Mean Hb levels were > 11 g/dL, but below 12 g/dL, while patients received EPO.. Patients switching from DARB to EPO had a greater mean interval between doses, lower drug costs, and consistently maintained recommended Hb levels over time.. The reverse direction (EPO to DARB) was not investigated. Although treatment outcomes were not assessed in a randomized, controlled setting, the study's observational nature provided actual evidence in a real-world setting.

Topics: Aged; Aged, 80 and over; Anemia; Darbepoetin alfa; Drug Administration Schedule; Drug Costs; Epoetin Alfa; Erythropoietin; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Retrospective Studies; Treatment Outcome

Anemia treatment in nondialysis chronic kidney disease (ND-CKD) and dialysis CKD patients (D-CKD) has been recently scrutinized in the literature and by the lay press. New evidence suggests that patients receiving epoetin and achieving higher hemoglobin have a higher risk of death and cardiovascular complications. Data from the Centers for Medicare & Medicaid Services demonstrate upward spiraling costs of injectables, especially epoetin, in the care of CKD patients. There is considerable literature favoring the use of subcutaneous administration of epoetin compared to intravenous route in hemodialysis patients. Evidence clearly shows that the subcutaneous route achieves the target hemoglobin level at a lower administered dose. Thus, the same clinical effect can be achieved at a lower cost. Despite the economic and evidentiary justifications for subcutaneous administration of epoetin, adoption of this strategy has been limited, especially in the United States. Reasons include: inflexibility by dialysis providers because of reduced profitability, claims that patients oppose the subcutaneous route because of pain at the site of injection, concerns regarding pure red cell aplasia associated with subcutaneous administration, and greater hemoglobin cycling with the subcutaneous route. In this article, the advantages and disadvantages of the subcutaneous route are reviewed.

Topics: Anemia; Biological Availability; Diffusion of Innovation; Drug Costs; Epoetin Alfa; Erythropoietin; Evidence-Based Medicine; Half-Life; Hematinics; Hemoglobins; Humans; Injections, Intravenous; Injections, Subcutaneous; Kidney Failure, Chronic; Metabolic Clearance Rate; Nephrology; Patient Selection; Practice Guidelines as Topic; Practice Patterns, Physicians'; Recombinant Proteins; Renal Dialysis; Treatment Outcome; United States

Topics: Anemia; Darbepoetin alfa; Diabetes Mellitus; Epoetin Alfa; Erythropoietin; Heart Failure; Hematinics; Humans; Kidney Failure, Chronic; Recombinant Proteins; Treatment Outcome

Anemia is a frequent complication of chronic kidney disease (CKD). Inadequate production of erythropoietin by the failing kidneys leads to decreased stimulation of the bone marrow to produce red blood cells (RBCs). Anemia of CKD develops early and worsens with progressive renal insufficiency. Although over 40% of patients with CKD are anemic, anemia in this population is under-recognized and undertreated. Of considerable importance, anemia is a risk factor for cardiovascular disease and is associated with higher rates of hospitalization and mortality. Despite the availability of erythropoiesis-stimulating proteins (ESPs) to stimulate RBC production in CKD patients, approximately three fourths of patients initiating dialysis have a hemoglobin <11 g/dL. The recognition of anemia of CKD begins with an estimation of glomerular filtration rate (GFR), which can be far lower than a normal serum creatinine might suggest, especially in the elderly and in those with poor nutrition and muscle mass. If GFR is <60 mL/min/1.73 m(2), hemoglobin should be checked. The anemia is diagnosed when the hemoglobin is <12 g/dL in a man or a postmenopausal woman, or <11 g/dL in a premenopausal woman. The cause of anemia should be investigated in these individuals; this can range from erythropoietin deficiency due to CKD, to deficiency of vitamin B(12) and/or folate, iron deficiency, blood loss, inflammation, malignancy, and aluminum intoxication. After other causes of anemia have been excluded, CKD is the most likely etiology, and it should be treated with an ESP. Currently, epoetin alfa and darbepoetin alfa are the only 2 ESPs approved for use in the United States. Extended dosing of ESP has potential advantages for the patient and may also improve resource utilization. Consequently, both agents have been tested for dosing at extended intervals. Adequate iron stores--defined as transferrin saturation >20% and ferritin >100 mg--as well as ESP administration are needed to produce an appropriate increase in hemoglobin. Poor response to treatment with ESP can be due to many factors, including presence of iron deficiency, inflammation, continued blood loss, and hemoglobinopathy.

Topics: Age Distribution; Aged; Anemia; Causality; Creatine; Darbepoetin alfa; Drug Administration Schedule; Drug Monitoring; Epoetin Alfa; Erythropoietin; Female; Ferritins; Glomerular Filtration Rate; Hematinics; Hemoglobins; Humans; Iron Compounds; Kidney Failure, Chronic; Male; Nutritional Status; Practice Guidelines as Topic; Recombinant Proteins; Risk Factors; Sex Characteristics; Transferrin; Treatment Failure

Improving anemia in patients with chronic renal failure (CRF) and congestive heart failure (CHF) also improves left ventricular hypertrophy (LVH). No previous meta-analyses have been conducted to further examine this association, including the association between LVH and mortality in these patients.. Literature searches on MEDLINE, EMBASE, and OVID were performed using Cochrane Library protocols. Two hundred sixteen abstracts were reviewed preliminarily for inclusion in the meta-analysis of epoetin alfa, anemia and 5 pre-selected parameters of LVH. One hundred seventy-nine abstracts were reviewed for LVH and mortality. The predominant hematologic and left ventricular function changes observed during epoetin alfa treatment in patients with CHF and CRF are (1) increases in hemoglobin (Hb) and hematocrit (Hct); (2) decreases in left ventricular mass (LVM) and LVM index; (3) increase in ejection fraction (EF); and (4) decreases in left ventricular end-diastolic and end-systolic volume. Three independent factors-target Hb, duration of disease, and duration of follow-up-each had a statistically significant association with Hb, Hct, and EF, respectively. A separate meta-analysis using 3 risk models showed LVH is strongly and positively associated with both cardiovascular and all-cause mortality, with two- to three-fold increases in risk.. LVH is common in patients with CRF and CHF. Current findings indicate epoetin alfa therapy results in anemia amelioration, as evidenced by higher Hb and Hct levels, and reduction of key LVH parameters. LVM regression is associated with lower incidence of cardiovascular-related morbidity and mortality, therefore epoetin alfa therapy may provide a survival benefit.

Topics: Adult; Anemia; Epoetin Alfa; Erythropoietin; Female; Heart Failure; Hematinics; Hemoglobins; Humans; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Regression Analysis; Ventricular Function, Left

The number of diabetic patients with renal disease increased significantly in the last years worldwide. Anemia is an important and frequent component of diabetic nephropathy that may begin early in the course of the chronic renal disease of diabetics, and is more severe in diabetic patients with renal disease than in non - diabetic renal patients controlled for the same level of renal function. The reason for the anemia is decreased erythropoietin level caused by diminished production and, in a lesser degree, by increased excretion of erythropoietin in the urine. There is a close connection between diabetic nephropathy, anemia and cardiovascular complications. On the basis of small studies correction of anemia may decrease the progression of diabetic nephropathy and cardiovascular complications. However, the result of ongoing large randomised controlled studies are required to get "evidence-based" data to prove that correction of anemia has beneficial effects on microvascular and macrovascular diabetic complications, particularly cardiac disease, and on progression of diabetic nephropathy.

Topics: Anemia, Hypochromic; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Disease Progression; Epoetin Alfa; Erythropoietin; Heart Failure; Humans; Kidney Failure, Chronic; Randomized Controlled Trials as Topic; Recombinant Proteins; Time Factors

Topics: Anemia; Epoetin Alfa; Erythropoietin; Forecasting; Hematinics; Humans; Kidney Failure, Chronic; Recombinant Proteins; United States

European and US guidelines for renal anaemia management recommend subcutaneous (s.c.) epoetin as the preferred route of administration in pre-dialysis, peritoneal dialysis and haemodialysis patients. However, the restriction of Eprex/Erypro to intravenous (i.v.) administration in Europe has increased the interest of health care professionals regarding the optimal route of administration for all epoetin formulations. There are five major considerations for the 'optimal' route of epoetin administration: efficacy; dosing frequency; convenience; safety and tolerability; and cost. Although epoetin bioavailability is lower after s.c. administration, its efficacy is higher, owing to its prolonged elimination half-life compared with i.v. epoetin. Several studies and clinical surveys comparing s.c. and i.v. administration have demonstrated that equivalent target haemoglobin levels can be maintained at much lower doses of epoetin when administered s.c. Furthermore, s.c. epoetin dosing frequency can be reduced in some patients to once every 2 weeks, without compromising efficacy. Devices such as the Reco-Pen have been specifically designed to facilitate self-administration of s.c. epoetin-beta. An upsurge in the incidence of pure red cell aplasia (PRCA) was linked to the epoetin-alpha product Eprex/Erypo in Europe, and an increase in PRCA cases of the same magnitude was not seen in patients taking other epoetin products s.c. Therefore, PRCA should not be used as an argument against s.c. administration. The reduced dose with s.c. administration of epoetin-beta provides significant cost benefits, without compromising either safety or efficacy, and may also increase patient satisfaction and compliance with treatment.

Topics: Anemia; Drug Administration Schedule; Drug Costs; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Injections, Subcutaneous; Kidney Failure, Chronic; Recombinant Proteins; Red-Cell Aplasia, Pure; Treatment Outcome

The combination of diabetes and chronic kidney disease is associated with increased mortality and reduced quality of life. Recent studies have shown that, in general, late referral of patients to the renal unit increases mortality, and that patients with diabetes who are referred late have a particularly poor prognosis. Several co-morbid conditions have been shown to contribute to poor patient outcomes, including both cardiovascular disease and anaemia. In patients with diabetic nephropathy, anaemia is more severe and is seen earlier than in patients with non-diabetic renal disease. Although the treatment of anaemia with recombinant human erythropoietin (rhEPO; epoetin) is well established, the only data currently available concerning the effects of early intervention in patients with diabetic nephropathy are from small-scale studies. Therefore, two large-scale studies have been designed to provide information on the efficacy of epoetin treatment and on how current management strategies might be improved. The Anaemia CORrection in Diabetes (ACORD) study will provide information on the potential cardiac benefits of early anaemia management in patients with early, type 2 diabetic nephropathy. The Individualised Risk-profiling In DIabEtes Mellitus (IRIDIEM) study will provide evidence-based guidance in risk factor management, by assessing the efficacy of individualized interventions.

Topics: Anemia; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Recombinant Proteins; Referral and Consultation; Survival Rate

Acquired pure red cell aplasia (PRCA) is a rare condition. Traditionally it has been described in association with various etiologies such as parvovirus B19 infection, auto-immune disorders and drugs. Immunologically mediated PRCA is by far the commonest cause in adults, particularly since 1998, when a marked increased incidence of PRCA was noted in chronic renal failure patients receiving subcutaneous (SC) recombinant erythropoietin (rEpo). Typically these patients had been given erythropoietin for correction of anemia of renal failure and subsequently present with severe transfusion dependent anemia. Most cases were associated with SC administration of human serum albumin (HSA) free erythropoieitin alfa product (Eprex). Early recognition and withdrawal of erythropoietin therapy is essential. Treatment with immunosuppressive therapy, particularly in conjunction with renal transplant results in good response with resolution in the majority of cases. The pathogenesis is related to interaction of multiple factors such as formulation change and improper storage leading to increased immunogenicity of the recombinant product. The incidence peaked in 2001 and 2002, subsequently dropping considerably from 2003. This can be explained by the institution of measures such as more stringent handling and storage conditions, improvements in formulation of HSA free Eprex and switch to intravenous (IV) administration for Eprex in dialysis patients. The evidence to date on this condition is summarized in this review.

Topics: Autoimmune Diseases; Epoetin Alfa; Erythropoietin; Humans; Incidence; Kidney Failure, Chronic; Parvoviridae Infections; Parvovirus; Recombinant Proteins; Red-Cell Aplasia, Pure

After 1998, the number of reported cases of pure red cell aplasia (PRCA) increased dramatically among patients with chronic renal failure treated with exogenous erythropoietin, although the incidence of this condition has now abated. Antibody-positive PRCA has been most commonly associated with use of the Eprex brand of epoetin-alpha. ESA (erythropoiesis-stimulating agent)-associated PRCA remains rare, and suspected cases should undergo a thorough diagnostic work-up before laboratory testing for anti-ESA antibody-positive status. This article provides an overview of the recent history and growing understanding of ESA-associated PRCA together with current approaches to the management of this rare side effect of an otherwise valuable therapy.

Topics: Epoetin Alfa; Erythropoietin; Humans; Incidence; Kidney Failure, Chronic; Recombinant Proteins; Red-Cell Aplasia, Pure

Analysis of the biologic effects of erythropoietin and pathophysiology of chronic kidney diseases (CKD) suggests that treatment with erythropoiesis-stimulating agents (ESA) could slow the progression of CKD. By decreasing hypoxia and oxidative stress, it could prevent the development of interstitial fibrosis and the destruction of tubular cells. It could have direct protective effects on tubular cells through its antiapoptotic properties. It could help maintain the integrity of the interstitial capillary network through its effects on endothelial cells. Thus, suggesting that correcting anemia with ESA could slow the progression of CKD is biologically plausible. In patients with CKD, three small prospective studies and a retrospective study have suggested that treatment with ESA may have protective effects. Post-hoc analysis of the Reduction in Endpoints in Noninsulin-dependent Diabetes Mellitus with the Angiotensin II Antagonist Losartan study has also shown that anemia was an independent risk factor for progression of nephropathy in patients with type 2 diabetes. In addition, a large clinical trial, which had to be stopped prematurely because of labeling change for subcutaneous administration of epoetin alfa, suggests that complete normalization of hemoglobin levels is safe in CKD patients not on dialysis and without severe cardiovascular disease. Thus, it seems reasonable to advocate starting a large randomized, prospective study to determine if normalization of hemoglobin concentration can effectively slow the progression of CKD.

Topics: Anemia; Apoptosis; Clinical Trials as Topic; Diabetic Nephropathies; Disease Progression; Epoetin Alfa; Erythrocyte Count; Erythropoietin; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Nephrons; Prospective Studies; Protein Binding; Receptors, Erythropoietin; Recombinant Proteins; Retrospective Studies; Risk Factors

The combination of heart failure and chronic kidney disease (CKD) has received comparatively little attention in terms of clinical research versus investigations of each state individually. It has been known for over a decade that anemia, a cardinal feature of CKD, is associated with higher cardiovascular event rates in late-stage and end-stage renal disease. Although the biological mechanisms linking anemia, renal failure, and heart failure are incompletely understood, more prevalent anemia is consistent in patients with more severe heart failure and is associated with higher mortality rates. Impaired erythropoietin production and resistance to erythropoietin are major contributors to anemia in patients with heart failure. By targeting hemoglobin levels in anemic patients with CKD, through the use of recombinant erythropoietin (epoetin) therapy, it has been hoped that anemia, CKD, and heart failure outcomes can be improved. Darbepoetin alfa was engineered to contain more N-linked carbohydrate chains than erythropoietin, and has an approximately 3 times longer serum half-life. Several clinical trials have addressed the hypothesis that darbepoetin alfa can effectively treat renal anemia at dose frequencies of once per week, or less often, with positive outcomes.

Topics: Anemia; Cardiomyopathies; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Recombinant Proteins

To compare rates of pure red cell aplasia (PRCA) over time in patients with chronic renal failure treated with subcutaneous injections of two brands of epoetin alfa (either Eprex or Epogen) or epoetin beta (NeoRecormon).. Cases of antibody-mediated PRCA associated with epoetin alfa-treated patients were obtained from public databases and company websites and limited to time periods when exposure data also were available The subcutaneous exposure rates per 100 000 patient-years were calculated for the periods 1989-1998 and 1999-2002.. The event rate for antibody-mediated PRCA for Epogen and Eprex were similar from 1989 to 1998, but the number of cases of Eprex-associated PRCA has increased markedly since 1999, even after accounting for subcutaneous exposure. In contrast, rates have remained low for Epogen and NeoRecormon.. The recent increase in PRCA appears to be product specific and cannot be explained solely as a consequence of increased use of the subcutaneous route of administration.

Topics: Epoetin Alfa; Erythropoietin; Humans; Injections, Subcutaneous; Kidney Failure, Chronic; Recombinant Proteins; Red-Cell Aplasia, Pure

Recombinant human erythropoietin (epoetin alfa) has been used in clinical settings for more than a decade. Its indications have expanded considerably from its original use as hormone therapy in the treatment of anemia in adults with chronic kidney disease. Since the introduction of epoetin alfa, a greater understanding of anemia pathophysiology and the interactions of erythropoietin, iron, and erythropoiesis has been elucidated. Anemia is now independently associated with increased mortality and disease progression. Potential survival benefits associated with correction of anemia in various patient populations are leading to consideration of earlier, more aggressive treatment of mild to moderate anemia with epoetin alfa. Moreover, this agent's therapeutic use may extend beyond currently accepted roles. Epoetin alfa is undergoing evaluation with promising results in a variety of new clinical settings, including anemia associated with congestive heart failure, ribavirin-interferon alfa treatment of hepatitis C virus infection, and critical illness. Preclinical studies also have established erythropoietin and its recombinant equivalent to be a pleiotropic cytokine with antiapoptotic activity and neuroprotective actions in the central nervous system. The therapeutic potential of epoetin alfa appears yet to be fully realized.

Topics: Anemia; Clinical Trials as Topic; Cytokines; Epoetin Alfa; Erythropoiesis; Erythropoietin; Heart Failure; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Quality of Life; Recombinant Proteins; United States

Numerous randomized, controlled trials have demonstrated that recombinant human erythropoietin (rHuEPO, epoetin alfa) significantly raises hemoglobin levels, reduces transfusion requirements, and improves quality of life in anemic patients with chronic renal failure. However, this accumulation of data has yet to be systematically examined. The objectives of this meta-analysis were to quantify the effects of epoetin alfa on clinical efficacy, quality of life, hospitalizations, and transfusions by collecting and analyzing the published body of evidence.. Sixteen published studies fulfilled all inclusion criteria and were subjected to data extraction. Data specifically related to hemoglobin and/or hematocrit levels, quality-of-life measurements, number and length of hospitalizations, and number of blood transfusions were then pooled across studies using a random effects meta-analysis. Simple combined estimates of the preselected variables were calculated, and adjusted estimates were made using meta-regression.. Baseline hemoglobin levels (<8 g/dL) increased substantially (40% to 50%) after epoetin alfa administration to a nonanemic state (Hb >11 g/dL) for the pooled study group. Substantial improvements (10% to 70%) were observed for all measures of quality of life. In addition, patients who received epoetin alfa had substantial reductions in hospitalization rate, hospital length of stay, transfusion rate, and number of units transfused.. This meta-analysis strongly suggests that epoetin alfa therapy for patients with chronic renal failure provides important clinical and quality-of-life benefits while substantially reducing hospitalizations and transfusions.

Topics: Anemia; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Recombinant Proteins

The pharmacoeconomics of erythropoietic therapy for the treatment of anemia is receiving renewed attention due to the current availability of two agents. Epoetin alfa has been the standard of therapy for patients with renal disease and cancer-related anemia for more than a decade. Darbepoetin alfa, an alternative agent, is now approved for anemia resulting from renal disease and cancer chemotherapy.. Although direct comparative trials have not been performed with these agents, information published in the last several years regarding their clinical efficacy, safety, and dosing is sufficient, in most cases, to compare costs. With the disclaimer that any efficacy comparison of competing products using published reports has certain limitations, a cost-minimization approach from a provider's perspective was conducted.. To provide background for the economic evaluation, pharmacokinetic and pharmacodynamic data for these two agents are discussed. Recent clinical trials in the nephrology and oncology therapeutic areas are summarized, highlighting study designs, dosing regimens, patient entry criteria, study endpoints, and published results. Cost data, based on average wholesale prices (AWP) in 2003, are compared and calculated from available clinical data with an emphasis on efficacy.. These evaluations largely conclude that epoetin alfa is the better pharmacoeconomic value of the two currently available erythropoietic agents.

Topics: Anemia; Antineoplastic Agents; Cost-Benefit Analysis; Darbepoetin alfa; Dose-Response Relationship, Drug; Economics, Pharmaceutical; Epoetin Alfa; Erythrocytes; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Neoplasms; Recombinant Proteins; Treatment Outcome

Mortality in dialysis patients is greater than that in the general population across all age groups. The disparity in mortality is greatest among patients aged under 35 years. Chronic kidney disease (CKD) is associated with the malnutrition, inflammation and atherosclerosis (MIA) syndrome, which helps to explain the high mortality rates among patients with CKD. Paradoxically, CKD patients exhibit signs of immune suppression as well as immune system activation. Chronic inflammation and immune system activation are not only integral to the MIA syndrome, but also may underlie resistance to erythropoietin treatment in patients with anaemia. Chronic immune system activation is reflected by abnormally raised T-lymphocyte and monocyte expression of both pro- and anti-inflammatory cytokines. Patients who respond well to erythropoietin treatment exhibit fairly normal expression of these cytokines. Patients who persistently fail to respond, however, express abnormally raised levels of the pro-inflammatory cytokines tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma), which are also known to inhibit erythropoiesis. Paradoxically, these patients also express abnormally high levels of the anti-inflammatory cytokines interleukin (IL)-10 and IL-13. Although anti-inflammatory in nature, these cytokines might also affect erythropoiesis. One strategy to overcome the problem of chronic inflammation in anaemic patients with CKD may be treatment with the phosphodiesterase inhibitor, pentoxifylline. Preliminary results suggest that once-daily treatment with 400 mg of pentoxifylline orally not only can reduce T-cell expression of TNF-alpha and IFN-gamma, but can also restore the response to erythropoietin and improve haemoglobin levels. Ongoing studies will investigate further the use of pentoxifylline in erythropoietin resistance.

Topics: CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cytokines; Epoetin Alfa; Erythropoietin; Humans; Inflammation; Interferon-gamma; Interleukins; Kidney Failure, Chronic; Pentoxifylline; Phosphodiesterase Inhibitors; Recombinant Proteins; Renal Dialysis; Treatment Outcome; Tumor Necrosis Factor-alpha

Documentation of anemia-related assessments, interventions, and outcomes is an integral component of proper anemia management for patients with ESRD. In addition to promoting vital communication among medical professionals, documentation helps fulfill regulatory, legal, and payer reimbursement requirements, thereby ensuring that nursing contributions to patient well-being are recognized and that access to care is preserved.

Topics: Anemia; Continuity of Patient Care; Documentation; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Nurse's Role; Physician's Role; Practice Guidelines as Topic; Recombinant Proteins

Novel approaches to anemia associated with cancer and chemotherapy are reviewed. Anemia in cancer patients is usually related to treatment with antineoplastic agents or to the disease itself. The normal concentration of endogenous erythropoietin ranges from 0.1 to 0.2 microU/mL and may increase to 2-10 microU/mL in patients with severe anemia. Many cancer patients with anemia do not have an increase in erythropoietin levels, however. Recombinant human erythropoietin (epoetin alfa), the standard for treating anemia caused by chronic renal failure, is also used to treat cancer chemotherapy-related anemia. It resolves anemia, decreases the need for transfusions, and may improve a patient's quality of life. A newer erythropoiesis-stimulating protein, darbepoetin alfa, was initially evaluated in patients with chronic renal disease. In patients who had never taken epoetin alfa, darbepoetin alfa was able to achieve a hemoglobin concentration of 11 g/dL by four weeks in most patients, and 97% of patients maintained on epoetin alfa were successfully switched to the other drug. Similar positive results were achieved in patients with solid tumors receiving chemotherapy, patients with anemia of chronic disease associated with cancer, and patients with lymphoproliferative malignancies. Darbepoetin alfa has a longer half-life than epoetin alfa, enabling less frequent administration. No difference in toxicity between the two agents has been reported. Epoetin alfa and darbepoetin alfa are effective in the treatment of anemia in patients with cancer.

Topics: Anemia; Antineoplastic Agents; Clinical Trials as Topic; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Half-Life; Humans; Kidney Failure, Chronic; Recombinant Proteins

Anemia of chronic kidney disease (CKD) results primarily from a deficiency of the hormone erythropoietin. Treatment of anemia in the early stages of CKD is essential to reduce the risk of developing anemia-associated complications and to improve health-related quality of life. Treatment with recombinant human erythropoietin (r-HuEPO, epoetin alfa) can correct erythropoietin deficiency and increase red blood cell production, but the short half-life of r-HuEPO necessitates frequent injections. Reducing the frequency of administration has potential benefits for both patients and health care providers. Darbepoetin alfa is a new erythropoietic protein with greater biologic activity and a longer dosing interval than those of r-HuEPO. It has been shown to be effective when administered once/week and once every 2, 3, or 4 weeks, and is well tolerated. With the ability to simplify anemia management by allowing less frequent dosing, darbepoetin alfa offers an effective alternative to r-HuEPO for the treatment of anemia of CKD.

Topics: Anemia; Animals; Clinical Trials as Topic; Darbepoetin alfa; Dose-Response Relationship, Drug; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Injections, Intravenous; Injections, Subcutaneous; Kidney Failure, Chronic; Recombinant Proteins

Recombinant human erythropoietin (r-HuEPO, epoetin alfa), is an established and effective treatment for anemia associated with both chronic kidney disease (CKD) and cancer and has improved the management of anemia over alternatives such as transfusion. Darbepoetin alfa is a new erythropoietic agent with a 3-fold longer half-life and increased in vivo potency relative to r-HuEPO. These properties allow patients to be treated with longer dosing intervals than with r-HuEPO. Relative potency between r-HuEPO and darbepoetin alfa is not a fixed relationship but is dependent on several factors. Clinical study results suggest that greater relative potency differences are seen between r-HuEPO and darbepoetin alfa when the dosing intervals are longer and when r-HuEPO dose requirements are higher. Although 200 U of r-HuEPO contains the same peptide mass as 1 microg of darbepoetin alfa, a fixed ratio of 200:1 does not necessarily predict an appropriate dose conversion between the two drugs across the entire spectrum of dose ranges. When converting patients with CKD from r-HuEPO to darbepoetin alfa, dosing should be based on relevant clinical data. Appropriate guidance for conversion of patients with CKD from r-HuEPO to darbepoetin alfa is provided in the approved United States package insert for darbepoetin alfa. In patients who are prescribed darbepoetin alfa, either by conversion from r-HuEPO or as de novo treatment, therapy should begin according to recommendations in the package insert, after which, doses should be titrated individually according to each patient's hemoglobin response. Dosing data from oncology clinical studies, although not necessarily applicable to CKD, indicate similar potency ratios between r-HuEPO and darbepoetin alfa, and in addition affirm the finding that, as the interval between doses of darbepoetin alfa is increased, hemoglobin response is maintained.

Topics: Anemia; Clinical Trials as Topic; Darbepoetin alfa; Drug Administration Schedule; Drug Labeling; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Injections, Intravenous; Kidney Failure, Chronic; Neoplasms; Recombinant Proteins; Therapeutic Equivalency

The National Kidney Foundation's Kidney Disease Outcomes Quality Initiative recommends a target hemoglobin (Hb) level of 11 to 12 g/dL (hematocrit [Hct] of 33% to 36%) for both peritoneal dialysis and hemodialysis patients. However, national tracking data indicate that peritoneal dialysis patients have consistently lower Hb/Hct levels. This article focuses on anemia management challenges that are unique to the peritoneal dialysis population. Nursing knowledge and management of Epoetin alfa dosing and administration techniques, peritonitis and other infections, and iron supplementation may help improve anemia-related outcomes in peritoneal dialysis patients.

Topics: Adult; Anemia, Iron-Deficiency; Drug Monitoring; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hematocrit; Hemoglobins; Humans; Iron Compounds; Kidney Failure, Chronic; Male; Middle Aged; Patient Compliance; Peritoneal Dialysis; Recombinant Proteins; Total Quality Management

Topics: Adaptation, Physiological; Anemia; Cardiovascular System; Cognition Disorders; Drug Costs; Epoetin Alfa; Erythropoietin; Exercise; Heart Failure; Hematocrit; Hemodynamics; Hemoglobins; Humans; Hypertrophy, Left Ventricular; Iron; Kidney Failure, Chronic; Multicenter Studies as Topic; Practice Guidelines as Topic; Quality of Life; Randomized Controlled Trials as Topic; Recombinant Proteins; Reference Values; Renal Dialysis; Risk; Thrombophilia; Treatment Outcome

Topics: Adult; Aged; Anemia; Child; Comorbidity; Drug Costs; Epoetin Alfa; Erythropoietin; Female; Hematocrit; Hemoglobins; Humans; Iron; Kidney Failure, Chronic; Male; Middle Aged; Multicenter Studies as Topic; Myocardial Infarction; Occupations; Peritoneal Dialysis; Physical Fitness; Practice Guidelines as Topic; Quality of Life; Randomized Controlled Trials as Topic; Recombinant Proteins; Reference Values; Renal Dialysis; Thrombophilia; Treatment Outcome

Topics: Anemia; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Neoplasms; Recombinant Proteins

Stimulation of red blood cell precursors by Epoetin alfa results in a predictable, dose-dependent increase in red blood cell mass. Iron is an important substrate that supports red blood cell and hemoglobin development. Patients who receive Epoetin alfa therapy typically require intravenous iron supplementation to ensure proper red cell formation. Target and ceiling iron levels should be determined on the basis of safety considerations, the predicted clinical response, and individual patient replacement needs. Nurses can use clinical parameters such as body weight, baseline and target hemoglobin values, and iron losses from blood and other sources to estimate iron replacement doses, thereby providing a guide for appropriate iron replacement.

Topics: Anemia, Iron-Deficiency; Body Weight; Dose-Response Relationship, Drug; Drug Monitoring; Drug Therapy, Combination; Epoetin Alfa; Erythrocyte Indices; Erythropoiesis; Erythropoietin; Ferritins; Hematinics; Hematocrit; Hemoglobins; Humans; Infusions, Intravenous; Iron Compounds; Iron Overload; Kidney Failure, Chronic; Nurse's Role; Nursing Assessment; Recombinant Proteins; Renal Dialysis; Safety Management; Transferrin

A wide variety of prescribed and over-the-counter (OTC) agents can affect the production or viability of red blood cells, thereby contributing to anemia. An apparent hyporesponse to Epoetin alfa therapy in end-stage renal disease (ESRD) patients can sometimes be traced to a medication prescribed to treat a comorbid condition. The anemic potential of many of these agents has been defined and can often be anticipated or avoided by examining and modifying the regimen. Nurses can help assess and prevent medicine-related hyporesponse to Epoetin alfa by obtaining thorough histories and providing ongoing counseling on the need to minimize exposure to substances that contribute to anemia. A case study is provided to illustrate the use of nursing assessment skills to identify potential drug-related hyporesponse to Epoetin alfa.

Topics: Anemia; Angiotensin-Converting Enzyme Inhibitors; Education, Nursing, Continuing; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis

Anemia is equally devastating in children as in adults. Decreased energy levels from anemia can lead to deterioration in the ability to (a) exercise, (b) participate in the normal activities of childhood, and (c) learn. Moreover, these effects may make it difficult for children to engage in social interactions with their peers, thereby altering their development. Epoetin alfa therapy effectively ameliorates the anemia of end-stage renal disease in pediatric dialysis patients and thus minimizes many of these negative effects. This article examines the use of Epoetin alfa in the pediatric population, including the role of nurses in educating patients and ensuring prescribed outcomes.

Topics: Adolescent; Age Factors; Anemia, Iron-Deficiency; Child; Energy Metabolism; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Kidney Failure, Chronic; Patient Education as Topic; Play and Playthings; Recombinant Proteins; Renal Dialysis; Treatment Outcome

Epoetin alfa is the cornerstone of anemia therapy in patients with end-stage renal disease. In addition to stimulating erythropoiesis, Epoetin alfa has been demonstrated to affect hemostasis. Such effects may be important because patients with chronic renal failure have a bleeding diathesis that is multifactorial in origin. Therefore, a computer literature search on the relationship between Epoetin alfa therapy for anemia in patients with end-stage renal disease and platelets, coagulation, coagulation inhibitors, and fibrinolysis was performed. All articles and abstracts reporting original data in the English language on Epoetin alfa and its effect on hemostasis were reviewed. The literature suggests that the effects of Epoetin alfa on the coagulation cascade are of minimal clinical importance. However, Epoetin alfa transiently increases the number of circulating platelets and improves platelet function, and these effects are associated with a return of the bleeding time towards normal.

Topics: Anemia; Epoetin Alfa; Erythropoietin; Fibrinolysis; Hematinics; Hemostasis; Humans; Kidney Failure, Chronic; Recombinant Proteins

Improving patient outcomes by achieving a stable Hct in the higher end of the target Hct range of 30% to 36% is the primary goal of anemia management and Epoetin alfa therapy. Recently, attention has been focused on the potential differences between subcutaneous (s.c.) and intravenous (i.v.) administration. Although some patients may require less Epoetin alfa when it is administered by the s.c. route, many patients require the same dose or more due to the significant heterogeneity in response. To ensure that therapeutic outcomes are maintained or improved, clinicians should evaluate both staff considerations and individual patient tolerance and response when determining the optimal route of administration.

Topics: Anemia; Education, Nursing, Continuing; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins

Clinical evidence indicates that maintaining a stable hematocrit (Hct) higher in the target range of 30% to 36% can lead to improvement in overall patient outcomes. On the basis of these data, a recent analysis by the Dialysis Outcomes Quality Initiative Anemia Work Group has recommended a target Hct of 33% to 36% (hemoglobin 11 g/dl to 12 g/dl). Maintaining a stable Hct higher in the target range provides nurses and other dialysis clinicians with two benefits: improved patient care and decreased time and costs for patient management. This article focuses on the data supporting such a policy. Clinical practices from two prominent dialysis centers are presented as models of good anemia management.

Topics: Anemia; Body Weight; Epoetin Alfa; Erythropoietin; Health Status; Hematinics; Hematocrit; Humans; Kidney Failure, Chronic; Patient Care Planning; Recombinant Proteins; Survival Analysis

Anemia is one of the most common complications of Chronic Kidney Disease (CKD). The vast majority of Egyptian CKD patients are interchangeably treated with Darbepoetin Alfa (DPA) and Epoetin Alfa (EPA) to achieve and maintain target hemoglobin levels. Our study aimed to compare the efficacy and safety of DPA versus EPA for managing anemia amongst Egyptian patients with CKD undergoing dialysis.. A multicenter, open label, randomized, prospective, parallel study was conducted. Patients with CKD undergoing dialysis with Hb level < 10 g/dl were enrolled. The primary efficacy endpoint was the change in hemoglobin concentration at the evaluation period (weeks 20-24). Prespecified adverse events of interest following administration, including blood transfusions requirement, blood pressure and hemoglobin excursions, the relationship between C - Reactive Protein (CRP) and hemoglobin, were assessed.. Only 98 of 104 enrolled patients completed the study, fifty patients received EPA, and 48 patients received DPA. Our results showed that a significantly higher percentage of patients who achieved target Hb level ≥ 11 g/dL in DPA treated group vs. EPA as well as the meantime to achieve Hb level ≥ 10 g/dL was shorter in DPA treated group. Safety profiles of both treatments were similar. A negative correlation was observed between serum CRP and hemoglobin level in hemodialysis patients.. Our study showed that DPA was more effective and well tolerated in achieving and maintaining Hb levels with lower dosing frequency compared to EPA. Furthermore, CRP is recommended to be routinely measured where patients with higher CRP require high ESA doses.

Topics: Anemia; Darbepoetin alfa; Egypt; Epoetin Alfa; Erythropoietin; Hemoglobins; Humans; Kidney Failure, Chronic; Prospective Studies; Recombinant Proteins; Renal Dialysis; Renal Insufficiency, Chronic

EPREX®/ERYPO®/PROCRIT® (epoetin alfa, Janssen-Cilag GmbH) was the first available recombinant human erythropoietin (rHuEPO) and was universally reference product as per the recommendation provided by European Medicines Agency. EPIAO® is a biosimilar formulation of EPREX®, and making it a 1:1 dose conversion from EPREX® according to recommendation of European Medicines Agency. This study evaluated the clinical efficacy and safety of EPIAO® in subjects with end-stage renal disease receiving hemodialysis after intravenous administration.. This study was a multicenter, prospective, randomized, double-blind, parallel-group, 2-cohort, maintenance phase, therapeutic equivalence study to evaluate a 1:1 dose conversion from EPREX® to EPIAO® in terms of clinical efficacy and safety that was conducted at 20 sites in 2 countries in patients with end-stage renal disease on hemodialysis. Eligible subjects were treated with EPREX® (reference product of epoetin) for a period of at least 3 months before the treatment period, and then were randomly assigned to the group of EPREX® or EPIAO®. Primary endpoints were mean absolute change in hemoglobin level and mean absolute change in weekly epoetin dosage from baseline to 6 months after treatment with EPIAO®/EPREX® in parallel groups.. A total of 200 people received the random intervention and were included in the safety set. After 6, 9, and 12 months of treatment with EPIAO® or EPREX®, there were no significant differences in the hemoglobin levels of the 2 groups compared with baseline. The 95% confidence interval for the treatment difference was within the predetermined acceptable range: ±0.5 g/dL. There were no significant differences in the epoetin dosage of the 2 groups compared with the baseline. The 95% confidence interval for the treatment difference was within the predetermined acceptable range: ± 45 IU/kg. There were no significant differences in the incidence of adverse events between the EPIAO® and EPREX® groups. Most adverse events were mild to moderate and were reverted/resolved.. EPIAO® demonstrated promising effectiveness and manageable safety in patients with end-stage renal disease on hemodialysis.

Topics: Anemia; Biosimilar Pharmaceuticals; Epoetin Alfa; Erythropoietin; Hemoglobins; Humans; Kidney Failure, Chronic; Prospective Studies; Renal Dialysis; Translocation, Genetic; Treatment Outcome

Erythropoietin stimulating agent (ESA) has been standard of care in treating renal anaemia for the past 20 years. Many patients have limited access to ESA in view of long-term costs leading to suboptimal ESA dosage. Biosimilar epoetin is a potential cost-effective alternative to originator for optimal renal anaemia management.. To determine efficacy and safety of PDA10 in treating renal anaemia in haemodialysis patients, in comparison to the originator epoetin-α, Eprex®.. A phase 3, multicentre, multi-national, double-blind, randomised, active-controlled and parallel group study conducted over 40 weeks in Malaysia and Korea. End stage kidney disease patients undergoing regular haemodialysis who were on erythropoietin treatment were recruited. The study has 3 phases, which included a 12-week titration phase, followed by 28-week double-blind treatment phase and 24-week open-label extension phase.. The PDA10 and Eprex® were shown to be therapeutically equivalent (p < 0.0001) with mean absolute change in haemoglobin from baseline of - 0.176 (± 0.91) g/dl and - 0.118 (± 1.114) g/dl, respectively. Weekly dose change was 10.01 IU/kg/week in PDA10 group and 10.30 IU/kg/week in Eprex® group, which has no significant difference. There were no significant differences in the safety profile between PDA10 and Eprex® groups.. This study has confirmed the therapeutic equivalence between PDA10 and Eprex® in terms of efficacy, dosage requirement and safety profile in haemodialysis patients with renal anaemia.. The study was registered with the National Medical Research Register ( NMRR-13-400-16313 ). This study has been registered retrospectively with Clinical Research Information Service ( CRiS ), Republic of Korea on 25 March 2021.

Topics: Adult; Aged; Anemia; Double-Blind Method; Epoetin Alfa; Female; Hematinics; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Treatment Outcome

We evaluated the efficacy and safety of roxadustat versus epoetin alfa for the treatment of chronic kidney disease-related anemia in patients new to dialysis.. HIMALAYAS was a Phase 3, open-label, epoetin alfa-controlled trial. Eligible adults were incident to hemodialysis/peritoneal dialysis for 2 weeks to ≤4 months prior to randomization and had mean hemoglobin (Hb) ≤10.0 g/dL. Primary endpoints were mean Hb (g/dL) change from baseline averaged over Weeks 28-52 regardless of rescue therapy [non-inferiority criterion: lower limit of 95% confidence interval (CI) for treatment difference >-0.75] and percentage of patients achieving an Hb response between Weeks 1 and 24 censored for rescue therapy (non-inferiority margin for between-group difference -15%). Adverse events were monitored.. The intent-to-treat population included patients randomized to roxadustat (n = 522) or epoetin alfa (n = 521). Mean (standard deviation) Hb changes from baseline averaged over Weeks 28-52 were 2.57 (1.27) and 2.36 (1.21) in the roxadustat and epoetin alfa groups. Roxadustat was non-inferior [least squares mean difference: 0.18 (95% CI 0.08, 0.29)] to epoetin alfa. Percentages of patients with an Hb response were 88.2% and 84.4% in the roxadustat and epoetin alfa groups, respectively. Roxadustat was non-inferior to epoetin alfa [treatment-group difference 3.5% (95% CI -0.7%, 7.7%)]. Adverse event rates were comparable between treatment groups.. Roxadustat was efficacious for correcting and maintaining Hb levels compared with epoetin alfa. Roxadustat had an acceptable safety profile.

Topics: Anemia; Epoetin Alfa; Erythropoietin; Glycine; Hematinics; Hemoglobins; Humans; Isoquinolines; Kidney Failure, Chronic; Recombinant Proteins; Renal Dialysis

This is a post-hoc analysis evaluating erythropoiesis stimulating agents' (ESA) related costs while using an additional ultrafilter (Estorclean PLUS) to produce ultrapure dialysis water located within the fluid pathway after the treatment with reverse osmosis and before the dialysis machine. Twenty-nine patients (19 treated with epoetin alfa and 10 with darboepoetin alfa) were included in the analysis. We showed to gain savings of 210 € per patient (35 € per patient each month) with epoetin alfa during the experimental period of 6 months, compared to the control period and of 545 € per patient (90 € per patient each month) with darboepoetin alfa. Estorclean PLUS had a cost of 600 € (25 € per month per each patient) and was used for 6 months. Intravenous iron therapy with sodium ferrigluconate had a cost of 0,545 €/62,5 mg. In conclusion, during the experimental period with the use of Estorclean, we obtained global savings of 11 € per patient per month with epoetin alfa and 30 € per patient per month with darboepoetin alfa to treat anemia in dialysis patients.

Topics: Aged; Aged, 80 and over; Anemia; Cost Savings; Costs and Cost Analysis; Cross-Over Studies; Darbepoetin alfa; Distillation; Epoetin Alfa; Female; Ferric Compounds; Filtration; Hematinics; Hemodialysis Solutions; Hemoglobins; Humans; Inflammation; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Water

This study was conducted to compare the safety and efficacy of intravenous epoetin alfa-epbx, an epoetin alfa biosimilar, to epoetin alfa in patients on hemodialysis with ESKD and anemia.. In this 24-week, multicenter, double-blind comparative efficacy and safety study, 612 patients on hemodialysis with ESKD and anemia who had stable hemoglobin and were receiving stable doses of intravenous epoetin alfa were randomized (1:1) to intravenous epoetin alfa or epoetin alfa-epbx. Dosing was adjusted according to the epoetin alfa prescribing information. The coprimary efficacy end points were the least squares mean difference between the two treatments in mean weekly hemoglobin level and mean weekly epoetin dose per kilogram of body weight during the last 4 weeks of treatment.. The least squares mean difference between epoetin alfa-epbx and epoetin alfa in weekly hemoglobin was -0.12 g/dl and the 95% confidence interval (-0.25 to 0.01) was contained within the prespecified equivalence margin (-0.5 to 0.5 g/dl). The least squares mean difference between epoetin alfa-epbx and epoetin alfa in weekly epoetin dose per kilogram of body weight was 0.37 U/kg per week, and the 95% confidence interval (-10.40 to 11.13) was contained within the prespecified equivalence margin (-45 to 45 U/kg per week). Incidences of adverse events (77.1% versus 75.3%), serious adverse events (24.9% versus 27.0%), and deaths (. This 24-week, comparative, clinical trial in patients on hemodialysis with ESKD and anemia demonstrated there is no clinically meaningful difference in efficacy or safety between epoetin alfa-epbx and epoetin alfa.

Topics: Administration, Intravenous; Anemia; Biosimilar Pharmaceuticals; Double-Blind Method; Epoetin Alfa; Female; Hematinics; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis

For patients with anemia undergoing hemodialysis, erythropoiesis-stimulating agents (ESAs) are typically dosed via precise algorithms. Using one such algorithm, we assessed the maintenance of hemoglobin levels in patients switched from epoetin alfa reference product (Epogen®) to epoetin alfa-epbx (RetacritTM; a biosimilar to US-licensed Epogen®/Procrit®).. This randomized, open-label, non-inferiority study was conducted at Fresenius Medical Care North America (FMCNA) hemodialysis centers. Patients with anemia and chronic kidney disease undergoing maintenance hemodialysis and receiving routine intravenous (IV) Epogen® were randomized 1: 1 to switch to IV RetacritTM or continue standard-of-care (Epogen®) for 24 weeks, using analogous versions of the FMCNA ESA-dosing algorithm. The primary endpoint was the proportion of time patients' hemoglobin was 9-11 g/dL during weeks 17-24.. Of 432 randomized patients, 418 received treatment (RetacritTM, n = 212; standard-of-care, n = 206) and comprised the full analysis set. A similar proportion of patients discontinued from each arm. The proportion of time patients' hemoglobin was within the target range was 61.9% (95% CI 57.5-66.2) in the RetacritTM arm and 63.3% (95% CI 58.7-67.7) in the standard-of-care arm. The difference in proportions between treatment arms was -1.4% (95% CI -7.6 to 4.9), and the lower bound of the confidence interval was within the pre-specified non-inferiority margin of -12.5%. There was no statistically significant difference between arms in the mean change from baseline in the weekly mean ESA dose during weeks 17-24, and no clinically relevant differences in safety outcomes.. Switching to RetacritTM was non-inferior to continuing -Epogen® in maintaining hemoglobin levels in patients receiving hemodialysis, when both ESAs were dosed using a specified algorithm (ClinicalTrials.gov, NCT02504294).

Topics: Adult; Aged; Aged, 80 and over; Algorithms; Anemia; Biosimilar Pharmaceuticals; Dose-Response Relationship, Drug; Drug Dosage Calculations; Drug Substitution; Epoetin Alfa; Female; Hematinics; Hemoglobins; Humans; Injections, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Retrospective Studies; Treatment Outcome; Young Adult

Anemia is one of the most prevalent complications in patients with chronic kidney disease, which is believed to be caused by the insufficient synthesis of erythropoietin by the kidney. This phase III study aimed to compare the efficacy and safety of CinnaPoietin® (epoetin beta, CinnaGen) with Eprex® (epoetin alfa, Janssen Cilag) in the treatment of anemia in ESRD hemodialysis patients.. In this randomized, active-controlled, double-blind, parallel, and non-inferiority trial, patients were randomized to receive either CinnaPoietin® or Eprex® for a 26-week period. The primary endpoints of this study were to assess the mean hemoglobin (Hb) change during the last 4 weeks of treatment from baseline along with the evaluation of the mean weekly epoetin dosage per kilogram of body weight that was necessary to maintain the Hb level within 10-12 g/dL during the last 4 weeks of treatment. As the secondary objective, safety was assessed along with other efficacy endpoints.. A total of 156 patients were included in this clinical trial. There was no statistically significant difference between treatment groups regarding the mean Hb change (p = 0.21). In addition, the mean weekly epoetin dosage per kg of body weight for maintaining the Hb level within 10-12 g/dL showed no statistically significant difference between treatment arms (p = 0.63). Moreover, both products had comparable safety profiles. However, the incidence of Hb levels above 13 g/dL was significantly lower in the CinnaPoietin® group.. CinnaPoietin® was proved to be non-inferior to Eprex® in the treatment of anemia in ESRD hemodialysis patients. The trial was registered in Clinicaltrials.gov (NCT03408639).

Topics: Adult; Aged; Anemia; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Injections, Subcutaneous; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Renal Dialysis; Treatment Outcome

HX575 (biosimilar epoetin alfa) was approved in Europe in 2007 for the treatment of chronic kidney disease (CKD)-related anemia. This study assessed the clinical equivalence of HX575 with the US-licensed reference epoetin alfa (Epogen®/Procrit®, Amgen/Janssen) following subcutaneous (SC) administration in dialysis patients with CKD-related anemia.. This randomized, double-blind, parallel-group, multicenter study (NCT01693029) was conducted at 49 US clinical sites. Eligible patients were aged ≥18 years, had end-stage renal disease, were on hemodialysis or peritoneal dialysis for ≥6 months (or ≥12 months in the case of a failed kidney transplant), and were receiving treatment with stable SC doses of epoetin alfa. Eligible patients also had mean hemoglobin (Hb) concentration between 9.0 and 11.5 g/dL during the screening period. The primary endpoint was the mean absolute change in Hb concentration between the screening/baseline period (week-4 to week-1) and the evaluation period (weeks 21 to 28).. Hb values at the end of the evaluation period and the Hb change from baseline to evaluation period were similar between treatment groups. The estimated difference between groups in mean absolute change in Hb concentration was -0.093 g/dL, with 90% CI (-0.23 to 0.04) entirely within the pre-specified equivalence limits (-0.5 to 0.5 g/dL). The safety profile of each medicine was similar and as expected in dialysis patients, and neither method of treatment led to the development of neutralizing, clinically relevant antibodies.. SC HX575 in dialysis patients with renal anemia was therapeutically equivalent to the reference medicine in terms of maintaining stable Hb levels and safety.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Biosimilar Pharmaceuticals; Double-Blind Method; Epoetin Alfa; Female; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Therapeutic Equivalency; Treatment Outcome; United States; Young Adult

Hemodialysis (HD) patients often show impaired response to erythropoiesis-stimulating agents (ESAs). Extended HD membrane permeability may potentially improve ESA response.. Twenty-four prevalent HD patients were randomly assigned to 12 weeks use of high cut-off (HCO) membrane (in every second dialysis treatment) or continued treatment with high-flux membrane. We monitored changes in hemoglobin (Hb), ESA dose, and key biochemical markers.. The Hb level increased in the study group (from 11.6 ± 1.0 to 12.5 ± 1.5 g/dl; p = 0.038) but was stable in the control group. Variation over time in ESA dose and ESA resistance index did not differ between groups. HCO membrane usage for 12 weeks led to decreased hepcidin level, from 303 ± 189 to 157 ± 83 ng/ml (p = 0.024); serum albumin level decreased and stabilized 15 ± 6% below baseline.. These results indicate that use of a more permeable dialysis membrane may improve ESA responsiveness in iron-replete HD patients. Extensive albumin removal may preclude long-term use of the HCO membrane.

Topics: Aged; Anemia; C-Reactive Protein; Drug Resistance; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Hepcidins; Humans; Interleukin-6; Kidney Failure, Chronic; Male; Membranes, Artificial; Middle Aged; Permeability; Pilot Projects; Recombinant Proteins; Renal Dialysis; Serum Albumin

Roxadustat (FG-4592) is an oral hypoxia-inducible factor prolyl-hydroxylase inhibitor that promotes erythropoiesis through increasing endogenous erythropoietin, improving iron regulation, and reducing hepcidin.. Phase 2, randomized (3:1), open-label, active-comparator, safety and efficacy study.. Patients with stable end-stage renal disease treated with hemodialysis who previously had hemoglobin (Hb) levels maintained with epoetin alfa.. Part 1: 6-week dose-ranging study in 54 individuals of thrice-weekly oral roxadustat doses versus continuation of intravenous epoetin alfa. Part 2: 19-week treatment in 90 individuals in 6 cohorts with various starting doses and adjustment rules (1.0-2.0mg/kg or tiered weight based) in individuals with a range of epoetin alfa responsiveness. Intravenous iron was prohibited.. Primary end point was Hb level response, defined as end-of-treatment Hb level change (ΔHb) of -0.5g/dL or greater from baseline (part 1) and as mean Hb level ≥ 11.0g/dL during the last 4 treatment weeks (part 2).. Hepcidin, iron parameters, cholesterol, and plasma erythropoietin (the latter in a subset).. Baseline epoetin alfa doses were 138.3±51.3 (SD) and 136.3±47.7U/kg/wk in part 1 and 152.8±80.6 and 173.4±83.7U/kg/wk in part 2, in individuals randomly assigned to roxadustat and epoetin alfa, respectively. Hb level responder rates in part 1 were 79% in pooled roxadustat 1.5 to 2.0mg/kg compared to 33% in the epoetin alfa control arm (P=0.03). Hepcidin level reduction was greater at roxadustat 2.0mg/kg versus epoetin alfa (P<0.05). In part 2, the average roxadustat dose requirement for Hb level maintenance was ∼1.7mg/kg. The least-squares-mean ΔHb in roxadustat-treated individuals was comparable to that in epoetin alfa-treated individuals (about -0.5g/dL) and the least-squares-mean difference in ΔHb between both treatment arms was -0.03 (95% CI, -0.39 to 0.33) g/dL (mixed effect model-repeated measure). Roxadustat significantly reduced mean total cholesterol levels, not observed with epoetin alfa. No safety concerns were raised.. Short treatment duration and small sample size.. In this phase 2 study of anemia therapy in patients with end-stage renal disease on maintenance hemodialysis therapy, roxadustat was well tolerated and effectively maintained Hb levels.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Epoetin Alfa; Female; Glycine; Hematinics; Humans; Isoquinolines; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Time Factors; Treatment Outcome; Young Adult

In hemodialysis (HD) patients, zinc depletion caused by inadequate intake, malabsorption, and removal by HD treatment leads to erythropoiesis-stimulating agent (ESA) hyporesponsiveness. This study investigated the effects of zinc supplementation in HD patients with zinc deficiency on changes in the erythropoietin responsiveness index (ERI).. Patients on HD with low serum zinc levels (<65 μg/dL) were randomly assigned to two groups: The polaprezinc group (who received daily polaprezinc, containing 34 mg/day of zinc) (n = 35) and the control group (no supplementation) (n = 35) for 12 months. All the 70 patients had been taking epoetin alpha as treatment for renal anemia. ERI was measured with the following equation: Weekly ESA dose (units)/dry weight (kg)/hemoglobin (g/dL).. There were no significant changes in hemoglobin levels within groups or between the control and polaprezinc groups during the study period. Although reticulocyte counts were increased immediately after zinc supplementation, this change was transient. Serum zinc levels were significantly increased and serum copper levels were significantly decreased in the polaprezinc group after three months; this persisted throughout the study period. Although there was no significant change in the serum iron or transferrin saturation levels in the polaprezinc group during the study period, serum ferritin levels significantly decreased following polaprezinc treatment. Further, in the polaprezinc group, ESA dosage and ERI were significantly decreased at 10 months and nine months, respectively, as compared with the baseline value. Multiple stepwise regression analysis revealed that the change in the serum zinc level was an independent predictor of lowered ERI.. Zinc supplementation reduces ERI in patients undergoing HD and may be a novel therapeutic strategy for patients with renal anemia and low serum zinc levels.

Topics: Administration, Oral; Aged; Anemia; Carnosine; Copper; Dietary Supplements; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Female; Ferritins; Hemoglobins; Humans; Iron; Kidney Failure, Chronic; Male; Middle Aged; Multivariate Analysis; Organometallic Compounds; Regression Analysis; Renal Dialysis; Trace Elements; Zinc; Zinc Compounds

Randomized trials found that use of erythropoiesis-stimulating agents to target normal hematocrit (Hct) levels (>39%) compared with 27%-34.5% increases cardiovascular risk and mortality among chronic kidney disease patients. However, the effects of the most widely used Hct target in the past 2 decades, 34.5%-39%, have never been examined.. To compare the effects of 2 Hct target strategies-30.0%-34.5% (low) and 34.5%-39.0% (mid) in a high-risk population: elderly dialysis patients with significant comorbidities.. Observational data from the US Renal Data System were used to emulate a randomized trial in which patients were assigned to either Hct strategy. Follow-up started after completing 3 months of hemodialysis and ended 6 months later. We conducted the observational analogs of intention-to-treat and per-protocol analyses. Inverse-probability weighting was used to adjust for measured time-dependent confounding by indication.. A total of 22,474 elderly patients with both diabetes and cardiovascular disease who initiated hemodialysis in 2006-2008.. Hazard ratios (HRs) and survival probabilities for all-cause mortality and a composite cardiovascular and mortality endpoint.. The intention-to-treat HR (95% confidence interval) for mid versus low Hct strategy was 1.05 (0.99-1.11) for all-cause mortality and 1.03 (0.98-1.08) for the composite endpoint. The per-protocol HR (95% confidence interval) for mid versus low Hct strategy was 0.98 (0.78-1.24) for all-cause mortality and 1.00 (0.81-1.24) for the composite outcome.. Among hemodialysis patients, we did not find differences in 6-month survival or cardiovascular risk between clinical strategies that target Hct at 30.0%-34.5% versus 34.5%-39.0%.

Topics: Aged; Anemia, Iron-Deficiency; Cardiovascular Diseases; Comorbidity; Dose-Response Relationship, Drug; Drug Dosage Calculations; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Kidney Failure, Chronic; Male; Recombinant Proteins; Renal Dialysis; Risk Factors; Survival Analysis; Treatment Outcome; United States

Indoxyl sulfate (IS) suppresses erythropoietin (EPO) activity and exerts renal damage. The oral adsorbent AST-120 reduces IS load and has antioxidant and renoprotective properties; however, its roles in the treatment of anemia remain unclear in chronic kidney disease (CKD) patients.. Fifty-one Stage 5 predialysis CKD patients with hemoglobin <10 g/dL were randomly assigned to receive two period treatments with AST-120 plus once-monthly administration of continuous EPO receptor activator (CERA, A) and CERA alone (B), with a 4-week washout period in between. Mean changes of serum creatinine, estimated glomerular filtration rate (eGFR) and hemoglobin levels from the baseline were compared between two treatments.. The baseline and postintervention mean creatinine levels were 5.48 and 5.36 mg/dL in the Treatment A, and 5.14 mg/dL and 5.61 g/dL in the Treatment B group, respectively (treatment effect P = 0.025, period effect P = 0.467, carryover effect P = 0.384). The baseline and postintervention mean hemoglobin levels were 9.27 and 10.47 g/dL in the Treatment A, and 9.63 g/dL and 9.54 g/dL in the Treatment B group, respectively (treatment effect P = 0.039, period effect P = 0.001, carryover effect P = 0.060). Use of AST-120 significantly reduced IS and p-cresyl sulfate (PCS) levels. Hierarchical regression showed that eGFR was an independent predictor for hemoglobin after adjustment of serum free IS and PCS levels (B = 0.049, P = 0.005).. Use of adjuvant AST-120 may improve renal function and hemoglobin levels than use of CERA alone in late-stage CKD patients. The change of eGFR might play an intermediate role between serum IS/PCS and improve hemoglobin levels. The finding offered insight into novel therapeutic strategies of anemia for late-stage CKD patients.

Topics: Adult; Aged; Anemia; Carbon; Cross-Over Studies; Drug Synergism; Epoetin Alfa; Erythropoietin; Female; Hemoglobins; Humans; Indican; Kidney; Kidney Failure, Chronic; Male; Microspheres; Middle Aged; Oxides; Polyethylene Glycols; Recombinant Proteins

To study the specific features of diastolic dysfunction (DD) in different types of left ventricular (LV) hypertrophy (LVH) in patients with end-stage renal failure (ESRF) and to estimate the cardioprotective effect of erythropoietin.. 107 patients (57 women and 50 men) aged 22 to 63 years with ESRF were examined. The follow-up was 18 months. LV ejection fraction, peak early diastolic filling rate, peak late diastolic filling rate, their ratio, LV isovolumic relaxation time, LV end-diastolic diameter, LV end-diastolic volume, LV end-diastolic diameter index (EDDI), LV posterior wall and ventricular septal thickness, and LV mass index were determined. J. Gottdiener's classification based on the calculation of EDDI and LV relative wall thickness was used to estimate LV geometry. Erythropoietin was given to patients with the baseline level of hemoglobin (Hb) < 110 g/l or hematocrit (Ht) < 33%; and iron (III) hydroxide sucrose complex was used to those with ferritin < 100 microg/l or transferrin saturation < 20%. The target level of blood pressure was 130/80 mm Hg; Hb was less than 110 g/l for women and 120 g/l for men; Ht, > 33%.. The patients with ESRF were found to have different types of DD and LVH, the severity of which correlated with the magnitude of renal anemia and arterial hypertension (AH). Adequate correction of anemia and AH promoted the transition of more to less severe DD and LVH and in a number of cases the recovery of LV structure and function.. ESRF is characterized by different types of DD, which are pathogenetically closely related to different types of LVH. Adequate correction of renal anemia and AH may cause a significant reduction and, in a number of cases, alleviate VLH, and normalize LV systolic and diastolic functional values.

Topics: Adult; Cardiotonic Agents; Diastole; Echocardiography; Epoetin Alfa; Erythropoietin; Female; Humans; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Treatment Outcome; Ventricular Function, Left; Young Adult

To evaluate the safety and efficacy of epoetin alfa administered in extended-dosing intervals to a target hemoglobin (Hb) level not exceeding 12.0 g/dL for the treatment of anemia in subjects with chronic kidney disease (CKD) not on dialysis.. An open-label, randomized, multicenter, controlled study consisting of a 1-week screening phase and a 26-week open-label treatment phase.. Twenty-seven long term care (LTC) facilities in the United States.. Subjects with CKD who were not receiving dialysis, who had not received an erythropoiesis-stimulating agent for 8 weeks before screening, and whose Hb levels were lower than 11.0 g/dL at screening were eligible.. In the epoetin alfa group, subjects were administered 20,000 international units epoetin alfa subcutaneously every 2 weeks (Q2W). Dosing was based on the Hb concentration measurement obtained by HemoCue Hb201+System (Quest Diagnostics; Madison, NJ) at the time of the scheduled dose. When the Hb concentration was 11.0 to 11.5 g/dL on 2 consecutive biweekly measurements, the dose was doubled and administered on the day that the second consecutive measurement was obtained. The dosing interval was then extended to every 4 weeks (Q4W). Subjects in the standard of care (SOC) group received treatment for their anemia according to the practice of the LTC facility.. Study visits were every 2 weeks, at which time blood was drawn and used for efficacy analysis. Measurements included: the Hb concentration change from baseline to the end of the study; the proportion of subjects who achieved an Hb response (defined as 2 consecutive Hb measurements at least 1.0 g/dL greater than baseline or 2 consecutive Hb measurements ≥11.0 g/dL at any time during the study); the time to the Hb response; the proportion of subjects who received a transfusion and the number of units of transfused; the proportion of epoetin alfa-treated subjects converting to Q4W dosing; and the proportion of subjects who converted to Q4W dosing and remained on Q4W dosing through the end of the study.. A total of 157 subjects were randomized: 118 subjects to the epoetin alfa group and 39 to the SOC group. The mean change in Hb was significantly greater in the epoetin alfa group (0.9 g/dL) compared with the SOC group (0.3 g/dL) (P = .006). A significantly greater percentage of subjects achieved a Hb response in the epoetin alfa group (85.1%) compared with the SOC group (53.8%) (P < .001). The time to achieve a Hb response was significantly shorter in the epoetin alfa group (41 days) than in the SOC group (114 days) (P < .0001). There were no transfusions in the SOC group, whereas 4 subjects (3.5%) required transfusions in the epoetin alfa group. Of the 114 subjects receiving epoetin alfa, 33 (28.9%) subjects were converted to Q4W dosing, and all subjects who converted were able to be maintained on this schedule.. The administration of epoetin alfa in extended-dosing intervals of Q2W followed by Q4W was safe and effective in the treatment of anemia in subjects with CKD who reside in LTC facilities.

Topics: Aged; Aged, 80 and over; Anemia; Drug-Related Side Effects and Adverse Reactions; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Long-Term Care; Male; Outcome Assessment, Health Care; Recombinant Proteins; Residential Facilities; United States

Reticuloendothelial blockade in hemodialysis patients prevents optimal intravenous (IV) iron utilization. Vitamin C has emerged as a potential therapy to improve anemia treatment by enhancing iron mobilization. However, Vitamin C can act as a pro-oxidant in the presence of iron. This was a prospective, open-label, crossover study. Thirteen patients with end-stage renal disease on hemodialysis and four healthy controls were assigned to receive 100 mg of IV iron sucrose (IS) or 100 mg of IV IS co-administered with 300 mg of IV Vitamin C (IS + C) in random sequence. Serum samples for IL-1, IL-6, TNF-α and IL-10 and non-transferrin bound iron were obtained at baseline, 45 min and 105 min post study medication administration. Peripheral blood mononuclear cells were isolated at the same time points and stained with fluorescent probes to identify intracellular reactive oxygen species and mitochondrial membrane potential (Δψm) by flow cytometry. Lipid peroxidation was assessed by plasma F2-isoprosatane concentration. Both IS and IS + C were associated with increased plasma F2-isoprostanes concentrations post-infusion. Maximal plasma F2-isoprostane concentrations after IS + C were significantly elevated from baseline (234 ± 0.04 vs. 0.198 ± 0.028 ng/mL, p = 0.02). After IS + C, IL-1, IL-6, IL-10, and TNF-alpha were significantly elevated compared to baseline. After IS alone only IL-6 was noted to be elevated. Intracellular production of H(2)O(2) and loss of mitochondrial membrane potential (Δψm) was observed after IS while IS + C was associated with increased O (2) (·-) production. Both IS and IS + C induced serum cytokine activation accompanied by lipid peroxidation, however, IS + C induced higher plasma concentrations of F2-isoprostanes, IL-1, IL-10, and TNF-α post-infusion. Long-term safety studies of IV iron co-administered with Vitamin C are warranted.

Topics: Adult; Ascorbic Acid; Cross-Over Studies; Cytokines; Epoetin Alfa; Erythropoietin; F2-Isoprostanes; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Lipid Peroxidation; Male; Membrane Potential, Mitochondrial; Middle Aged; Oxidative Stress; Prospective Studies; Reactive Oxygen Species; Recombinant Proteins; Systems Biology

We investigated the long-term effects of maintaining high hemoglobin (Hb) on renal function in patients with chronic kidney disease not on dialysis. Subjects (Hb < 10 g/dL and serum creatinine (Cr) 2-6 mg/dL) were randomized to either a high Hb group (N = 161, 11.0 ≤ Hb < 13.0 g/dL) receiving darbepoetin alfa or to a low Hb group (N = 160, 9.0 ≤ Hb < 11.0 g/dL) with epoetin alfa, stratified according to baseline Hb and serum Cr levels, comorbidity of diabetes, and study centers. Primary endpoints were composites of the following events: doubling of serum Cr, initiation of dialysis, renal transplantation, or death. Three-year cumulative renal survival rates (95% CI) were 39.9% (30.7-49.1%) and 32.4% (24.0-40.8%) in the high and low Hb groups, respectively (log-rank test; P = 0.111). A Cox proportional-hazards model adjusted by age, sex and the randomization factors showed a significantly lower event rate in the high Hb group (P = 0.035). The estimated hazard ratio (95% CI) for the high versus the low Hb group was 0.71 (0.52-0.98), the risk reduction was 29% in the high Hb group. Incidences of serious adverse cardiovascular events did not differ significantly between the high and low Hb groups (3.1% and 4.4%, respectively). No safety issues were noted in either group. Maintaining higher Hb levels with darbepoetin alfa better preserved renal function in patients with chronic kidney disease not on dialysis.

Topics: Aged; Creatinine; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Incidence; Kidney Failure, Chronic; Kidney Function Tests; Male; Middle Aged; Proportional Hazards Models; Recombinant Proteins; Treatment Outcome

Anemia is common among patients with chronic kidney disease (CKD). The introduction of erythropoietin treatment has changed anemia management, but the therapeutic hemoglobin (Hb) target is still under debate, and clinical evidence for its effect on cardiac functions and QOL is sparse.. A 16-week dose-response study and a 32-week follow-Up study were combined. After correcting anemia of less than 10 g/dl in pre-dialysis Japanese CKD patients, a higher Hb target (12-13 g/dl) by darbepoetin alfa (DPO) was compared with the conventional Hb target by epoetin alfa (EPO). Outcomes were anemia correction, management of the left ventricular mass index (LVMI) and QOL scores.. No significant difference was seen in Hb at baseline and week 16, but a significant difference was recorded at week 34 (12.34 +/- 0.93 g/dl for DPO and 10.43 +/- 0.90 g/dl for EPO). In both groups, LVMI decreased similarly until week 16, but the decrease of EPO was retarded, and a significant difference between LVMI was seen only in DPO at week 34 (100.7 +/- 16.6 g/m(2) for DPO and 110.9 +/- 25.2 g/m(2) for EPO). Relationships between Hb and LVMI change at week 34 were examined by stratifying Hb into four groups (Hb <10 g/dl, 10 g/dl < or = Hb <11 g/dl, 11 g/dl < or = Hb <12 g/dl and 12 g/dl < or = Hb), and a decrease of LVMI was prominent in the 12 g/dl < or = Hb group. Correction of anemia to 11 g/dl or more led to improved QOL scores. No safety difference was observed among the treatments.. Targeting a higher Hb around 12 g/dl was more beneficial than targeting conventional Hb in terms of reduction of LVMI and QOL. Further studies to determine the appropriate Hb target are necessary.

Topics: Adult; Aged; Asian People; Darbepoetin alfa; Dose-Response Relationship, Drug; Drug-Related Side Effects and Adverse Reactions; Epoetin Alfa; Erythropoietin; Female; Follow-Up Studies; Heart Ventricles; Hemoglobins; Humans; Hypertrophy, Left Ventricular; Japan; Kidney Failure, Chronic; Male; Middle Aged; Quality of Life; Recombinant Proteins

The primary objective of the trial was to prove the therapeutic equivalence of epoetin zeta to epoetin alfa when administered subcutaneously for maintaining target hemoglobin (Hb) in patients with renal anemia on chronic hemodialysis. Additional information was provided on the safety and tolerability of epoetin zeta with particular focus on the formation of anti-erythropoietin antibodies.. A total of 462 patients were randomized to either epoetin zeta or alfa for 28 weeks after an open period of dose adjustment of 12-16 weeks with only epoetin zeta. The aim of treatment was to maintain Hb between 10.0-12.0 g/dL with constant epoetin dosage. Primary endpoints were the mean Hb level and the mean weekly epoetin dosage during the last 4 weeks of treatment. Safety endpoints were the occurrence of anti-erythropoietin antibodies, incidence of Hb levels above 13 g/dL, ratings of tolerability, and adverse events (AEs).. The mean Hb level (+/-SD) during the last 4 weeks of treatment was 10.94+/-0.84 g/dL (epoetin zeta) and 11.02+/-0.94 g/dL (epoetin alfa). The 95% confidence interval (CI) (''C0.28 g/dL to 0.12 g/dL) was entirely within the predefined equivalence range (+/-0.5 g/dL). The mean weekly epoetin dosage per body weight over the last 4 weeks of treatment was 97.0+/-94.3 IU/kg/week (epoetin zeta) and 86.0+/-78.0 IU/kg/week (epoetin alfa). The 95% CI (''C8.06 IU/kg/week to 29.96 IU/kg/week) was also within the predefined equivalence range of +/-45 IU/kg/week. The most common AEs were infections and infestations (15.1% of patients on epoetin zeta and 14.8% of patients on epoetin alfa). None of the patients developed anti-erythropoietin antibodies.. Epoetin zeta, administered subcutaneously, is equivalent to epoetin alfa in respect of its clinical efficacy. The safety profile of both products is similar: no unexpected AEs were observed, no patients developed anti-erythropoietin antibodies, and both epoetin preparations were well tolerated.

Topics: Adult; Aged; Anemia; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Injections, Subcutaneous; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Single-Blind Method; Therapeutic Equivalency

Anemia is an early sign of chronic kidney dysfunction, caused by many different factors, but the insufficient erythropoietin synthesis is the crucial factor in its development.. The objective of our study was to compare effectiveness of epoietin alpha and beta application in the treatment of renal anemia in chronic hemodialyzed patients.. The group included 60 patients of both sexes, randomly chosen. Criteria for including patients into the study were: older than 18 years, haemodialyzed longer than three months and treated by epoietin beta, stable level of hemoglobin, between 9 and 11 g/dL at least two successive measurements and no malignant disease present. The patients were then randomized into groups: 20 patients were administered epoietin alpha intravenously instead of epoietin beta subcutaneously (experimental group); 20 patients were administered intravenously epoietin beta instead of epoietin beta subcutaneously (control group A), the rest of 20 patients were administered epoietin beta subcutaneously (control group B). All the testees were administered epoietin alpha or beta three times weekly after haemodialysis, intravenously or subcutaneously.. Comparison among mean values of hematological and biochemical parameters before starting the treatment by erythropoietin, and third and sixth months after therapy in the studied groups, no significant difference was found (p > 0.05).. Epoietin alpha and beta showed approximate degree of efficacy in renal anemia treatment of hemodialysis patients. The way of erythropoetin administration did not significantly effect the level of hemoglobin and hematocrit in six months research period.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Injections, Intravenous; Injections, Subcutaneous; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Treatment Outcome

Anemia is a risk factor for death, adverse cardiovascular outcomes and poor quality of life in patients with chronic kidney disease (CKD). Erythropoietin Stimulating Agents (ESA) are commonly used to increase hemoglobin levels in this population. In observational studies, higher hemoglobin levels (around 11-13 g/dL) are associated with improved survival and quality of life compared to hemoglobin levels around 9-10 g/dL. A systematic review of randomized trials found that targeting higher hemoglobin levels with ESA causes an increased risk of adverse vascular outcomes. It is possible, but has never been formally tested in a randomized trial, that ESA dose rather than targeted hemoglobin concentration itself mediates the increased risk of adverse vascular outcomes. The Clinical Evaluation of the DOSe of Erythropoietins (C.E. DOSE) trial will assess the benefits and harms of a high versus a low fixed ESA dose for the management of anemia in patients with end stage kidney disease.. This is a randomized, prospective open label blinded end-point (PROBE) trial due to enrol 2204 hemodialysis patients in Italy. Patients will be randomized 1:1 to 4000 IU/week versus 18000 IU/week of intravenous epoietin alfa or beta, or any other ESA in equivalent doses. The dose will be adjusted only if hemoglobin levels fall outside the 9.5-12.5 g/dL range. The primary outcome will be a composite of all-cause mortality, non fatal stroke, non fatal myocardial infarction and hospitalization for cardiovascular causes. Quality of life and costs will also be assessed.. The C.E.DOSE study will help inform the optimal therapeutic strategy for the management of anemia of hemodialysis patients, improving clinical outcomes, quality of life and costs, by ascertaining the potential benefits and harms of different fixed ESA doses.. Clinicaltrials.gov NCT00827021.

Topics: Adult; Anemia; Cardiovascular Diseases; Cost-Benefit Analysis; Epoetin Alfa; Erythropoietin; Female; Health Care Costs; Hematinics; Hemoglobins; Hospitalization; Humans; Kidney Failure, Chronic; Male; Outcome Assessment, Health Care; Quality of Life; Recombinant Proteins; Renal Dialysis

Treatment of anaemia in renal-insufficient patients relies on the use of an erythropoiesis-stimulating agent (ESA). This study aimed to compare the impact of two different strategies of ESA prescribing on variation in haemoglobin (Hb) concentration in end-stage renal disease (ESRD) patients.. Patients with ESRD, on haemodialysis, and who had received ESA for >3 months were recruited. Different parameters were analysed: demographics, Hb level the last day of the year before dialysis, the most recent weekly ESA dose, risk factors for resistance and cost. Each institution continued its local practice for achieving the desired Hb level: increasing the ESA dose to overcome resistance in one centre and defining an upper ESA-dose limit in the other.. A total of 185 patients were recruited. No significant differences in the biological parameters were found between the two populations. In both centres, Hb levels were comparable and mean levels exceeded 11 g/dL, despite the higher ESA doses given in one centre to achieve this target. This finding also held true for the subgroups with greater than or equal to two resistance factors. These two strategies led to large between-centre differences in treatment costs.. The ESA-use strategy difference probably indicates that erythropoietin-resistance was not overcome with increased dosing. The Hb concentrations remained stable even when ESA doses were increased. On current evidence, the cheaper ESA-dose limitation strategy is preferable but randomized controlled studies, including comparisons of alternative ESA formulations are necessary.

Topics: Aged; Anemia; Darbepoetin alfa; Dose-Response Relationship, Drug; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; France; Hematinics; Humans; Inpatients; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Retrospective Studies; Treatment Outcome

The effects of different hemoglobin targets when using erythropoiesis-stimulating agents on quality of life are somewhat controversial, and predictors of change in quality of life in endstage renal disease have not been well characterized.. Five hundred ninety-six incident hemodialysis patients without symptomatic cardiac disease were randomly assigned to hemoglobin targets of 9.5 to 11.5 g/dl or 13.5 to 14.5 g/dl for 96 weeks, using epoetin_alfa as primary therapy. Patients and attending physicians were masked to treatment assignment. Quality of life, a secondary outcome, was prospectively recorded using the Kidney Disease Quality of Life (KDQoL) questionnaire at weeks 0, 24, 36, 48, 60, 72, 84, and 96, with prespecified outcomes being fatigue and quality of social interaction.. The mean age and prior duration of dialysis therapy of the study population were 50.8 and 0.8 yr. Mortality was low, reflecting the relatively healthy group enrolled. Of 20 domains within the KDQoL only the prespecified domain of fatigue showed significant change over time between the two groups. Improvement in fatigue scores in the high-target group ranged from 3.2 to 7.9 over time (P = 0.007) compared with change in the low-target group. Higher body mass index and lower erythropoietin dose at baseline were independent predictors of improvement in multiple KDQoL domains.. In relatively healthy hemodialysis patients, normal hemoglobin targets may have beneficial effects on fatigue. Improvement in multiple domains of quality of life is associated with higher body mass index and lower erythropoietin requirements.

Topics: Anemia; Body Mass Index; Canada; Epoetin Alfa; Erythropoietin; Europe; Fatigue; Female; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Quality of Life; Recombinant Proteins; Renal Dialysis; Social Behavior; Surveys and Questionnaires; Time Factors; Treatment Outcome

PDpoietin is a recombinant erythropoietin alfa that has been introduced by a manufacturer in Iran. We assessed the effectiveness and complications of PDpoietin in comparison with Eprex in anemic patients on hemodialysis.. This clinical trial was performed in a multicenter setting. Patients with a hemoglobin level less than 12 g/dL were assigned into 2 groups in order to receive either Eprex (Janssen Cilag) or PDpoietin (Pooyesh Darou) for 3 months.. Forty-one and 34 patients completed the study in the PDpoietin and Eprex groups, respectively. The mean hemoglobin levels at baseline were not significantly different between the two groups of patients with PDpoietin and Eprex. In both groups, hemoglobin levels increased significantly, but there were no significant differences between the two groups at months 1, 2, and 3. At the end of the study, the mean hemoglobin levels reached 11.6 +/- 1.7 g/dL and 11.8 +/- 1.9 g/dL, respectively (P = .002; P = .01). The mean hemoglobin per cumulative of drug dose index (hemoglobin/[erythropoietin dose/1000 x injections per month]) was not significantly different between the two groups at different treatment stages, and it did not change significantly in each group during the course of the study. No serious complications were reported.. Eprex and PDpoietin could equally increase the hemoglobin levels with no significant complication. Therefore, PD can be used for treatment of anemia in patients on dialysis, and the patients will have the advantages of its availability and low price.

Topics: Adult; Aged; Anemia; Cost-Benefit Analysis; Drug Costs; Epoetin Alfa; Erythropoietin; Feeding Behavior; Female; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis

In clinical practice, physicians often use once-weekly (QW) and biweekly (Q2W) dosing of epoetin alfa to treat anemia in patients with chronic kidney disease (CKD). Although the literature supports this practice, previous studies were limited by short treatment duration, lack of randomization, or absence of the approved three times per week (TIW) dosing arm. This randomized trial evaluated extended dosing regimens of epoetin alfa, comparing QW and Q2W to TIW dosing in anemic CKD subjects. The primary objective was to show that treatment with epoetin alfa at QW and Q2W intervals was not inferior to TIW dosing.. 375 subjects with stage 3 to 4 CKD were randomized equally to the three groups and treated for 44 wk; to explore the impact of changing from TIW to QW administration on hemoglobin (Hb) control and adverse events, subjects on TIW switched to QW after 22 wk. The Hb was measured weekly, and the dose of epoetin alfa was adjusted to achieve and maintain an Hb level of 11.0 to 11.9 g/dl.. Both the QW and Q2W regimens met the primary efficacy endpoint. More subjects in the TIW group than in the QW and Q2W groups exceeded the Hb ceiling. Adverse events were similar across treatment groups and consistent with the morbidities of CKD patients.. Administration of epoetin alfa at QW and Q2W intervals are potential alternatives to TIW dosing for the treatment of anemia in stage 3 to 4 CKD subjects.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Dose-Response Relationship, Drug; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Hypertension, Renal; Incidence; Iron; Kidney Failure, Chronic; Male; Middle Aged; Morbidity; Recombinant Proteins; Renal Dialysis; Thromboembolism; Treatment Outcome

The recombinant human epoetin-a HX575 (Sandoz Pharmaceuticals GmbH/Hexal AG, Holzkirchen, Germany) is the first biosimilar erythropoiesis-stimulating agent (ESA) with marketing authorization in Europe. The primary objective of the study was the evaluation of therapeutic equivalence in terms of hemoglobin (Hb) response of HX575 compared with the comparator product (EPREX/ ERYPO, Janssen-Cilag/Ortho Biotech, Neuss, Germany) in the long-term intravenous (i.v.) treatment of anemia in chronic renal failure patients on hemodialysis following a 1 : 1 dose conversion from the comparator product to HX575.. Hemodialysis patients with Hb levels of 10.0 - 13.0 g/dl were randomized to either continue their current i.v. epoetin-a treatment or switch to HX575. During treatment, epoetin dosages were titrated to maintain Hb values. The primary endpoint was the difference between treatment groups in the mean absolute change of Hb levels between baseline and evaluation period (Weeks 25 - 28).. Therapeutic equivalence of HX575 and the comparator epoetin-alpha, assessed during the evaluation period, was statistically confirmed: mean changes in Hb levels were 0.15 +/- 0.09 g/dl in the HX575 and 0.06 +/- 0.12 g/dl in the comparator epoetin-a group, with a difference between groups of 0.08 g/dl (95% confidence interval: -0.17; 0.34). Hb levels and epoetin dosages remained stable throughout the entire study period of 56 weeks. The long-term safety profile of HX575 was similar to that of the comparator epoetin-alpha. No antibody formation was detected.. The study demonstrated therapeutic equivalence of biosimilar HX575 to the comparator epoetin-a, together with a comparable safety profile.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Double-Blind Method; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Therapeutic Equivalency; Young Adult

Polymorphonuclear leukocyte priming and low grade inflammation are related to severity of kidney disease. Erythropoietin-receptor is present on PMNLs. OBJECTIVESxi: To evaluate the effect of 20 weeks of epoetin-alpha treatment on PMNL characteristics in relation to the rate of kidney function deterioration in patients with chronic kidney disease.. Forty anemic chronic kidney disease patients, stage 4-5, were assigned to EPO and non-EPO treatment for 20 weeks. A group of 20 healthy controls was also studied. PMNL priming and PMNL-derived low grade inflammation were estimated, in vivo and ex vivo, before and after EPO treatment: The rate of superoxide release, white blood cells and PMNL counts, serum alkaline phosphatase and PMNL viability were measured. EPO-receptor on PMNLs was assayed by flow cytometry. The effect of 20 weeks of EPO treatment on kidney function was related to the estimated glomerular filtration rate. esults: EPO treatment attenuated superoxide release ex vivo and in vivo and promoted PMNL survival ex vivo. Decreased low grade inflammation was reflected by reduced WBC and PMNL counts and ALP activity following treatment. EPO retarded the deterioration in GFR. The percent of PMNLs expressing EPO-R was higher before EPO treatment and correlated positively with the rate of superoxide release. After 20 weeks of EPO treatment the percent of PMNLs expressing EPO-R was down-regulated.. These non-erythropoietic properties of EPO are mediated by EPO-R on PMNLs, not related to the anemia correction. A new renal protection effect of EPO via attenuation of PMNL priming that decreases systemic low grade inflammation and oxidative stress is suggested.

Topics: Aged; Anemia; Epoetin Alfa; Erythropoietin; Female; Glomerular Filtration Rate; Hematinics; Humans; Kidney Failure, Chronic; Male; Neutrophils; Oxidative Stress; Receptors, Erythropoietin; Recombinant Proteins; Severity of Illness Index; Superoxide Dismutase

The aim of this trial was to gather data on the long-term safety of a new erythropoietin preparation (epoetin zeta), focusing on the formation of anti-erythropoietin antibodies, when administered intravenously for maintenance of target hemoglobin concentration in anemic patients with end-stage renal failure receiving chronic hemodialysis. In addition, we aimed to provide information on the efficacy of epoetin zeta under open, noncontrolled conditions.. Patients received epoetin zeta intravenously, 1-3 times/week for 56 weeks (overall patient group, n=745) or 108 weeks (Bulgarian subgroup, n=164). The aim of treatment was to maintain hemoglobin values between 10.5 and 12.5 g/dL with constant epoetin dosage. Primary (safety) endpoints were the occurrence of anti-erythropoietin antibodies and the evaluation of adverse events (AEs). Secondary (efficacy) endpoints included the mean weekly dose of epoetin per kg of body weight and mean hemoglobin concentrations.. No patients developed neutralizing anti-erythropoietin antibodies. The most commonly reported AEs were infections and infestations (34.1%); followed by injury, poisoning, and procedural complications (25.8%); and gastrointestinal disorders (21.9%); 37.3% of patients reported serious AEs. The hemoglobin values remained stable, with mean values after 56 weeks of 11.3-11.6 g/dL for the overall group and 11.1-11.6 g/dL for the Bulgarian subgroup. The dosage of epoetin zeta was stable throughout the course of the trial. No cases of lack of (or loss of ) efficacy were observed in the course of the trial.. The evaluation of the primary endpoints provided data supporting the intravenous administration of epoetin zeta in patients with chronic renal failure. Neutralizing antibodies against erythropoietin were not detected, and there were no reports of patients with increasing erythropoietin resistance. Our results suggest that intravenous administration of epoetin zeta is effective regarding its ability to maintain stabilized hemoglobin levels within the target range of 10.5-12.5 g/dL.

Topics: Anemia; Blood Transfusion; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Male; Recombinant Proteins; Renal Dialysis

This Phase III study examined the efficacy and safety of C.E.R.A., a continuous erythropoietin receptor activator, given once every 2 weeks (Q2W) via subcutaneous or intravenous injection using pre-filled syringes, for maintaining hemoglobin (Hb) levels in patients with chronic kidney disease (CKD) on dialysis who converted directly from epoetin therapy.. Patients (n = 336) were randomized 1:1 to continue epoetin at their current dose, route and administration interval (once to three times weekly (QW-TIW)), or receive C.E.R.A. Q2W by the same route as previous epoetin treatment for 36 weeks. Dosage was adjusted to maintain patients' Hb within +/-1.0 g/dl of baseline value and within 10.0-13.5 g/dl. Primary endpoint was mean change in Hb between baseline and the evaluation period (weeks 29-36).. Mean change in Hb for C.E.R.A. and epoetin was 0.088 and -0.030 g/dl, respectively (endpoint Hb 11.93 and 11.86 g/dl, respectively). Analysis showed that C.E.R.A. was as effective as epoetin in maintaining Hb (p < 0.0001), and was well tolerated. The administration route had no impact on primary endpoint.. Q2W C.E.R.A. administered using pre-filled syringes effectively maintains stable control of Hb in patients on dialysis who convert directly from epoetin QW-TIW.

Topics: Adult; Aged; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Hemoglobins; Humans; Injections, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Polyethylene Glycols; Recombinant Proteins; Renal Dialysis; Syringes; Treatment Outcome

Confounding-by-indication is a bias in nonexperimental studies that occurs when outcomes are compared for treated and untreated patients and the treatment or medication dose is related to predictors of the outcome. Two recent publications reported that greater epoetin alfa (EPO) doses were associated with increased mortality rates. We assessed whether confounding-by-indication might account for these results.. We used a retrospective cohort study design.. Hemodialysis patients were randomly selected from a large dialysis organization from July 2000 to June 2002 and were required to have completed a 9-month baseline period.. EPO dose assessed during months 7 to 9 of the baseline period and monthly throughout the follow-up period. Hemoglobin (Hb) was assessed as average value during months 4 to 6 of the baseline period and monthly throughout the follow-up period. All other covariates were assessed during months 1 to 6 of the baseline period.. All-cause mortality during the 1 year of follow-up. Baseline Cox models were fitted with log EPO and Hb with and without adjustment for baseline patient characteristics. Time-dependent models were fitted with time-varying log EPO and Hb and, separately, lagged log EPO and Hb, with adjustment for baseline patient characteristics.. 22,955 patients met our inclusion criteria. In the unadjusted model, we observed increased mortality risk with increasing EPO dose (hazard ratio [HR], 1.31 per log unit increase; 95% confidence interval [CI], 1.26 to 1.36). Adjustment for baseline patient characteristics resulted in an appreciably decreased HR (HR, 1.21; 95% CI, 1.15 to 1.28). In the lagged time-dependent analyses, estimates ranged from HR of 0.93 (95% CI, 0.92 to 0.95) to HR of 1.01 (95% CI, 0.99 to 1.03) for the 1- and 2-month lagged models, respectively.. This analysis was limited to prevalent hemodialysis patients, and inhospital EPO dosing information was unavailable.. The observed mortality risk estimates associated with EPO dose in nonexperimental studies in dialysis patients may be highly sensitive to the analytic method used. This highlights the complexity of evaluating the association between EPO dose, Hb level, and mortality in these studies.

Topics: Adult; Aged; Cohort Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Follow-Up Studies; Humans; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Retrospective Studies

To evaluate the therapeutic efficacy and safety of epoetin zeta, compared with epoetin alfa, in maintaining target haemoglobin (Hb) concentrations in patients with anaemia and chronic kidney disease (CKD) maintained on haemodialysis.. Patients received epoetin zeta or epoetin alfa intravenously, 1-3 times/week for 12 weeks, then the alternative treatment for 12 weeks, in this double-blind, crossover, phase III trial. Eligible patients were 18-75 years old with CKD stage 5 maintained on haemodialysis. Patients had received epoetin for > or = 3 months upon study entry and had achieved a target Hb level of 10.5-12.5 g/dL with a stable epoetin dose.. Primary efficacy endpoints were intra-individual differences (test-reference) in mean Hb levels and mean weekly dose/kg of body weight. Safety endpoints included occurrence of neutralizing anti-erythro poietin antibodies, tolerability, and adverse events (AEs).. In total, 313 patients were randomized to receive epoetin zeta (n = 155) or epoetin alfa (n = 158); 146 and 145 patients (respectively) switched treatment after 12 weeks. Mean (range) Hb levels were 11.35 (8.96-14.22) g/dL and 11.54 (8.74-13.84) g/dL for patients receiving epoetin zeta and epoetin alfa, respectively (95% confidence interval [CI] [test-reference]: 0.09-0.28 g/dL, within the predefined equivalence range of +/-0.6 g/dL). Mean (range) weekly doses were 92.68 (12.74-398.41) IU/kg/wk and 92.58 (10.53-393.07) IU/kg/wk for patients receiving epoetin zeta and epoetin alfa, respectively (95% CI [test-reference]: -4.67 and 4.29 IU/kg/wk, within the equivalence range of +/-45.00 IU/kg/wk). Patients underwent minor nominal dose adjustments during treatment crossover. AE profile was similar for both products; the most commonly reported AEs were infections and infestations (in 26.5% of patients receiving epoetin zeta and 23.6% receiving epoetin alfa). No patients developed neutralizing anti-erythropoietin antibodies.. Epoetin zeta is therapeutically equivalent to epoetin alfa in the maintenance of target Hb levels in patients with renal anaemia. No unexpected AEs were seen.

Topics: Adult; Aged; Anemia; Cross-Over Studies; Double-Blind Method; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hematocrit; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Therapeutic Equivalency

To assess the therapeutic equivalence of epoetin zeta and epoetin alpha for correction of haemoglobin (Hb) concentration in patients with anaemia and chronic kidney disease (CKD) stage 5 maintained on haemodialysis.. In total, 609 patients with CKD and anaemia (Hb < 9 g/dL) were randomly assigned to receive either epoetin zeta or epoetin alpha intravenously, one to three times per week for 24 weeks. Dosing was titrated individually to achieve a stable, target Hb concentration of 11-12 g/dL. Primary endpoints were the mean weekly dose of epoetin per kilogram of body weight and mean Hb concentration during the last 4 weeks of treatment. Safety endpoints were the occurrence of anti-erythropoietin antibodies, ratings of tolerability and adverse events (AEs).. Mean (+/- standard deviation [SD]) Hb concentration over the last 4 weeks of treatment was 11.61 +/- 1.27 g/dL for patients receiving epoetin zeta, compared with 11.63 +/- 1.37 g/dL for patients receiving epoetin alpha (95% confidence interval [CI]: -0.25 to 0.20 g/dL). Mean (+/- SD) epoetin zeta weekly dose over the last 4 weeks of treatment was 182.20 +/- 118.11 IU/kg/wk, compared with 166.14 +/- 109.85 IU/kg/wk for epoetin alpha (95% CI: -3.21 to 35.34 IU/kg/wk). The most commonly reported AEs (> 5% of patients) were infections and infestations (12.5% and 12.8% of patients treated with epoetin zeta and epoetin alpha, respectively) and vascular disorders (8.5% and 8.9%, respectively). No patients developed neutralizing anti-erythropoietin antibodies.. Epoetin zeta, administered intravenously, is therapeutically equivalent to epoetin alpha in the correction of low Hb concentration in patients with CKD undergoing haemodialysis. No unexpected AEs were seen and both epoetin zeta and epoetin alpha were well tolerated.

Topics: Adolescent; Adult; Aged; Anemia; Confidence Intervals; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Follow-Up Studies; Hemoglobins; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Risk Assessment; Severity of Illness Index; Therapeutic Equivalency; Treatment Outcome

In patients with chronic renal failure, the ability to reduce the administration frequency of subcutaneous (SC) erythropoietin (epoetin) could provide benefits and may improve compliance. The study investigated whether once-weekly SC epoetin alfa was equivalent to twice- or thrice-weekly SC administration in maintaining anaemia correction in haemodialysis patients.. Eighty-three patients were randomly assigned to either once-weekly epoetin alfa (n = 44) or their original dose twice- or thrice-weekly regimen (control, n = 39) for 12 weeks. The haemoglobin concentration was maintained within the target range of 9.0-12.0 g/dL by adjusting the dose of epoetin alfa. All patients received intravenous iron supplementation, as required.. Stable haemoglobin levels were maintained without epoetin dose increases in the majority of patients in both groups (once-weekly group, 95.0%, control group, 91.4%). The mean haemoglobin levels at randomization at weeks 4, 8 and 12 were 10.7, 11.1, 11.3 and 11.0 g/dL, respectively, in the once-weekly group, and 10.5, 11.3, 11.5 and 11.3 g/dL, respectively, in the control group. The mean weekly dose of epoetin alfa at randomization at weeks 4, 8 and 12 was 142.8, 114.5, 108.6 and 104.5 IU/kg, respectively, in the once-weekly group, and 128.4, 116.0, 101.0 and 96.1 IU/kg/week, respectively, in the control group. No statistically significant between-group differences were apparent for changes in haemoglobin levels or epoetin alfa dosages at week 12.. This study demonstrates that once-weekly SC administration of epoetin alfa is as effective and safe as two or three times weekly administration in maintaining haemoglobin levels. Therefore, the once-weekly therapy using high dose of epoetin alfa is considered to be an efficient method in stable haemodialysis patients.

Topics: Aged; Anemia; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Hematocrit; Hemoglobins; Humans; Injections, Subcutaneous; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis

This multicentre, open-label prospective, randomized, comparative-group study evaluated the effects of maintaining haemoglobin (Hb) in pre-dialysis chronic kidney disease (CKD) patients.. A total of 197 patients were randomized to start subcutaneous epoetin-alpha (SC-EPO; EPREX; 1000 U twice weekly) at an early stage of anaemia to maintain Hb at 11.0 +/- 1.0 g/dl (group A, n = 65), or to allow Hb to fall to < or =9.0 g/dl before starting SC-EPO (group B, n = 132) (2000 U three times weekly); and subsequently maintaining Hb at 11.0 +/- 1.0 g/dl.. Of 132 patients randomized to group B, 55 progressed to treatment (-trigger). The study was prematurely terminated due to contraindication of the subcutaneous administration route. Mean weekly EPO doses at 1 year were 1471 U for group A; 820 U for group B; final doses were 2281 U for group A; 2099 U for group B. There was no significant difference between groups A and B with regard to left ventricular mass (-12.5 vs -9.7%; P = 0.82). In groups A and B, 48% and 52%, respectively, terminated the study because of dialysis/death, after a median of 36.3 and 27.3 months, respectively.. Early intervention to correct anaemia in CKD patients did not have a significant impact on LVM, the primary efficacy variable. Time to dialysis/death was not significantly different between groups A and B.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Female; Follow-Up Studies; Hematinics; Hemoglobins; Humans; Injections, Subcutaneous; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Renal Dialysis; Time Factors; Treatment Outcome

The required erythropoiesis-stimulating agent (ESA) dose varies when correcting anaemia in chronic kidney disease (CKD) patients. This analysis was performed to identify the prevalence of and factors associated with ESA hyporesponsiveness.. This analysis was a post hoc evaluation of epoetin alfa dosage requirements in a subgroup of patients from the Effect of early Correction of Anemia on the Progression of CKD study. The patients in this subgroup were randomly assigned to the high haemoglobin target group (14-15 g/dl for men and 13-14 g/dl for women) and completed a 4-month haemoglobin stabilization phase with complete epoetin dosage data. The relationship of demographics, disease characteristics and laboratory measures with epoetin dosage were evaluated using Pearson's correlation, association measures and analysis of covariance (ANCOVA) models.. Of the 93 patients evaluated in this subgroup analysis, 14 (15%) were hyporesponsive to epoetin (maximum dosage >100 IU/kg/week during stabilization). An ANCOVA analysis showed that 52% of the observed variability in epoetin dosage at completion of the stabilization phase could be accounted for by diabetes as the primary cause of kidney disease, angiotensin-converting enzyme (ACE) inhibitor/angiotensin receptor blocker (ARB) use, proteinuria, transferrin saturation, age, pre-treatment haemoglobin, geographical region, serum iron and body mass index (BMI). Unidentified patient characteristics accounted for an additional 16% of the dosage variance.. Older age, higher BMI, anaemia, ACE inhibitor/ARB use and diabetes as the primary cause of kidney disease are associated with increased epoetin requirements when normalizing haemoglobin in anaemic CKD patients.

Topics: Adolescent; Adult; Aged; Anemia; Australia; Canada; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Europe; Female; Follow-Up Studies; Glomerular Filtration Rate; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Treatment Outcome

A continuous erythropoietin receptor activator (C.E.R.A.) is currently in development for the treatment of anemia in patients with chronic renal disease (CRD) receiving or not receiving dialysis treatment.. The objectives of this study were to determine the optimal dose and administration schedule for IV C.E.R.A. in patients with CRD previously treated with IV epoetin alfa TIW, and to assess its tolerability profile in these patients. In addition, a 12-month extension phase was used to assess the long-term efficacy and tolerability of C.E.R.A.. This randomized, open-label, dose-finding study was conducted at 14 study centers across the United States. Male and female patients aged >/=18 years with CRD and CRD-related anemia and receiving treatment with IV epoetin alfa were enrolled. After a 2-week run-in period in which all patients continued to receive their previous epoetin treatment TIW, patients were switched to C.E.R.A. at 1 of 3 doses, determined by multiplying the previous weekly epoetin dose by 1 of 3 ratios (0.25 pg/150 IU, 0.4 pg/150 IU, or 0.6 pg/150 IU). Within each dose group, patients were randomized to 1 of 2 frequency subgroups: QW or Q2W Dose adjustments were not permitted during the first 6 weeks; the total dose during this period was the same for a particular dose group across the frequency subgroups. The primary efficacy parameter was change in hemoglobin (Hb) standardized to a 6-week period between baseline and the point when the patient had a dose change or blood transfusion, thus providing an estimate of Hb change based on starting dose. Following completion of a 19-week core period, patients could enter the 12-month extension period, aiming to maintain Hb concentrations between 11 and 12 g/dL. Adverse events (AEs) were recorded in the patients' case-report forms by the investigators throughout the study.. A total of 91 patients entered the core period (mean age, 58 years; 66% male); 10 patients withdrew prematurely during this period (4 owing to AEs and 6 for other reasons). Fifty-three patients continued into the extension period; 22 patients withdrew during this period (6 because of AEs, and 16 for other reasons). There was a significant dose-response effect (P < 0.001) and a significant effect of schedule (P < 0.002) for the primary efficacy end point. Stable Hb concentrations were maintained throughout the study (11-12 g/dL, with a narrow 95% CI). No significant difference between schedules was observed during the extension period, and few dose changes were required (mean, 4 and 2 per patient per year in the QW and Q2W groups, respectively). Nineteen and 22 patients experienced serious AEs during the core and extension periods, respectively, but only 1 event was considered related to study treatment. The most frequent AEs were headache and vomiting during the core study period and dizziness, fatigue, chest pain, and pyrexia during the extension period.. In this study, N C.E.R.A. provided effective maintenance of Hb concentrations in patients receiving dialysis treatment who were switched directly from N epoetin alfa TIW to N C.E.R.A. QW or Q2W C.E.R.A. was generally well tolerated.

Topics: Analysis of Variance; Anemia; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Injections, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Polyethylene Glycols; Recombinant Proteins; Regression Analysis; Renal Dialysis

To study efficacy and safety of long-term administration of epoetin and iron preparations in glomerulonephritis (GN) patients with chronic kidney disease (CKD) of stage III-IV in systemic diseases.. A total of 189 patients at predialysis stage of CKD (glomerular filtration rate between 15 and 60 ml/min) were randomized into 3 groups depending on GN etiology: primary GN (group 1, 123 patients), GN in systemic diseases (group 2, 45 patients), controls (group 3, 21 patients). Anemia was characterized not only by red cells indices but also by the level of serum ferritin, C-reactive protein (CRP), saturation of transferrin with iron. Remodeling of the heart was determined in all the patients at dopplerechocardiography estimating left ventricular myocardial mass, relative thickness of its wall.. Correction of anemia was achieved in all the patients with GN and CKD of stage III-IV in systemic diseases despite the activity of systemic disease (high blood level of CRP) and persistent nephritis activity (high proteinuria). In many patients from groups 1 and 2 who were initially diagnosed to have left ventricular hypertrophy (LVH) of excentric type LVH regressed after 6 months of anemia correction. In group 3 with untreated anemia frequency of LVH increased.. Treatment of anemia in GN patients with CKD of stage III-IV in systemic diseases needed higher doses of epoetin and parenteral iron preparations compared to patients with the above stages of CKD with primary GN.

Topics: Anemia, Iron-Deficiency; C-Reactive Protein; Disease Progression; Dose-Response Relationship, Drug; Echocardiography, Doppler; Epoetin Alfa; Erythropoietin; Female; Ferritins; Follow-Up Studies; Glomerular Filtration Rate; Hematinics; Hemoglobins; Humans; Hypertrophy, Left Ventricular; Iron; Iron Compounds; Kidney Failure, Chronic; Male; Recombinant Proteins; Severity of Illness Index; Treatment Outcome

To demonstrate the efficacy and safety of epoetin delta for the treatment of anaemia in dialysis patients with chronic kidney disease (CKD).. This was a 12-week, randomized, double-blind, active-comparator study. CKD patients who were naïve to epoetin treatment and had haemoglobin < 10 g/dL were randomized to epoetin delta 15, 50, 150, or 300 IU/kg or epoetin alfa 50 IU/kg. Patients initially entered a correction phase until they recorded haemoglobin of > or = 11.5 g/dL for two consecutive weekly measurements or one haemoglobin measurement of > or = 13 g/dL (correction success). A maintenance phase followed where the dose was adjusted to maintain haemoglobin > or = 10.5 g/dL. Maintenance success was defined as haemoglobin > 10.5 g/dL at Week 12. Total success was defined as achieving maintenance and correction success.. The primary objective was to demonstrate that the proportion of patients achieving total success was greater in the pooled 150 IU/kg and 300 IU/kg groups compared with the 15 IU/kg dose group.. Total success was achieved in 55.6% of patients in the pooled highest epoetin delta group compared with 4.5% in the lowest dose group. There was no significant difference in total success for the epoetin delta and epoetin alfa 50 IU/kg groups. Significant increases in haemoglobin and haematocrit levels were observed in the 150 and 300 IU/kg dose groups. Adverse events occurred at frequencies expected for this patient group.. Epoetin delta was effective in increasing haemoglobin levels in patients with baseline haemoglobin of < 10 g/dL.

Topics: Adult; Aged; Anemia; Dose-Response Relationship, Drug; Double-Blind Method; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hematocrit; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Treatment Outcome

It is unclear whether physiologic hemoglobin targets lead to cardiac benefit in incident hemodialysis patients without symptomatic heart disease and left ventricular dilation. In this randomized, double-blind study, lower (9.5 to 11.5 g/dl) and higher (13.5 to 14.5 g/dl) hemoglobin targets were generated with epoetin alpha over 24 wk and maintained for an additional 72 wk. Major eligibility criteria included recent hemodialysis initiation and absence of symptomatic cardiac disease and left ventricular dilation. The primary outcome measure was left ventricular volume index (LVVI). The study enrolled 596 patients. Mean age, duration of dialysis therapy, baseline predialysis hemoglobin, and LVVI were 50.8 yr, 0.8 yr, 11.0 g/dl, and 69 ml/m2, respectively; 18% had diabetic nephropathy. Mean hemoglobin levels in the higher and lower target groups were 13.3 and 10.9 g/dl, respectively, at 24 wk. Percentage changes in LVVI between baseline and last value were similar (7.6% in the higher and 8.3% in the lower target group) as were the changes in left ventricular mass index (16.8 versus 14.2%). For the secondary outcomes, the only between-group difference was an improved SF-36 Vitality score in the higher versus the lower target group (1.21 versus -2.31; P = 0.036). Overall adverse event rates were similar in both target groups; higher (P < 0.05) rates of skeletal pain, surgery, and dizziness were seen in the lower target group, and headache and cerebrovascular events were seen in the higher target group. Normalization of hemoglobin in incident hemodialysis patients does not have a beneficial effect on cardiac structure, compared with partial correction.

Topics: Adult; Aged; Anemia; Double-Blind Method; Epoetin Alfa; Erythropoietin; Female; Heart Diseases; Hematinics; Humans; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis

Recombinant human erythropoietin (EPO) is used for the treatment of last stage renal anemia. A new EPO preparation was obtained in Cuba in order to make this treatment fully nationally available. The aim of this study was to compare the pharmacokinetic, pharmacodynamic and safety properties of two recombinant EPO formulations in patients with anemia due to end-stage renal disease on hemodialysis.. A parallel, randomized, double blind study was performed. A single 100 IU/Kg EPO dose was administered subcutaneously. Heberitro (Heber Biotec, Havana, formulation A), a newly developed product and Eprex (CILAG AG, Switzerland, formulation B), as reference treatment were compared. Thirty-four patients with anemia due to end-stage renal disease on hemodialysis were included. Patients had not received EPO previously. Serum EPO level was measured by enzyme immunoassay (EIA) during 120 hours after administration. Clinical and laboratory variables were determined as pharmacodynamic and safety criteria until 216 hours.. Both groups of patients were similar regarding all demographic and baseline characteristics. EPO kinetics profiles were similar for both formulations; the pharmacokinetic parameters were very close (i.e., AUC: 4667 vs. 4918 mIU.h/mL; Cmax: 119.1 vs. 119.7 mIU/mL; Tmax: 13.9 vs. 18.1 h; half-life, 20.0 vs. 22.5 h for formulations A and B, respectively). The 90% confidence intervals for the ratio between both products regarding these metrics were close to the 0.8-1.25 range, considered necessary for bioequivalence. Differences did not reach 20% in any case and were not determined by a formulation effect, but probably by a patients' variability effect. Concerning pharmacodynamic features, a high similitude in reticulocyte counts increments until 216 hours and the percentage decrease in serum iron until 120 hours was observed. There were no differences between formulations regarding the adverse events and their intensity. The more frequent events were pain at injection site (35.3%) and hypertension (29%). Additionally, further treatment of the patients with the study product yielded satisfactory increases in hemoglobin and hematocrit values.. The formulations are comparable. The newly developed product should be acceptable for long-term application.

Topics: Adult; Aged; Anemia; Double-Blind Method; Epoetin Alfa; Erythropoietin; Female; Follow-Up Studies; Hematinics; Hematocrit; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Treatment Outcome

The purpose of this study was to compare erythropoietin dosage requirements during subcutaneous versus intravenous administration in a hemodialysis population. Hemodialysis patients receiving subcutaneous epoetin alfa were switched to the intravenous route using a prospective, crossover design. Baseline anemia parameters were measured at months -2, -1, and 0 when patients were receiving subcutaneous dosing and compared to months 4, 5, and 6 after the switch to intravenous dosing. Ninety-eight patients were enrolled into the study with an average age of 54.8 years. Over the course of the study, 34 patients were excluded from analysis, leaving 64 patients with complete hemoglobin and erythropoietin dosing data throughout the subcutaneous and intravenous evaluation periods. In these patients, the dose of erythropoietin increased significantly from the subcutaneous to the intravenous period (7567.7 to 10229.2 IU/wk). The conversion of hemodialysis patients from the subcutaneous to the intravenous route of administration significantly increased epoetin alfa dosage requirements.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Cross-Over Studies; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Ferritins; Hematinics; Hemoglobins; Humans; Infusions, Intravenous; Injections, Subcutaneous; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Renal Dialysis

To determine whether extended epoetin alfa dosing schedules of up to once every four weeks are as effective as weekly dosing in maintaining hemoglobin (Hb) levels in patients with anemia of chronic kidney disease (CKD).. This randomized, open-label trial enrolled patients with anemia of CKD not on dialysis. Patients were required to have a stable Hb level (> or = 11.0 g/dl) and to have been previously receiving epoetin alfa for two or more months. Patients were randomized to one of four subcutaneously administered epoetin alfa dosing regimens: 10,000 units (U) once weekly (QW), 20,000 U every two weeks (Q2W), 30,000 U every three weeks (Q3W) or 40,000 U every four weeks (Q4W). Dose reductions, but not escalations, were permitted. Patients received treatment for a total of 16 weeks. The primary endpoint for the trial was the mean final Hb measurements of the QW, Q2W, Q3W, and Q4W groups. The primary efficacy analyses were non-inferiority assessments of the mean final Hb measurements of the Q2W, Q3W, and Q4W groups, compared with the QW group. The primary efficacy analyses were performed using a modified intent-to-treat (MITT) population, defined as all patients meeting all inclusion/exclusion criteria (or, if not satisfying all criteria, were granted an exemption at study entry), and who were randomized and received at least one dose of study medication. A per-protocol population, based on all patients who met the MITT criteria and completed the entire study, was used to evaluate the robustness of the MITT results. Quality of life was assessed for all dosing groups throughout the study. Safety was based on all patients randomized who received at least one dose of study medication.. A total of 519 patients were enrolled; 445 were included in the MITT population. The four treatment groups were comparable with respect to baseline characteristics. The primary etiologies of CKD were diabetes (45.7%) and hypertension (29.9%). The mean baseline Hb, serum creatinine and glomerular filtration rate for all patients were 11.9 +/- 0.8 g/dl, 3.1 mg/dl, and 21.1 ml/min/1.73 m2, respectively. The mean baseline transferrin saturation was 25.2% and the mean ferritin was 201.9 ng/ml for all patients. All groups had a mean final Hb of > 11.0 g/dl. The mean final Hb levels of the Q2W and Q4W groups were statistically non-inferior to the QW group. The results of the per-protocol analysis were consistent with the MITT results. In addition, 93.5%, 89.5%, 77.2%, and 76.0% of patients maintained a mean Hb > or = 11.0 g/dl throughout the course of the study in the QW, Q2W, Q3W, and Q4W groups, respectively. Quality of life was maintained or improved from baseline to final within each dosing group. There were no significant differences in the mean final quality of life scores between the QW group and the Q2W, Q3W, and Q4W groups. Among the 513 patients evaluated for safety, epoetin alfa was well tolerated with no differences in adverse events between groups. The incidence of thrombotic adverse events was low (2.5% of patients), as was mortality (1.4% of patients).. Approximately 90% of patients dosed once every two weeks and over 75% of patients dosed once every three or four weeks maintained mean Hb levels > or = 11.0 g/dl, consistent with the Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines. This study suggests that extended epoetin alfa dosing schedules are effective and safe for maintaining Hb, and may offer the possibility of increased flexibility and convenience for the majority of patients with the anemia of CKD.

Topics: Aged; Analysis of Variance; Anemia; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Quality of Life; Recombinant Proteins; Treatment Outcome

Of the known risk factors for chronic kidney disease (CKD), race represents one that is non-modifiable, while smoking is another that is modifiable. Moreover, smoking tends to increase red blood cell mass, which is frequently diminished in CKD. No studies have examined the interplay of race with smoking on anaemia management in patients with CKD.. We examined the effects of smoking on anaemia management in CKD and its variation across race in a previously conducted study of CKD patients (n = 1312) initiated on weekly epoetin alfa and followed for 16 weeks. Smoking status was classified as current vs non-smoker. Race was classified as African-American vs non-African-American. Changes in estimated glomerular filtration rate, urinary albumin excretion, and erythropoietic response to weekly epoetin alfa were examined.. Overall, African-Americans had lower baseline Hb than non-African-Americans. African-American non-smokers did not mount an erythropoetic response comparable to other non-smokers by final Hb (mean 11.29 g/dl vs 11.64 g/dl, P<0.001) or week 16 Hb (mean 11.61 g/dl vs 11.86 g/dl, P = 0.02). However, African-American smokers had a more significant erythropoietic response than their non-smoking counterparts and were comparable to their smoking non-African-American counterparts. There was no effect of smoking on renal function or urinary protein excretion over the course of the study.. African-American non-smokers exhibit a diminished response to standard epoetin alfa dosing than non-smokers in other races. However, African-American smokers with CKD exhibit a response to epoetin alfa comparable to patients of other races. These findings may have implications for African-Americans who have CKD-related anaemia.

Topics: Aged; Anemia; Black or African American; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoiesis; Erythropoietin; Female; Ferritins; Follow-Up Studies; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Risk Factors; Smoking; Treatment Outcome; United States

It is not known whether prevention of anemia among patients with chronic kidney disease would affect the development or progression of left ventricular (LV) hypertrophy. A randomized controlled trial was performed with 155 patients with chronic kidney disease (creatinine clearance, 15 to 50 ml/min), with entry hemoglobin concentrations ([Hb]) of 110 to 120 g/L (female patients) or 110 to 130 g/L (male patients). Patients were monitored for 2 yr or until they required dialysis; the patients were randomized to receive epoetin alpha as necessary to maintain [Hb] between 120 and 130 g/L (group A) or between 90 and 100 g/L (group B). [Hb] increased for group A (from 112 +/- 9 to 121 +/- 14 g/L, mean +/- SD) and decreased for group B (from 112 +/- 8 to 108 +/- 13 g/L) (P < 0.001, group A versus group B). On an intent-to-treat analysis, the changes in LV mass index for the groups during the 2-yr period were not significantly different (2.5 +/- 20 g/m(2) for group A versus 4.5 +/- 20 g/m(2) for group B, P = NS). There was no significant difference between the groups in 2-yr mean unadjusted systolic BP (141 +/- 14 versus 138 +/- 13 mmHg) or diastolic BP (80 +/- 6 versus 79 +/- 7 mmHg). The decline in renal function in 2 yr, as assessed with nuclear estimations of GFR, also did not differ significantly between the groups (8 +/- 9 versus 6 +/- 8 ml/min per 1.73 m(2)). In conclusion, maintenance of [Hb] above 120 g/L, compared with 90 to 100 g/L, had similar effects on the LV mass index and did not clearly affect the development or progression of LV hypertrophy. The maintenance of [Hb] above 100 g/L for many patients in group B might have been attributable to the relative preservation of renal function.

Topics: Anemia; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Time Factors

Anaemia correction in patients with end-stage renal disease has been enhanced following the use of epoetin alfa or beta and there are a number of studies detailing its application. Dialysis centres are dealing with greater numbers of elderly patients and anaemia correction in these individuals may differ by virtue of co-existing comorbidity and their age.. The aim of this study was to examine the response of the elderly patients to anaemia correction using a locally devised anaemia correction protocol while receiving dialysis.. An incident, non-randomised, cohort observational study in a single centre was used to compare the correction of anaemia in a population of elderly (> or =65 years of age) and young dialysis patients. All incident patients starting peritoneal dialysis and haemodialysis (HD) between January 1998 and December 2000 were selected and treated using a locally devised anaemia correction protocol and observed for at least 1 year. Anaemia correction following adjustments for factors such as age, comorbidity, dialysis type, dialysis access type and predialysis nephrological care was assessed.. 198 patients commenced dialysis with 86 elderly patients (mean age +/- SD 73.7 +/- 4.9 years). The elderly patients had similar periods of predialysis nephrological care as the younger patients. Most patients received HD and required a tunnelled dialysis catheter (TC) as vascular access. Equivalent numbers of elderly patients received peritoneal dialysis. Comorbid scores were greater in the elderly and patient survival was dependent upon these comorbid factors. Following the strict use of TCs, patient survival was similar to those patients commencing HD with arterio-venous fistulae. Anaemia correction in the elderly was similar to the younger patients, with a median haemoglobin of 11.3 g/dL. By 6 months of dialysis, most patients achieved the UK Renal Association anaemia correction standard (haemoglobin above 10 g/dL). The elderly patients maintained significantly higher serum ferritin levels throughout (median 209 microg/L) and required less epoetin alfa or beta (median 91.6 units/kg/wk), indicating that functional iron deficiency in the elderly dialysis patients is less. Intravenous iron sucrose doses were similar in both age groups and iron overload (serum ferritin above 800 microg/L) had been avoided following the use of the intravenous iron protocol.. The study has noted that elderly patients responded to anaemia corrective therapies as well as the younger patients, despite greater levels of comorbidity while requiring less epoetin alfa or beta.

Topics: Aged; Aged, 80 and over; Aging; Anemia; Comorbidity; Epoetin Alfa; Erythropoietin; Ferritins; Geriatrics; Humans; Kidney Failure, Chronic; Middle Aged; Peritoneal Dialysis; Recombinant Proteins; Renal Dialysis; Survival Analysis; Treatment Outcome

Darbepoetin alfa is an erythropoiesis-stimulating glycoprotein with up to 3 times longer half-life than recombinant human erythropoietin (rHuEPO) in humans. The aim of this study was to assess the efficacy and safety of darbepoetin alfa given once every other week as treatment of anemia in predialysis patients with chronic renal failure (CRF) previously treated with once-weekly epoetin alfa. A total of 42 CRF patients were included, all of whom had previously been treated with epoetin alfa and showed stable hemoglobin (Hb) levels without dose changes during the last 8 weeks prior to enrolment in this study. All patients received s.c. darbepoetin alfa once every other week at doses calculated from the protein mass equivalence between rHuEPO and darbepoetin alfa. Follow-up lasted for 24 weeks. Dose adjustments were conducted to preserve target Hb levels between 11 and 13 g/dl. Thirty-nine patients completed the 24 weeks of study. Hb levels increased during follow-up [mean values of 0.39 (p < 0.002), 0.58) (p < 0.001), and 0.83 g/dl (p < 0.001) at 8, 16 and 24 weeks, respectively] despite reducing the darbepoetin alfa dose up to 15% at 24 weeks [from 0.192 microg/kg body weight to 0.185, 0.178 and 0.163 at 8, 16, and 24 weeks, respectively (p < 0.001)]. No adverse events related to darbepoetin alfa were reported. In conclusion, these results show s.c. administration of darbepoetin alfa once every other week was superior to weekly epoetin alfa as a maintenance treatment for anemia in predialysis CRF patients, since the former provided higher Hb levels. Moreover, darbepoetin alfa administration was safe in these patients.

Topics: Aged; Anemia; Darbepoetin alfa; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Follow-Up Studies; Hematinics; Humans; Kidney Failure, Chronic; Male; Prospective Studies; Recombinant Proteins

Anaemia is a key component of diabetic nephropathy, but its importance has only recently been recognised. Recombinant human erythropoietin (epoetin) is an established treatment for renal anaemia, and may help to reduce complications associated with diabetic nephropathy, such as cardiovascular disease. The limited experience with the use of epoetin in this patient group prompts the urgent need for clinical data on anaemia correction in early diabetic nephropathy, particularly with regard to benefits on cardiovascular risk reduction. The Anaemia CORrection in Diabetes (ACORD) study will investigate the effects of anaemia correction on cardiac structure and function in patients with early diabetic nephropathy. This 15-month multicentre study will recruit 160 adult patients with diabetes, mild or moderate chronic kidney disease (with creatinine clearance >or=30 ml/min at screening) and moderate anaemia (haemoglobin [Hb], 10.5-13.0 g/dl). Patients will be randomised to one of two groups: the early treatment group will receive subcutaneous epoetin beta (NeoRecormon) at study entry to maintain target Hb levels of 13-15 g/dl, while the control group will reflect current practice and will not receive epoetin therapy until Hb levels decline below 10.5 g/dl. The primary efficacy variable, change in left ventricular mass index, will be evaluated at 15 months following randomisation; secondary efficacy variables will include changes in cardiac structure and function over the study period. The ACORD study should provide valuable information on the benefits of anaemia correction in patients with early diabetic nephropathy. The study will also increase awareness of the importance of treating anaemia associated with diabetes.

Topics: Anemia; Clinical Trials as Topic; Diabetic Nephropathies; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Randomized Controlled Trials as Topic; Recombinant Proteins; Survival Analysis; Time Factors

Catheter-related infection (CRI) is a major cause of morbidity and mortality in patients receiving hemodialysis. Antibiotic locking of these catheters has been shown to increase both the success of systemic antibiotic treatment in line sepsis, and to reduce the incidence of sepsis. We have studied the use of gentamicin locking of catheters (in combination with standard heparin rather than previously reported citrate) to reduce CRI rates. Furthermore, we have investigated the effects of this strategy on epoetin requirements and vascular access function.. Fifty patients were studied. Patients were randomized to catheter-restricted filling with either standard heparin (5000 IU/mL) alone, or gentamicin and heparin (5 mg/mL). Epoetin requirements and hemoglobin response were monitored over the study period.. The gentamicin-locked group suffered only one infective episode (0.3/1000 catheter days) compared to 10 episodes in six patients in the heparin alone group (4/1000 catheter days, P= 0.02). The isolated organisms were equally split between Staphylococcal species and coliforms. There were no statistically significant differences in delivered dialysis dose (Kt/V) or QA between the two groups. Use of antibiotic locking was associated with both a higher mean hemoglobin (10.1 +/-0.14 g/dL vs. 9.2 +/- 0.17 g/dL in the heparin group, P= 0.003) and a lower mean epoetin dose (9000 +/- 734 IU/week vs. 10790 +/-615 IU/week in the heparin group, P= 0.04).. The practice of locking newly inserted tunneled central venous catheters with gentamicin and heparin is an effective strategy to reduce line sepsis rates, and is associated with beneficial effects on epoetin requirements.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Anti-Bacterial Agents; Anticoagulants; Catheterization; Cross Infection; Epoetin Alfa; Erythropoietin; Female; Gentamicins; Hematinics; Heparin; Humans; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Sepsis

Membrane biocompatibility has long been thought to be relevant to hemodialysis outcomes and, possibly, renal anemia.. We performed a randomized, controlled, single-center study comparing the consequences on renal anemia of 2 dialyzers of equivalent performance, but different composition, during 7 months. Two hundred eleven patients of an unselected dialysis population of 235 patients gave informed consent to undergo random assignment to either group A (SF170E; modified cellulose triacetate/midflux membrane; Nipro, Osaka, Japan) or group B (HF80LS; polysulfone/high-flux membrane; Fresenius, Bad Homburg, Germany). Anemia management was identical in both treatment groups and followed strict clinical protocols managed by computer algorithms. Dialysis adequacy, hemoglobin (Hb) level, ferritin level, percentage of red blood cell hypochromicity, C-reactive protein (CRP) level, and intravenous iron and epoetin doses were monitored monthly.. One hundred seventy-seven patients completed the 7-month study. Equilibrated Kt/V increased in both groups. Hb outcome improved overall, but did not differ between the 2 study groups. Epoetin dose was not significantly different after 7 months compared with baseline in either group. Hb level, epoetin dose, iron status, CRP level, dialysis Kt/V, and residual renal function did not differ between the 2 groups. A slight but significant negative correlation was identified between dialysis Kt/V and Hb level in the population as a whole (Spearman's correlation, -0.16; P = 0.04).. No significant epoetin-sparing effect was identified through the use of the high-flux polysulfone HF80LS membrane over the modified cellulose triacetate SF170E membrane. Although not a primary outcome for this study, there was a suggestion of benefit of improved Hb level, without increased need for epoetin, through increasing delivered dialysis dose.

Topics: Adult; Aged; Anemia; C-Reactive Protein; Cellulose; Epoetin Alfa; Erythrocytes; Erythropoietin; Female; Ferritins; Hemoglobins; Humans; Iron; Kidney Failure, Chronic; Male; Membranes, Artificial; Middle Aged; Parathyroid Hormone; Phosphorus; Polymers; Potassium; Recombinant Proteins; Renal Dialysis; Sulfones

Topics: Adult; Aged; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Injections, Intravenous; Injections, Subcutaneous; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis

The objective of the study was to evaluate and compare the safety and effectiveness of epoetin omega (produced in baby hamster kidney cells) and epoetin alfa (produced in Chinese hamster ovary cells) in sustaining the correction of anemia in maintenance hemodialysis patients. The study, a prospective and controlled crossover, was completed in 38 stable patients treated with both epoetins for 24 weeks. Group A (17 patients) started with epoetin omega, and Group B (21 patients) started with epoetin alfa. After 24 weeks, a 4 week crossover (wash out) was made: Group A was switched to epoetin alfa and group B to epoetin omega for the next test period of 24 weeks. Both epoetins were administered subcutaneously after each dialysis. Doses were adjusted with the aim of maintaining a target hemoglobin level between 10 and 12 g/dl (hematocrit 30% to 35%). The mean weekly dose of epoetin omega/kg body weight (BW) was 67 +/- 43 U. The mean weekly dose of epoetin alfa/kg BW was 86 +/- 53 U. The average of all mean values of hemoglobin (Hb) during treatment with epoetin omega was 11.4 +/- 0.7 g/dl (hematocrit 34 +/- 2%), and during treatment with epoetin alfa was 11.3 +/- 0.7 g/dl (hematocrit 33 +/- 2%) (not significant). Thromboses of vascular access occurred in 3 patients during an epoetin omega treatment and in 3 patients during epoetin alfa treatment. At the site of injection, only 1 patient described a mild pain when treated with epoetin omega and only 6 patients when treated with epoetin alfa. In conclusion, both epoetin omega and epoetin alfa were effective in correcting the anemia of all studied patients. However, lower doses of epoetin omega were needed to maintain the same target hemoglobin level. No serious side effects with either epoetin were noted. The authors believe that additional comparisons of different epoetin preparations should be performed and will provide better insight into their biological activity and clinical responsiveness.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Cross-Over Studies; Epoetin Alfa; Erythropoietin; Female; Hematocrit; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Renal Dialysis; Treatment Outcome

Iron sucrose has been used to provide intravenous (IV) iron therapy to patients outside the United States for more than 50 years. In a multicenter North American clinical trial, we determined the efficacy and safety of iron sucrose therapy in patients with dialysis-associated anemia, evidence of iron deficiency, and below-target hemoglobin (Hgb) levels despite epoetin therapy. Evidence of iron deficiency included a transferrin saturation (Tsat) less than 20% and ferritin level less than 300 ng/mL, and below-target Hgb levels included values less than 11.0 g/dL. We administered iron sucrose in 10 doses, each administered undiluted as 100 mg IV push over 5 minutes, without a prior test dose. We assessed efficacy by determining the subsequent change in Hgb, Tsat, and ferritin values. We assessed safety by recording blood pressure and adverse events after iron sucrose injection and comparing results with those for the same patients during an observation control period. Results showed a significant increase in Hgb level that was first evident after three doses of iron sucrose and persisted at least 5 weeks after the 10th dose. Tsat and ferritin levels also increased significantly and remained elevated. In 77 enrolled patients, including those with previous iron dextran sensitivity, other drug allergies, or concurrent angiotensin-converting enzyme inhibitor use, we saw no serious adverse drug reactions and no change in intradialytic blood pressure associated with iron sucrose administration. We conclude that iron sucrose injection administered as 1,000 mg in 10 divided doses by IV push without a prior test dose is safe and effective for the treatment of iron deficiency in patients with dialysis-associated anemia.

Topics: Aged; Anemia, Iron-Deficiency; Epoetin Alfa; Erythrocyte Indices; Erythropoietin; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Hemoglobins; Humans; Injections, Intravenous; Iron; Kidney Failure, Chronic; Middle Aged; Prospective Studies; Recombinant Proteins; Renal Dialysis

Transient ST-segment depression measured on ambulatory ECG monitors has been described as representing silent ischemia. Patients who demonstrate silent ischemia have been reported to show increased mortality compared to patients without silent ischemia. We undertook this study to determine if the correction of anemia in End Stage Renal Disease (ESRD) patients from (+/- = standard deviation) 30 +/- 3 to 42 +/- 3 with the use of Epoietin alfa would result in decreased silent ischemia in patients with clinically evident ischemic heart disease or congestive heart failure.. Thirty one ESRD patients with congestive heart failure or patients with clinically-evident ischemic heart disease were randomized into one of two arms. Patients in Group A had their hematocrit increased with the use of slowly escalating doses of Epoietin alfa to 42 +/- 3% and patients in Group B were maintained with a hematocrit of 30 +/- 3% throughout the course of the study. All patients had a 24 hour Holter monitor recording at baseline and at 28 weeks after randomization (when they had reached their target hematocrit). Significant silent ischemia was considered to be present if patients demonstrated at least 60 seconds of > or = 1 mm ST segment depression.. Fifteen patients were randomized to Group A and 16 patients were randomized to Group B. The mean hematocrit increased in group A from 29.1 +/- 2.4% to 40.8 +/- 5.2% after 30 weeks. The mean hematocrit in Group B remained stable at 30 +/- 3% throughout the course of the study. Ten patients demonstrated silent ischemia at baseline. At follow up patients in group A demonstrated a mean of 1.7 +/- 4.9 minutes of ischemia compared to 1.1 +/- 3.4 minutes in group B. These were not significantly different. A similar number of patients in group A and Group B required adjustments in their anti-anginal medication during the course of the study.. It is possible to increase hematocrit to near normal levels in hemodialysis with the administration of exogenous Epoietin alfa. The increase in hematocrit form 30 +/- 3% to 42 +/- 3% is not associated with a change in the level of silent ischemia these patients demonstrate.

Topics: Anemia; Electrocardiography; Electrocardiography, Ambulatory; Epoetin Alfa; Erythropoietin; Female; Heart Failure; Hematinics; Hematocrit; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Myocardial Ischemia; Prognosis; Recombinant Proteins; Renal Dialysis

Angiotensin-converting enzyme (ACE) inhibitors may exacerbate anemia in patients with chronic renal failure, as well as in dialysis patients. To better answer this question, a prospective, crossover study was conducted to evaluate the effect of ACE inhibitors on recombinant human erythropoietin (rHuEPO) requirements in hemodialysis patients. Patients administered an ACE inhibitor when entering the study remained on this drug for the initial 4 months and were then switched to another antihypertensive agent for 4 more months. Patients not initially administered an ACE inhibitor were switched to lisinopril at 4 months. rHuEPO doses were adjusted using a sliding scale based on weekly laboratory hematocrit values. The inclusion criteria were met by 51 patients undergoing dialysis. Demographics were as follows: 61% were women, 64% were black, 46% had diabetes, average age was 53.2 +/- 13.3 years, and time on hemodialysis was 38.0 +/- 44.5 months. Thirty-three patients completed the study. Hematocrit averaged 32.7% +/- 1.9% while on ACE inhibitor therapy and 33.1% +/- 2.1% off ACE inhibitor therapy (P = 0.217). There was no difference in rHuEPO dose per treatment during each period (3,500 +/- 1,549 U on ACE inhibitor therapy versus 3,312 +/- 1,492 U off ACE inhibitor therapy; P = 0.300). No significant differences were found in degree of blood pressure control or various clinical and laboratory parameters that might be associated with rHuEPO resistance between the two periods. Similarly, no differences were found in hospitalization days, duration of infections, or transfusion requirements. These findings suggest that ACE inhibitors do not contribute to rHuEPO resistance in hemodialysis patients.

Topics: Anemia; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Blood Transfusion; Cross-Over Studies; Diabetes Complications; Drug Resistance; Epoetin Alfa; Erythropoietin; Female; Follow-Up Studies; Hematinics; Hematocrit; Hospitalization; Humans; Infections; Kidney Failure, Chronic; Lisinopril; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Renal Dialysis; Time Factors

Since the earliest reports of the use of Epoetin alfa in hemodialysis patients, it has been described that Epoetin alfa may exacerbate preexisting hypertension or induce hypertension in End Stage Renal Disease (ESRD) patients not previously hypertensive. We undertook this study to determine if the correction of anemia in ESRD patients with cardiac disease from a hematocrit of 30+/-3% to 42+/-3% with the use of Epoetin alfa would result in increased blood pressure. This study was a substudy of the "Normal hematocrit Study".. Thirty-one patients were randomized into one of two arms. Patients in Group A had their hematocrit increased with the use of slowly escalating doses of Epoetin alfa to 42+/-3% and patients in Group B were maintained with a hematocrit of 30+/-3% throughout the course of the study. All patients had their blood pressure recorded with a 24 hour ambulatory BP device at study entry and at 28 weeks following randomization when they had achieved their target hematocrit. Pre-dialysis systolic and diastolic BP was also recorded.. The mean hematocrit increased in Group A from 29.1+/-2.4% to 40.8+/-5.2% after 30 weeks. The hematocrit in Group B remained stable at 30+/-3% throughout the course of the study. There was no difference in mean daytime, mean nighttime or 24 hour systolic or diastolic blood pressure between Groups A and B at either baseline or follow-up. Neither was there a difference in mean pre-dialysis systolic or diastolic BP between Groups A or B at baseline or Follow-up. Four patients in Group A and 4 patients in Group B required an increase in their antihypertensive medication during the course of the study.. It is possible to increase hematocrit to normal levels in hemodialysis with the administration of Epoetin alfa. The increase in hematocrit from 30+/-3% to 42+/-3% is not associated with increased blood pressure.

Topics: Adult; Aged; Anemia; Blood Pressure Monitoring, Ambulatory; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Female; Follow-Up Studies; Hematinics; Hematocrit; Humans; Kidney Failure, Chronic; Male; Middle Aged; Myocardial Ischemia; Recombinant Proteins; Reference Values; Renal Dialysis; Treatment Outcome

To determine the effects of different haemoglobin (Hb) levels on exercise performance and associated electrolyte changes, a prospective, randomized, double-blinded crossover study was completed in 14 haemodialysis patients.. Performance and changes in arterial [K+] and lactate were compared at rest and during a maximal incremental cycling exercise at a Hb concentration ([Hb]) of 10 g/dl ([Hb]10) and 14 g/dl ([Hb]14) following an initial baseline test (Hb: 8.3 +/- 0.2 g/dl, mean +/- SEM). Ages ranged from 23 to 65 years and patients were divided into younger (age 23-45 years, n = 9) and older (aged 55-65 years, n = 5) groups.. Peak work rate and VO2 peak were higher at [Hb]14 than at [Hb]10. 145 +/- 9 vs 134 +/- 9 W, mu +/- SEM, P < 0.01, and 1.90 +/- 0.11 vs 1.61 +/- 0.11 l/min, P < 0.01, respectively. Improvements were demonstrated in both younger and older groups at the higher target [Hb], with an improved aerobic performance evident particularly in younger patients. However, performance remained below that predicted for comparable sedentary controls. Resting plasma [K+] was raised at both [Hb]10 and [Hb]14 compared with baseline (P < 0.01) although the change in [K+] from rest to peak exercise (delta[K+]) was similar at each level. The delta[K+] per unit work performed (used as a marker of K+ regulation) was, however, inversely related to the [Hb] (baseline: 80 +/- 12 micromol/l/kJ vs [Hb]10, 61 +/- 8, P < 0.01, vs [Hb]14. 49 +/- 7, P < 0.05). Exercise induced a significant but similar rise in lactate concentration at both target [Hb] (P < 0.001), which remained markedly elevated for at least 10 min after exercise in both younger and older groups.. These data demonstrate that a physiological [Hb] improves, but does not normalize, exercise performance in end-stage renal failure. Both younger and older patients appear to benefit similarly from the enhanced oxygen transport. Impaired K+ regulation is apparently related to [Hb] and could well contribute to the observed limitations in performance.

Topics: Adult; Aged; Anemia; Blood Volume; Cross-Over Studies; Double-Blind Method; Epoetin Alfa; Erythropoietin; Exercise; Exercise Test; Hemoglobins; Humans; Kidney Failure, Chronic; Middle Aged; Plasma Volume; Potassium; Prospective Studies; Recombinant Proteins; Renal Dialysis

Several studies have suggested that if recombinant human erythropoietin (epoetin) is administered subcutaneously rather than intravenously, a lower dose may be sufficient to maintain the hematocrit at a given level.. In a randomized, unblinded trial conducted at 24 hemodialysis units at Veterans Affairs medical centers, we assigned 208 patients who were receiving long-term hemodialysis and epoetin therapy to treatment with either subcutaneous or intravenous epoetin. The dose was initially reduced until the hematocrit was below 30 percent and then was gradually increased to a level that would maintain the hematocrit in the range of 30 to 33 percent for 26 weeks. We compared the average doses in the 26-week maintenance phase and the discomfort associated with the two routes of administration.. For the 107 patients treated by the subcutaneous route, the average weekly dose of epoetin during the maintenance phase was 32 percent less than that for the 101 patients treated by the intravenous route (mean [+/-SD], 95.1+/-75.0 vs. 140.3+/-88.5 U per kilogram of body weight per week; P<0.001). Only one patient in the subcutaneous-therapy group withdrew from the study because of pain at the injection site, and 86 percent rated the pain associated with subcutaneous administration as ranging from absent to mild.. In patients receiving hemodialysis, subcutaneous administration of epoetin can maintain the hematocrit in a desired target range, with an average weekly dose of epoetin that is lower than with intravenous administration.

Topics: Algorithms; Anemia; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hematocrit; Humans; Infusions, Intravenous; Injections, Subcutaneous; Iron; Kidney Failure, Chronic; Male; Middle Aged; Pain; Recombinant Proteins; Renal Dialysis

In patients with end-stage renal disease, anemia develops as a result of erythropoietin deficiency, and recombinant human erythropoietin (epoetin) is prescribed to correct the anemia partially. We examined the risks and benefits of normalizing the hematocrit in patients with cardiac disease who were undergoing hemodialysis.. We studied 1233 patients with clinical evidence of congestive heart failure or ischemic heart disease who were undergoing hemodialysis: 618 patients were assigned to receive increasing doses of epoetin to achieve and maintain a hematocrit of 42 percent, and 615 were assigned to receive doses of epoetin sufficient to maintain a hematocrit of 30 percent throughout the study. The median duration of treatment was 14 months. The primary end point was the length of time to death or a first nonfatal myocardial infarction.. After 29 months, there were 183 deaths and 19 first nonfatal myocardial infarctions among the patients in the normal-hematocrit group and 150 deaths and 14 nonfatal myocardial infarctions among those in the low-hematocrit group (risk ratio for the normal-hematocrit group as compared with the low-hematocrit group, 1.3; 95 percent confidence interval, 0.9 to 1.9). Although the difference in event-free survival between the two groups did not reach the prespecified statistical stopping boundary, the study was halted. The causes of death in the two groups were similar. The mortality rates decreased with increasing hematocrit values in both groups. The patients in the normal-hematocrit group had a decline in the adequacy of dialysis and received intravenous iron dextran more often than those in the low-hematocrit group.. In patients with clinically evident congestive heart failure or ischemic heart disease who are receiving hemodialysis, administration of epoetin to raise their hematocrit to 42 percent is not recommended.

Topics: Aged; Anemia; Epoetin Alfa; Erythropoietin; Female; Heart Failure; Hematocrit; Humans; Iron; Kidney Failure, Chronic; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Prospective Studies; Recombinant Proteins; Renal Dialysis

Two previous short-term studies (12 weeks and up to 16 weeks) that used androgens to supplement recombinant human erythropoietin (rHuEPO) for the treatment of the anemia associated with end-stage renal disease showed divergent results. Both studies were limited by their brief duration, since the hematopoietic effect of androgens does not peak until 5 months. Therefore, we conducted a 6-month, prospective, randomized trial comparing low-dose rHuEPO alone and in combination with androgens for the treatment of the anemia of end-stage renal failure. Nineteen anemic chronic hemodialysis patients were randomized into two groups. Group A (n = 10) received 1,500 U rHuEPO intravenously three times a week for 26 weeks. Group B (n = 9) received the same dose of rHuEPO plus nandrolone decanoate 100 mg intramuscularly weekly. Baseline transferrin saturation, serum ferritin, intact serum parathyroid hormone, plasma aluminum, and hematocrit levels were not significantly different between the groups. At study completion, both groups showed a significant increase in mean hematocrit compared with baseline (group A: 24.8% +/- 1.4% to 28.3% +/- 2.8%, P = 0.003; group B: 25.1% +/- 1.5% to 33.2% +/- 4.5%, P = 0.001). The increase in hematocrit in the rHuEPO plus androgen-treated group was statistically greater than in the rHuEPO-alone group (8.2% +/- 4.4% v 3.5% +/- 2.8%; P = 0.012). With the exception of mild discomfort at the injection site, there were no significant side effects from nandrolone. We conclude that the combination of low-dose rHuEPO and nandrolone decanoate is effective treatment for the anemia of end-stage renal failure.

Topics: Anabolic Agents; Anemia; Drug Therapy, Combination; Epoetin Alfa; Erythropoietin; Female; Hematocrit; Humans; Kidney Failure, Chronic; Male; Middle Aged; Nandrolone; Nandrolone Decanoate; Prospective Studies; Recombinant Proteins; Renal Dialysis; Time Factors

Anemia in patients with chronic kidney disease (p-CKDs) may initiate or exacerbate left ventricular hypertrophy (LVH). This study aimed to determine whether treatment using long-acting erythropoietin-stimulating agents (L-ESAs) is independently associated with LVH during the pre-dialysis to maintenance dialysis period in p-CKDs.. Physical and laboratory examinations were performed 120 days before initiating dialysis in p-CKDs (baseline). To evaluate the left ventricular mass index (LVMI) after starting dialysis, the mean hemoglobin (Hb) was defined as the average at the start of dialysis and 6 months after starting dialysis. Changes in the LVMI were observed in three groups according to mean Hb levels (Hb < 10.1, 10.1 < Hb < 11.0, and Hb > 11.0 g/dL for Groups 1, 2, and 3, respectively). LVMI was evaluated using echocardiography at the pre-dialysis, initiation, and maintenance dialysis periods.. A lower LVMI at dialysis initiation and an improvement in LVMI were detected in the highest tertile group of mean Hb (11.0 g/dl). Consequently, in the high Hb group (Hb level > 11.0 g/dl), LVMI remained low from dialysis initiation until after 6 months.The relationship between Hb and LVMI was not significant; however, a constant correlation with β ≥ 0.4 in the absolute value was maintained.. L-ESAs may correlate with Hb and LVMI after administration, independent of the baseline LVMI and Hb values. These findings have therapeutic implications in the treatment strategies for p-CKDs during the pre-dialysis to maintenance dialysis period.

Topics: Anemia; Dialysis; Epoetin Alfa; Erythropoietin; Hemoglobins; Humans; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Longitudinal Studies; Renal Dialysis; Renal Insufficiency, Chronic; Retrospective Studies

This study was conducted to evaluate whether the efficacy and safety profile of recombinant human erythropoietin (rhEPO) manufactured by Daewoong Pharmaceutical Co., Ltd was similar to biological products approved by the drug safety regulatory authority.. It was an open-label, randomized, comparative, parallel, multi-center study in hemodialysis patients with anemia. The reference product at an individualized dose 3 times a week was given in 4-8 weeks of titration period and hemoglobin (Hb) level was controlled to reach the range of 10-12 g/dL. Then, the subjects were randomly administered with reference or test product with the same dose regimen. The primary endpoints were to demonstrate the Hb level change between baseline and evaluation period in both treatment groups, while the secondary endpoints were the mean change in weekly dosage per kg body weight and the instability rate of Hb level during maintenance and evaluation period. The safety was evaluated based on the adverse events incidence.. There was no statistical difference in the change of Hb between test and reference (0.14 g/dL and 0.75 g/dL respectively, with p>0.05), also for the mean changes of weekly dosage between groups (1091.40 IU and 570.15 IU respectively, with p>0.05). The instability rate of Hb in both test and reference was not statistically significantly different as well (26 and 15% respectively, with p>0.05).. This study proves that the efficacy indicated by the change instability of Hb and safety indicated by adverse event incidence of Epodion and the reference product on chronic kidney disease were similar.

Topics: Anemia; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Recombinant Proteins; Renal Insufficiency, Chronic; Treatment Outcome

In 2011, the Centers for Medicare & Medicaid Services implemented bundling of all services for patients receiving dialysis, including erythropoietin-stimulating agents use, and the Food and Drug Administration recommended conservative erythropoietin-stimulating agent dosing.. This retrospective cohort study investigated anemia care and clinical outcomes before and after the Centers for Medicare & Medicaid Services bundled payment and the revised Food and Drug Administration-recommended erythropoietin-stimulating agent labeling for Medicare-insured adults receiving hemodialysis using data from the United States Renal Data System from January 1, 2006 to December 31, 2016. Clinical outcomes included major adverse cardiovascular event (stroke, acute myocardial infarction, and all-cause mortality), cardiovascular mortality, and heart failure. Measurements were compared between prepolicy (2006-2010) and postpolicy (2012-2016) implementation using interrupted time series and Cox proportional hazards regression models.. The Medicare reimbursement policy and Food and Drug Administration-recommended erythropoietin-stimulating agent dosing changes were associated with lower erythropoietin-stimulating agent use and lower hemoglobin levels. These changes in anemia care were associated with lower risks of major adverse cardiovascular event, stroke, mortality, and heart failure but higher risk of acute myocardial infarction among adults receiving hemodialysis.

Topics: Adult; Aged; Anemia; Epoetin Alfa; Erythropoietin; Heart Failure; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Medicare; Myocardial Infarction; Policy; Renal Dialysis; Retrospective Studies; Stroke; United States

Shortened red blood cell (RBC) lifespan is one of the major factors contributing to anemia in end-stage renal disease (ESRD) patients and should be taken into account in anemia management protocols. In this study, we aimed to estimate RBC lifespan and the source of between-subject variability in ESRD patients. The resulting individual parameters (empirical Bayes estimates) were used to predict hemoglobin concentrations 2 weeks in advance. The reticulocyte-based estimation of RBC lifespan (REBEL) and the population modeling of RBC count data were used. A total of 120 blood samples collected biweekly over 10 weeks in 24 patients receiving maintenance doses of recombinant human erythropoietin (rHuEPO) subcutaneously were included in this analysis. Typical RBC lifespan was estimated to be 63.3 days. RBC lifespan was found to increase with erythroferrone, a recently identified hormone participating in iron metabolism. Approximately, a 10% increase in plasma erythroferrone was associated with a 5% increase in RBC lifespan. In addition, RBC lifespan was 18.7% shorter in females compared with males. Out of 24 subjects, 16 had hemoglobin concentrations predicted within 95% prediction intervals. The median absolute prediction error was 15.9% (interquartile range, 9.5 to 24.7%). We demonstrated that REBEL coupled with the population modeling technique can be used effectively to estimate RBC lifespan. Then, individual parameters can be used to predict future hemoglobin concentrations in ESRD patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Biomarkers; Epoetin Alfa; Female; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Peptide Hormones; Predictive Value of Tests; Prospective Studies; Reproducibility of Results; Reticulocyte Count; Reticulocytes; Time Factors; Treatment Outcome; Young Adult

The ability to control dosage regimens of erythropoiesis-stimulating agents (ESAs) to maintain a desired hemoglobin (HGB) target is still elusive. We utilized a Bayesian approach and informative priors to characterize HGB profiles, using simulated drug concentrations, in patients with end-stage renal disease receiving maintenance doses of epoetin alfa. We also demonstrated an adaptive Bayesian method, applied to individual patients, to improve the accuracy of HGB predictions over time. The results showed that sparse HGB data from daily clinical practice were characterized successfully. The adaptive Bayesian method effectively improved the accuracy of HGB predictions by updating the individual model with new data accounting for within-subject changes over time. The Bayesian approach presented leverages existing knowledge of the model parameters and has a potential utility in clinical practice to individualize dosage regimens of epoetin alfa and ESAs to achieve target HGB. Further studies are warranted to develop an application for practical use.

Topics: Adult; Aged; Aged, 80 and over; Algorithms; Anemia; Bayes Theorem; Dose-Response Relationship, Drug; Drug Development; Drug Discovery; Epoetin Alfa; Female; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Retrospective Studies

To compare the effectiveness of dynamic anemia management strategies by applying the parametric g-formula to electronic health records.. Patients with end-stage renal disease from the US Renal Data System who had congestive heart failure or ischemic heart disease and were undergoing hemodialysis in outpatient dialysis facilities between 2006 and 2010.. We explicitly emulated a target trial of three ‎erythropoietin dosing strategies (aimed at achieving a low, middle, or high hematocrit) and estimated the observational analog of the per-protocol effect.. Of 156,945 eligible patients, 41,970 died during the 18-month follow-up. Compared to the low-hematocrit strategy, the estimated risk of death was 4.6 (95% CI 4.4-4.9) percentage points higher under the high-hematocrit strategy and 1.8 (95% CI 1.7-1.9) percentage points higher under the mid-hematocrit strategy. The corresponding risk differences for a composite outcome of death and myocardial infarction were similar.. An explicit emulation of a target trial using electronic health records, combined with the parametric g-formula, allowed comparison of real-world dynamic strategies that have not been compared in randomized trials.

Topics: Anemia; Dose-Response Relationship, Drug; Electronic Health Records; Epoetin Alfa; Heart Failure; Hematocrit; Humans; Kidney Failure, Chronic; Myocardial Ischemia; Outcome and Process Assessment, Health Care; Randomized Controlled Trials as Topic; Renal Dialysis; Research Design

To assess real-world effectiveness and safety of intravenous (IV) HX575, a biosimilar epoetin-α, in hemodialysis (HD) patients.. This prospective, observational, pharmacoepidemiological study of adult HD patients treated with IV HX575 for renal anemia for up to 24 months was conducted in 114 centers in 10 European countries. Of 2,086 enrolled subjects (safety sample), 2,023 had ≥ 1 follow-up visit (effectiveness sample).. Most (59.3%) patients were male, median age was 68 years. At enrollment, most (82.5%) had been treated with an erythropoiesis-stimulating agent, and 73.0% had adequate iron stores. At baseline, mean (± standard deviation) baseline hemoglobin (Hb) was 11.09 (± 1.14) g/dL and HX575 dose 106.5 (± 78.7) international units (IU)/kg/week; at month 24, Hb was 11.25 (± 1.19) g/dL and HX575 dose 113.0 (± 102.5) IU/kg/week. Variations in mean HX575 dose and Hb over the study were not statistically significant. As to safety, 140 patients (6.7%) experienced ≥ 1 adverse event; of these, 19 events (16 patients; 0.8%) were related to HX575 treatment, 148 (108 patients; 5.2%) were reported as serious, including 12 events in 11 patients (0.5%) stated to be related. No cases of anti-epoetin antibodies or pure red cell aplasia were reported.. MONITOR-CKD5 confirmed the real-world effectiveness and safety profile of IV biosimilar HX575. HD patients treated for up to 24 months showed stable dosing patterns and Hb outcomes. The safety profile of HX575 is likewise comparable to reference epoetin-α.
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Topics: Aged; Anemia; Biosimilar Pharmaceuticals; Epoetin Alfa; Female; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Prospective Studies; Renal Dialysis

Topics: Aged; Anemia; Biomarkers; Drug Resistance; Epoetin Alfa; Female; Hematinics; Hemoglobins; Humans; Hyperparathyroidism; Kidney Failure, Chronic; Parathyroid Hormone; Parathyroidectomy; Renal Dialysis; Severity of Illness Index; Treatment Outcome

Hypothesizing that statins may be useful as adjuvant treatment for renal anemia, we examined the association between statin prescription (Rx) and erythropoiesis-stimulating agent (ESA) hyporesponsiveness in Japanese hemodialysis (HD) patients prescribed ESAs.. We examined 3,602 patients in 60 HD facilities dialyzed 3 times/week for ≥4 months from the Japan Dialysis Outcomes and Practice Patterns Study phases 3-5 (2005-2015). Statin Rx was reported at the end of a 4-month interval (baseline) for each patient. ESA hyporesponsiveness in the subsequent 4 months was then defined as a binary indicator (mean hemoglobin [Hgb] level <10 g/dL and mean ESA dose >6,000 units/week) and separately as the ESA resistance index (ERI; mean ESA dose/[dry weight × mean Hgb]). We used adjusted logistic and linear regressions to evaluate the associations between statin Rx and ESA hyporesponsiveness.. At baseline, 16.2% of patients reported statin Rx; 12.8% were classified as having ESA hyporesponsiveness during 4 months of follow-up. Compared to patients without statin Rx, patients with statin Rx had lower odds of ESA hyporesponsiveness (OR 0.87; 95% CI 0.66-1.15). Similarly, the ERI was lower for those with statin Rx than without (ratio of means, 0.94; 95% CI 0.89-0.99) after adjustment for possible confounders.. Our results suggest that statins may slightly reduce ESA hyporesponsiveness in HD patients. However, any causal inference is limited by the observational study design and unmeasured compliance with statin Rx.

Topics: Aged; Anemia; Cardiovascular Diseases; Chemotherapy, Adjuvant; Drug Resistance; Epoetin Alfa; Female; Hematinics; Hemoglobins; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Japan; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Random Allocation; Renal Dialysis; Treatment Outcome

In the general population, haemoglobin (Hb) concentration is higher in men than in women. However, target Hb levels in dialysis patients are set constant regardless of the patient's sex. The aim of this study was to evaluate Hb concentration and the use of erythropoiesis-stimulating agents (ESA) in peritoneal dialysis (PD) patients taking gender and dialysis adequacy into account.. The study comprised two parts. The first was a cross-sectional analysis of Hb and ESA in 2180 prevalent PD patients. The second included 88 incident PD patients, followed for 36 months. During this time, the major parameters recorded at 12-month intervals included: Hb concentration, weekly ESA, total, renal, and peritoneal Kt/V. Erythropoietin resistance index (ERI) was calculated as the ratio between ESA dose and achieved Hb.. In prevalent PD patients, Hb concentration was significantly lower in women, (11.2 ± 1.4 vs. 11.5 ± 1.6 g/dl; p < 0.001), despite higher doses of ESA (2691 ± 1821 vs. 2344 ± 1422; p = 0.001). Hb concentrations were related to dialysis adequacy in both cohorts. However, despite significantly higher Kt/V, women were characterized by a lower Hb level. In incident patients, this association was present throughout the observation period, while the ESA dose in women was significantly higher at every time point. In multiple regression analysis, gender was an independent determinant of ERI (b = 0.34; p < 0.05).. Despite higher dialysis adequacy, Hb concentration in women treated with PD is significantly lower, and the ability to correct it impaired, as compared to men.

Topics: Aged; Anemia; Cross-Sectional Studies; Epoetin Alfa; Female; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Peritoneal Dialysis; Prognosis; Registries; Retrospective Studies; Risk Assessment; Sex Factors; Treatment Outcome

Topics: Aged; Aged, 80 and over; Anemia; Anemia, Iron-Deficiency; Biosimilar Pharmaceuticals; Dose-Response Relationship, Drug; Drug Substitution; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Iron; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Retrospective Studies; Trace Elements

To evaluate the effect of erythropoietin (EPO) treatment on retinal nerve fiber layer (RNFL) parameters in patients with chronic renal failure (CRF) undergoing peritoneal dialysis (PD).. Fifty-eight eyes of 29 patients with CRF undergoing PD were evaluated. Fifteen patients have been treated with EPO (group 1), 14 patients without EPO treatment (group 2), and 30 eyes of 15 age-matched normal control subjects were assessed in group 3. A complete ophthalmologic examination and RNFL measurements were performed for each patient after PD. Anemia parameters were also measured. RNFL thickness protocol was used to acquire circular scans of 3.4 mm in diameter around optic nerve. RNFL thicknesses were evaluated in 4 quadrants. Only the left eyes were recruited for statistical analysis. The mean and quadrantal RNFL thickness values in group 1 were compared with those of groups 2 and 3.. The mean RNFL thickness values in patients undergoing PD were statistically lower than the control group at superior, inferior, nasal, and temporal quadrant, respectively (P=0.03, 0.04, 0.04, and 0.03). Differences between the RNFL thickness values in group 1 and group 2 were statistically significant only in the temporal quadrant (P=0.02).. In patients with CRF undergoing PD, RNFL thickness parameters were found to be significantly reduced. The effect of EPO on RNFL parameters was statistically significant only in the temporal quadrant.

Topics: Adult; Aged; Anemia, Iron-Deficiency; Epoetin Alfa; Erythropoietin; Female; Ferritins; Hematinics; Hemoglobins; Humans; Intraocular Pressure; Kidney Failure, Chronic; Male; Middle Aged; Nerve Fibers; Peritoneal Dialysis; Recombinant Proteins; Retinal Ganglion Cells; Transferrin; Young Adult

The aim of the US dialysis Prospective Payment System bundle, launched in January 2011, was reduction and more accurate prediction of costs of services, whilst maintaining or improving patient care. Dialysis facilities could either adopt the bundle completely (100%) in the first year of launch, or phase-in (25%) over four years. Differences in practice patterns and patient outcomes were hypothesized to occur in facilities that phased-in 25% compared to those that did not.. Data are from STEPPS, a study of 51 small dialysis organization facilities designed to describe trends in dialytic treatment before and after bundle implementation. Baseline was defined as October-December 2010; follow-up as January-December 2011. Facility- and patient-level data were collected at enrollment and regularly thereafter. Cox proportional hazards and linear multi-level models were used to estimate the effect of opting-in 25% (vs. 100%) on practice patterns and clinical outcomes.. 12 facilities (patient n = 346) opted-in 25% and 37 facilities (patient n = 1296) opted-in 100% to the dialysis bundle. At baseline, patients at 25% facilities were primarily covered by Medicare, were more likely to be black, and were receiving higher monthly epoetin alfa (EPO) doses. Throughout 2011, patients in 100% facilities received lower monthly EPO doses, and had lower mean hemoglobin concentrations; hospitalization and mortality rates were numerically lower in 25% facilities but not statistically different.. The economic pressure for dialysis providers to work within an expanded composite rate bundle whilst maintaining patient care may be a driver of practice indicator outcomes. Additional investigations are warranted to more precisely estimate clinical outcomes in patients attending facilities enrolling into the bundle 100% relative to the previous fee-for-service framework.

Topics: Adult; Aged; Ambulatory Care Facilities; Anemia; Epoetin Alfa; Female; Hematinics; Hospitalization; Humans; Kidney Failure, Chronic; Linear Models; Male; Middle Aged; Outcome Assessment, Health Care; Practice Patterns, Physicians'; Proportional Hazards Models; Prospective Payment System; Quality Indicators, Health Care; Renal Dialysis; United States

Adequately powered studies directly comparing hard clinical outcomes of darbepoetin alfa (DPO) versus epoetin alfa (EPO) in patients undergoing dialysis are lacking.. Observational, registry-based, retrospective cohort study; we mimicked a cluster-randomized trial by comparing mortality and cardiovascular events in US patients initiating hemodialysis therapy in facilities (almost) exclusively using DPO versus EPO.. Nonchain US hemodialysis facilities; each facility switching from EPO to DPO (2003-2010) was matched for location, profit status, and facility type with one EPO facility. Patients subsequently initiating hemodialysis therapy in these facilities were assigned their facility-level exposure.. DPO versus EPO.. All-cause mortality, cardiovascular mortality; composite of cardiovascular death, nonfatal myocardial infarction (MI), and nonfatal stroke.. Unadjusted and adjusted HRs from Cox proportional hazards regression models.. Of 508 dialysis facilities that switched to DPO, 492 were matched with a similar EPO facility; 19,932 (DPO: 9,465 [47.5%]; EPO: 10,467 [52.5%]) incident hemodialysis patients were followed up for 21,918 person-years during which 5,550 deaths occurred. Almost all baseline characteristics were tightly balanced. The demographics-adjusted mortality HR for DPO (vs EPO) was 1.06 (95% CI, 1.00-1.13) and was materially unchanged after adjustment for all other baseline characteristics (HR, 1.05; 95% CI, 0.99-1.12). Cardiovascular mortality did not differ between groups (HR, 1.05; 95% CI, 0.94-1.16). Nonfatal outcomes were evaluated among 9,455 patients with fee-for-service Medicare: 4,542 (48.0%) in DPO and 4,913 (52.0%) in EPO facilities. During 10,457 and 10,363 person-years, 248 and 372 events were recorded, respectively, for strokes and MIs. We found no differences in adjusted stroke or MI rates or their composite with cardiovascular death (HR, 1.10; 95% CI, 0.96-1.25).. Nonrandom treatment assignment, potential residual confounding.. In incident hemodialysis patients, mortality and cardiovascular event rates did not differ between patients treated at facilities predominantly using DPO versus EPO.

Topics: Aged; Ambulatory Care Facilities; Anemia; Cardiovascular Diseases; Cause of Death; Comorbidity; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemodialysis Units, Hospital; Humans; Kidney Failure, Chronic; Male; Middle Aged; Myocardial Infarction; Proportional Hazards Models; Recombinant Proteins; Registries; Renal Dialysis; Renal Insufficiency, Chronic; Retrospective Studies; Stroke; Treatment Outcome; United States

Recent changes in clinical practice guidelines and reimbursement policies may have affected the use of anemia-related medications and red blood cell (RBC) transfusions in peritoneal dialysis (PD) and hemodialysis (HD) patients. We sought to compare patterns of erythropoiesis-stimulating agents (ESA) and intravenous (IV) iron use, achieved hemoglobin levels, and RBC transfusion use in PD and HD patients.. In quarterly cohorts of prevalent dialysis patients receiving persistent therapy (>3 months), 2007-2011, with Medicare Parts A and B coverage, we assessed ESA and IV iron use and dose, RBC transfusions, and hemoglobin levels. Quarterly transfusion rates were calculated.. Observable PD and HD patients numbered 14,958 and 221,866 in Q1/2007 and 17,842 and 256,942 in Q4/2011. Adjusted ESA use was lower in PD (71.4-80.1%) than in HD (86.9-92.0%) patients, decreasing from 80.1% (Q1/2010) to 71.4% (Q4/2011) in PD patients, and from 92.0 to 86.9% in HD patients. The mean adjusted ESA dose decreased by 67.5% in PD and 58.4% in HD patients. IV iron use tended to increase, peaking at 39.3% for PD (Q3/2011) and 80.5% for HD (Q2/2011) patients. Adjusted mean hemoglobin levels fell from 11.7 to 10.6 mg/dl in PD and from 12.0 to 10.7 mg/dl in HD ESA users; adjusted transfusion rates increased from 2.4 to 3.0 per 100 patient-months in PD and from 2.6 to 3.3 in HD patients.. In patients receiving persistent dialysis, dose and frequency of ESA administrations decreased during the period 2007-2011. Mean hemoglobin levels decreased by more than 1 g/dl, while transfusion rates increased by approximately 25%.

Topics: Adolescent; Adult; Aged; Anemia; Cohort Studies; Epoetin Alfa; Erythrocyte Transfusion; Female; Hematinics; Hemoglobins; Humans; Iron; Kidney Failure, Chronic; Male; Middle Aged; Peritoneal Dialysis; Practice Patterns, Physicians'; Renal Dialysis; Retrospective Studies; Young Adult

Recombinant human erythropoietin (epoetin) is used routinely to increase blood hemoglobin levels in patients with ESRD and anemia. Although lower doses of epoetin are required to achieve equivalent hemoglobin responses when administered subcutaneously rather than intravenously, standard practice has been to administer epoetin to patients on hemodialysis intravenously. Randomized trials of alternative epoetin treatment regimens in patients with kidney failure have shown that risks of cardiovascular complications and death are related to the dose levels of epoetin used. Therefore, given the dose-sparing advantages of subcutaneous epoetin administration, the possibility that treatment of patients on hemodialysis with subcutaneous epoetin might be associated with more favorable outcomes compared with intravenous treatment was investigated.. A retrospective cohort study of 62,710 adult patients on hemodialysis treated with either intravenous or subcutaneous epoetin-α and enrolled in the Centers for Medicare and Medicaid Services ESRD Clinical Performance Measures Project from 1997 to 2005 was carried out. Risks of death and/or hospitalization for cardiovascular complications (adverse composite event outcomes) during 2 years of follow-up were determined in relationship to epoetin dose and route of administration (intravenous versus subcutaneous) by multivariate Cox proportional hazard modeling adjusted for demographics and clinical parameters.. Epoetin doses used to achieve equivalent hemoglobin responses in study patients were, on average, 25% higher when epoetin was administered intravenously rather than subcutaneously (as expected). Moreover, adverse composite event outcomes were found to be significantly more likely to occur during follow-up for patients on hemodialysis managed with intravenous rather than subcutaneous epoetin (adjusted hazard ratio for adverse events within 1 year [intravenous versus subcutaneous] was 1.11 [95% confidence interval, 1.04 to 1.18]).. This study finds that treatment of patients on hemodialysis with subcutaneous epoetin is associated with more favorable clinical outcomes than those associated with intravenous epoetin treatment.

Topics: Administration, Intravenous; Aged; Anemia; Cardiovascular Diseases; Epoetin Alfa; Female; Heart Failure; Hematinics; Hemoglobins; Hospitalization; Humans; Injections, Subcutaneous; Kidney Failure, Chronic; Male; Middle Aged; Myocardial Infarction; Renal Dialysis; Retrospective Studies; Stroke; United States

Clinical guidelines recommend concurrent treatment of anemia in end-stage renal disease with erythropoiesis-stimulating agents (ESAs) and iron. However, there are mixed data about optimal iron supplementation. To help address this gap, the relationship between iron markers and hemoglobin (Hb) response to ESA (Epoetin alfa) dose was examined. Electronic medical records of 1902 US chronic hemodialysis patients were analyzed over a 12-month period between June 2009 and June 2010. The analysis included patients who had at least one Hb value during each 4-week interval for four consecutive intervals (k - 2, k - 1, k, and k + 1; k is the index interval), received at least one ESA dose during intervals k - 1 or k, had at least one transferrin saturation (TSAT) value at interval k, and at least one ferritin value during intervals k - 2, k - 1, or k. Effect modification by TSAT and ferritin on Hb response was evaluated using the generalized estimating equations approach. Patients had a mean (standard deviation) age of 62 (15) years; 41% were Caucasian, 34% African American, 65% had hypertension, and 39% diabetes. Transferrin saturation, but not ferritin, had a statistically significant (P < 0.05) modifying effect on Hb response. Maximum Hb response was achieved when TSAT was 34%, with minimal incremental effect beyond these levels. Of the two standard clinical iron markers, TSAT should be used as the primary marker of the modifying effect of iron on Hb response to ESA. Long-term safety of iron use to improve Hb response to ESA warrants further study.

Topics: Diabetes Mellitus; Electronic Health Records; Epoetin Alfa; Erythropoietin; Female; Ferritins; Hematinics; Hemoglobins; Humans; Hypertension; Kidney Failure, Chronic; Male; Models, Biological; Practice Guidelines as Topic; Predictive Value of Tests; Recombinant Proteins; Renal Dialysis; United States

Changes in anemia management practices due to concerns about erythropoiesis-stimulating agent safety and Medicare payment changes may increase patient risk of transfusion. We examined anemia management trends in hemodialysis patients and risk of red blood cell (RBC) transfusion according to dialysis facility-level hemoglobin concentration.. Retrospective follow-up study; 6-month study period (January to June), 3-month exposure/follow-up.. For each year in 2007-2011, annual cohorts of point-prevalent Medicare primary payer patients receiving hemodialysis on January 1 with one or more hemoglobin measurements during the study period. Annual cohorts averaged 170,000 patients, with 130,000 patients and 3,100 facilities for the risk analysis.. Percentage of facility patient-months with hemoglobin level<10 g/dL.. Patient-level RBC transfusion rates.. Monthly epoetin alfa and intravenous iron doses, mean hemoglobin levels, and RBC transfusion rates; percentage of facility patient-months with hemoglobin levels<10 g/dL (exposure) and patient-level RBC transfusion rates (follow-up).. Percentages of patients with hemoglobin levels<10 g/dL increased every year from 2007 (6%) to 2011 (~11%). Epoetin alfa doses, iron doses, and transfusion rates remained relatively stable through 2010 and changed in 2011. Median monthly epoetin alfa and iron doses decreased 25% and 43.8%, respectively, and monthly transfusion rates increased from 2.8% to 3.2% in 2011, a 14.3% increase. Patients in facilities with the highest prevalence of hemoglobin levels<10 g/dL over 3 months were at ~30% elevated risk of receiving RBC transfusions within the next 3 months (relative risk, 1.28; 95% CI, 1.22-1.34).. Possibly incomplete claims data; smaller units excluded; hemoglobin levels reported monthly for patients receiving epoetin alfa; transfusions usually not administered in dialysis units.. Dialysis facility treatment practices, as assessed by percentage of patient-months with hemoglobin levels<10 g/dL over 3 months, were associated significantly with risk of transfusions in the next 3 months for all patients in the facility, regardless of patient case-mix.

Topics: Aged; Anemia; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Insurance Coverage; Kidney Failure, Chronic; Male; Medicare; Middle Aged; Recombinant Proteins; Renal Dialysis; Retrospective Studies; Risk Assessment; United States

Few data have been reported on anemia management practices in hospital-based dialysis centers (HBDCs), which are uniquely different from other freestanding dialysis centers. Examining data from HBDCs would help determine if HBDCs and the general US dialysis population have similar trends related to how anemia is managed in dialysis patients.. Given recent changes in the prescribing information of erythropoiesis-stimulating agents (ESAs) and in end-stage renal disease-related health policy and reimbursement, this study describes trends in anemia management practices in HBDCs from January 2010 through March 2013.. Electronic medical records of 5404 adult hemodialysis patients in 50 US-based HBDCs were analyzed retrospectively. Patients included in the study cohort were aged ≥18 years and had at least 1 hemoglobin (Hb) measurement and 1 dose of an ESA between January 2010 and March 2013. End points included Hb concentration, darbepoetin alfa dosing, epoetin alfa dosing, and iron biomarkers (transferrin saturation and ferritin) and dosing.. From 2010 to 2013, mean monthly Hb levels declined from 11.4 to 10.7 g/dL; the percentage of patients with mean monthly Hb levels <10 g/dL increased from 11.3% to 24.4%; and the percentage of patients with mean monthly Hb levels >12 g/dL declined from 30.1% to 11.2%. The median darbepoetin alfa cumulative 4-week dose also declined 38.8%, and the weekly epoetin alfa dose declined 24%. From January 2010 to March 2013, the percentage of patients with transferrin saturation >30% increased from 35.8% to 43.6%, the percentage of patients with ferritin levels >500 ng/mL increased from 62.0% to 77.9%, the percentage of patients with ferritin levels ≥800 ng/mL increased from 28.9% to 47.3%, and the median cumulative 4-week intravenous iron dose increased 50%.. These study results support growing evidence that meaningful changes have occurred over the last 3 years in how anemia is clinically managed in US hemodialysis patients. Study limitations include that changes in patient clinical/demographic characteristics over time were not controlled for and that study findings may not be applicable to HBDCs that have different patient populations and/or do not use an electronic medical record system. Continuing to evaluate anemia management practices in HBDCs would provide additional information on the risks and benefits of anemia care. Consistent with national data, the findings from this study indicate that from 2010 to 2013, HBDCs modified anemia management practices for dialysis patients, as evidenced by reductions in mean monthly Hb levels and ESA dosing and by increases in iron biomarkers and dosing.

Topics: Adolescent; Adult; Aged; Anemia; Cohort Studies; Darbepoetin alfa; Disease Management; Epoetin Alfa; Female; Hematinics; Hemoglobins; Hospitals; Humans; Iron; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Retrospective Studies; Young Adult

Anemia is common in patients with advanced chronic kidney disease. Whereas the treatment of anemia in patients with end-stage renal disease (ESRD) has attracted considerable attention, relatively little is known about patterns and trends in the anemia care received by patients before they start maintenance dialysis or undergo preemptive kidney transplantation.. To determine the trends in anemia treatment received by Medicare beneficiaries approaching ESRD.. Closed cohort study in the United States using national ESRD registry data (US Renal Data System) of patients 67 years or older who initiated maintenance dialysis or underwent preemptive kidney transplantation between 1995 and 2010. All eligible patients had uninterrupted Medicare (A+B) coverage for at least 2 years before ESRD.. Time, defined as calendar year of incident ESRD.. Use of erythropoiesis-stimulating agents (ESA), intravenous iron supplements, and blood transfusions in the 2 years prior to ESRD; hemoglobin concentration at the time of ESRD. We used multivariable modified Poisson regression to estimate utilization prevalence ratios (PRs).. Records of 466,803 patients were analyzed. The proportion of patients with incident ESRD receiving any ESA in the 2 years before increased from 3.2% in 1995 to a peak of 40.8% in 2007; thereafter, ESA use decreased modestly to 35.0% in 2010 (compared with 1995; PR, 9.85 [95% CI, 9.04-10.74]). Among patients who received an ESA, median time from first recorded ESA use to ESRD increased from 120 days in 1995 to 337 days in 2010. Intravenous iron administration increased from 1.2% (1995) to 12.3% (2010; PR, 9.20 [95% CI, 7.97-10.61]). The proportion of patients receiving any blood transfusions increased monotonically from 20.6% (1995) to 40.3% (2010; PR, 1.88 [95% CI, 1.82-1.95]). Mean hemoglobin concentrations were 9.5 g/dL in 1995, increased to a peak of 10.3 g/dL in 2006, and then decreased moderately to 9.9 g/dL in 2010.. Between 1995 and 2010, older adults approaching ESRD were increasingly more likely to be treated with ESAs and to receive intravenous iron supplementation, but also more likely to receive blood transfusions.

Topics: Aged; Aged, 80 and over; Anemia; Blood Transfusion; Cohort Studies; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobin A; Humans; Incidence; Iron; Kidney Failure, Chronic; Medicare; Practice Patterns, Physicians'; Recombinant Proteins; Registries; Renal Insufficiency, Chronic; United States

Hepcidin may play a critical role in the response of patients with anemia to iron and erythropoiesis-stimulating agent therapy. To evaluate the factors affecting serum hepcidin levels and their relation to other indexes of anemia, iron metabolism and inflammation, as well as the dose of erythropoietin, we studied 80 maintenance hemodialysis (MHD) patients treated with recombinant human erythropoietin and their serum hepcidin levels were specifically measured by using a competitive enzyme-linked immunosorbent assay. In linear regression analysis, ferritin was found to be a significant predictor of hepcidin levels in all the study patients. In the absence of apparent inflammation, serum hepcidin levels correlated exclusively with ferritin levels in MHD patients, and it was also an independent marker of inflammation as highly sensitive C-reactive protein.

Topics: Adult; Aged; Anemia; Biomarkers; C-Reactive Protein; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Female; Ferritins; Hematinics; Hepcidins; Homeostasis; Humans; Inflammation Mediators; Iron; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Time Factors; Treatment Outcome

Epoetin therapy used to treat anemia among ESRD patients has cost Medicare ∼$40 billion. Since January 2011, epoetin has been reimbursed via a new bundled prospective payment system (PPS). Our aim was to determine changes in epoetin dosing and hematocrit levels in response to PPS by different types of dialysis providers.. Data from the USRDS were used to identify 187,591 and 206,163 Medicare-eligible ESRD patients receiving hemodialysis during January 2010 (pre-PPS) and December 2011 (post-PPS). Standardized weekly mean epoetin dose administered pre- and post-PPS and adjustment in dose (titration) based on previous hematocrit level in each facility was disaggregated by profit status, chain membership and size.. Major declines in epoetin use, dosing and achieved hematocrit levels were observed after PPS. Among the three largest dialysis chains, the decline in standardized epoetin dose was 29% at Fresenius, 47% at DaVita, and 52% at DCI. The standardized weekly epoetin dose among profit and nonprofit facilities declined by 38 and 42%, respectively. Changes in titration patterns suggest that a new hematocrit target of 30-33% was in place after PPS, replacing the erstwhile 33-36% hematocrit target used before PPS.. Historically, important differences in anemia management were evident by dialysis organizational status. However, the confluence of financial incentives bundling epoetin payments and mounting scientific evidence linking higher hematocrit targets and higher epoetin doses to adverse outcomes have culminated in lower access to epoetin and lower doses across all dialysis providers in the first year after PPS.

Topics: Ambulatory Care Facilities; Anemia; Drug Therapy; Epoetin Alfa; Erythropoietin; Hematinics; Hematocrit; Humans; Kidney Failure, Chronic; Medicare; Ownership; Prospective Payment System; Recombinant Proteins; Renal Dialysis; United States

The aim was to compare the clinical efficacy of recombinant human erythropoietin (rHuEPO) and darbepoetin alpha (DA) in the treatment of anemia in children with chronic kidney disease (CKD).. Thirty-four (13 female, 21 male) CKD patients were enrolled in the study. Mean age was 11.42 ± 4.05 years. Nine patients were on hemodialysis, 18 were on peritoneal dialysis and seven patients were in CKD stage 4.. Seventeen patients received rHuEPO and the remaining 17 patients received DA. Hemoglobin (Hb) was not significantly different between the two groups during monthly follow up and at the end of 6 months (P > 0.05), but there was a significant increase within each group at the end of 6 months (P = 0.01 for rHuEPO; P = 0.02 for DA). Hb was not different between the patients on and not on dialysis in both groups at the end of the study (P > 0.05). The efficacy of the s.c. and i.v. routes was similar within each group (P > 0.05). Systolic hypertension was observed in only one patient in the DA group, no other adverse effect was observed in either groups.. DA is a reasonable alternative to rHuEPO in the treatment of anemia in pediatric CKD patients, due to its clinical efficacy, convenience of use, patient compliance and tolerability.

Topics: Adolescent; Anemia; Child; Child, Preschool; Darbepoetin alfa; Dose-Response Relationship, Drug; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Follow-Up Studies; Hematinics; Hemoglobinometry; Humans; Kidney Failure, Chronic; Male; Peritoneal Dialysis; Recombinant Proteins; Renal Dialysis; Retrospective Studies

Topics: Anemia; Blood Transfusion; Centers for Medicare and Medicaid Services, U.S.; Clinical Trials as Topic; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Practice Guidelines as Topic; Precision Medicine; Quality of Life; Recombinant Proteins; Renal Dialysis; United States; United States Food and Drug Administration

Topics: Epoetin Alfa; Erythropoietin; Humans; Kidney Failure, Chronic; Recombinant Proteins; Red-Cell Aplasia, Pure; Renal Insufficiency, Chronic

In a setting with two concurrent treatments, inverse-probability-of-treatment weights can be used to estimate the joint treatment effects or the marginal effect of one treatment while taking the other to be a confounder. We explore these two approaches in a study of intravenous iron use in hemodialysis patients treated concurrently with epoetin alfa (EPO).. We linked US Renal Data System data with electronic health records (2004-2008) from a large dialysis provider. Using a retrospective cohort design with 776,203 records from 117,050 regular hemodialysis patients, we examined a composite outcome: mortality, myocardial infarction, or stroke.. With EPO as a joint treatment, inverse-probability-of-treatment weights were unstable, confidence intervals for treatment effects were wide, covariate balance was unsatisfactory, and the treatment and outcome models were sensitive to omission of the baseline EPO covariate. By handling EPO exposure as a confounder instead of a joint treatment, we derived stable weights and balanced treatment groups on measured covariates.. In settings with concurrent treatments, if only one treatment is of interest, then including the other in the treatment model as a confounder may result in more stable treatment effect estimates. Otherwise, extreme weights may necessitate additional analysis steps.

Topics: Anemia; Confounding Factors, Epidemiologic; Drug Therapy, Combination; Epidemiologic Methods; Epoetin Alfa; Erythropoietin; Ferric Compounds; Hematinics; Humans; Kidney Failure, Chronic; Medicare; Myocardial Infarction; Outcome Assessment, Health Care; Recombinant Proteins; Renal Dialysis; Stroke; Transferrin; United States

Prior longitudinal observational studies have examined the practice patterns and outcomes of anaemia management, including the use of erythropoiesis-stimulating agents (ESAs). Several dimensions of effectiveness remain unaddressed; especially considering the revised ESA label (target Hb levels between 10 and 12 g/dL), the recently published TREAT study, and the European approval of the first ESA biosimilar (HX575). Anecdotal evidence suggests that patient outcomes are influenced by physician-related variables and whether anaemia management is congruent with practice guidelines, but this has not been studied systematically. MONITOR-CKD5 is an international, prospective, observational, pharmacoepidemiological study evaluating the multi-level factors and outcomes of treatment with HX575 for renal anaemia in haemodialysis patients. Driven by a novel, integrated, multi-focal framework for post-approval observational studies, it examines determinants of response at both the patient and the physician level; integrates an advocated statistical methodology here to fore used mainly in the social and behavioural sciences; assesses factors potentially predictive of a poor treatment response; and evaluates the extent to which treatment is congruent with evidence-based guidelines, good practice evidence, and the revised ESA label. This pan-European study will recruit at least 1,000 patients from a minimum of 75 centres, and follow them for up to 24 months following initiation of anaemia management with biosimilar epoetin alfa. MONITOR-CKD5 will not only study the core issues addressed by prior observational studies but also aims to take knowledge discovery a step further by assessing outcomes across varying cohorts of patients, and examining the impact of evidence-based practice on clinical outcomes, differentiating, in the process, between physician-level and patient-level determinants.

Topics: Adult; Anemia; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Kidney Failure, Chronic; Male; Pharmacoepidemiology; Predictive Value of Tests; Prospective Studies; Recombinant Proteins; Renal Dialysis; Treatment Outcome

Anemia in chronic renal failure results from inadequate production of erythropoietin and decrease in its biological activity, and the reduced activity of erythropoietin is caused by the presence of plasma inhibitors of erythropoietin. It is reported that one of the inhibitors of erythropoietin is cyanate, a potential uremic toxin formed spontaneously from increased urea due to decreased renal function, and erythropoietin loses its biological activity due to negatively charged cyanate. The purpose of this study is to investigate the protective effects of amino acids, positively charged amino groups, and albumin binding of several toxins on erythropoietin carbamoylation.. The degree of change in erythropoietin structure by cyanate was measured by the trinitrobenzenesulphonate reaction and Western blotting. The loss of biological activity of erythropoietin caused by cyanate was measured by injecting erythropoietin into rats with chronic renal failure.. The free amino groups in erythropoietin decreased under cyanate treatment in a time- and concentration-dependent manner. In the cyanate treatment group, of the twenty amino acids, phenylalanine, valine, tryptophan, threonine, and lysine prevented the structural modification of erythropoietin, according to Western blot analysis. In addition, of the three proteins, albumin prevented the structural modification of erythropoietin. As for the cyanate with erythropoietin treatment group, only lysine and albumin prevented the loss of biological activity of erythropoietin in the rats.. The results of this study suggest that lysine and albumin may play a protective role against renal anemia by erythropoietin carbamoylation in chronic renal failure.

Topics: Albumins; Amino Acids; Anemia; Animals; Cyanates; Epoetin Alfa; Erythropoietin; Kidney Failure, Chronic; Male; Rats; Rats, Sprague-Dawley; Recombinant Proteins

Topics: Anemia; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Kidney Failure, Chronic; Male; Recombinant Proteins

The management of anaemia in chronic kidney disease (CKD) to achieve current guideline goals is difficult and is hindered by multiple factors, including problems with the scheduling and adjustment of dosing of erythropoiesis-stimulating agents (ESAs) and the frequency of required ESA administration to achieve target haemoglobin (Hgb) levels.. The primary objective of this study was to examine whether converting a large cohort of CKD patients receiving epoetin alfa to darbepoetin alfa would decrease the frequency of drug administration while permitting an acceptable management of CKD-related anaemia.. In this retrospective cohort study of practice in a community-based CKD anaemia clinic, we evaluated the effects of conversion of a baseline group of 283 patients from epoetin alfa to darbepoetin alfa with a goal of decreasing the frequency of ESA administration while maintaining Hgb levels within a target range. The study observation period extended for 15 months after the initial conversion. An additional 256 CKD patients were started on darbepoetin alfa during the observation period and the frequency of their injections and the range of their Hgb levels were also monitored.. Following the conversion to darbepoetin alfa, we were able to increase the number of patients on once-monthly injections from 21% to 76% while keeping Hgb levels in the target range and maintaining stable blood pressure control. The mean number of ESA injections/patient/month decreased from 2.1 to 1.3.. In a community-based CKD anaemia clinic, conversion from epoetin alfa to darbepoetin alfa resulted in a decreased frequency of injections needed to maintain Hgb levels within an accepted target range.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Community Health Centers; Darbepoetin alfa; Dose-Response Relationship, Drug; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Retrospective Studies

To analyse the impact of dosing decisions for continuous erythropoietin receptor activator (C.E.R.A.), a continuous erythropoietin receptor activator.. This was a prospective, multicentre, single-arm study in haemodialysis patients receiving epoetin alfa/beta or darbepoetin alfa. After a 2-month screening phase, patients were converted to monthly C.E.R.A. using pre-filled syringes during a 5-month titration phase and a 2-month evaluation phase.. Four hundred and twenty-four eligible patients were converted to C.E.R.A. Mean Hb were 11.7 ± 0.7, 11.7 ± 0.8 and 11.5 ± 0.8 g/dl during screening, titration and evaluation, respectively. C.E.R.A. starting dose was 125 μg (n = 311) or 200 μg (n = 106), with corresponding final doses of 129 ± 61 μg and 203 ± 58 μg. The mean number of C.E.R.A. dose decreases and increases were 0.9 ± 1.0 and 1.1 ± 1.0 per patient, respectively. Hb rarely exceeded 12.5 g/dl after a C.E.R.A. dose increase (< 8%) and remained ≥ 11 g/dl after a dose reduction on approximately three-quarters of occasions. Among the 53 occasions where Hb decreased ≥ 2 g/dl between two consecutive visits, the previous dose had been withheld (n = 9), concomitant blood loss, coagulopathy or infection was present (n = 13), or iron parameters were low (n = 17). There were 104 adverse events/month during screening, and 45/month during the titration/evaluation phases. Serious adverse events occurred in 18.0 and 21.0 patients/month during the screening and titration/evaluation phases, respectively.. Switching haemodialysis patients from shorter-acting ESA to once-monthly C.E.R.A. using pre-filled syringes is straightforward, and Hb levels remain stable. Starting dose recommendations and dose changes correlated well with the clinical setting. Collateral factors such as infection or aggravating concomitant medical conditions should be taken into account.

Topics: Adult; Aged; Aged, 80 and over; Darbepoetin alfa; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Polyethylene Glycols; Prospective Studies; Recombinant Proteins; Renal Dialysis; Young Adult

Topics: Anemia; Epoetin Alfa; Erythropoietin; Germany; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Recombinant Proteins; Renal Dialysis

In May 2009 for financial reasons, the epoetin product used for hemoglobin (Hb) maintenance in our renal dialysis unit was changed from epoetin beta to epoetin alfa. Although widely believed that the dosage requirements are the same, we undertook a retrospective analysis to investigate whether the dosage requirements in chronic renal failure patients were comparable for both preparations. We studied 128 stable end-stage renal failure patients on hemodialysis (three times per week) receiving erythropoietin therapy to maintain their Hb at 11-12.5 g/dL. Patients were excluded if within the study period they developed signs of infection, bleeding, required blood transfusion, were under-dialyzed, or required hospital admission. Regular monthly Hb concentrations and hematocrit (Hct) levels were measured for each patient. The weekly EPO index (defined as weekly epoetin dose/mean monthly Hct) was derived for each patient, before and after regime change. Of the 128 patients in end-stage renal failure, 79 were included in the study. There was no significant difference between the two preparations in terms of Hct level achieved (p = 0.15). However, the median weekly epoetin dose requirement increased from 6733 (range 750-30,000) IU/week to 9000 (250-30,667) IU/week (p < 0.001). EPO index similarly increased from 20,465 (2500-130,846) IU/week/% to 27,073 (729-98,937) IU/week/% (p < 0.001). Our study showed that a higher dose of epoetin alfa was needed to maintain target Hb concentration.

Topics: Anemia; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Recombinant Proteins; Renal Dialysis; Retrospective Studies

Randomized trials of hemoglobin targeting in chronic kidney disease suggest that erythropoiesis-stimulating agent (ESA) dosing increases mortality risk, but dosing intensity is confounded by hemoglobin concentration. Appropriately designed observational studies are needed to clarify the association of ESA dosing with mortality risk.. Using Medicare claims, we conducted a retrospective cohort study of mortality risk associated with epoetin alfa (EPO) dosing in prevalent hemodialysis patients (n = 137,918), 2000-2004. We used marginal structural modeling to account for time-varying confounding attributable to recent history of blood transfusion and catheter insertion for vascular access, hemoglobin, hospital admission and days, and intravenous iron dosing. We stratified mortality analyses according to hemoglobin level (<10, 10-10.9, 11-11.9, and ≥12 g/dl).. With adjustment for serial correlation in EPO dosing, hemoglobin, hospital admission and days, and intravenous iron administration were the strongest predictors of outpatient EPO dosing. With hemoglobin <10 g/dl, mean weekly EPO dose in a 3-month period was negatively associated with subsequent mortality risk. With hemoglobin 10-10.9 and 11-11.9 g/dl, EPO dose and mortality risk were associated in a U-shaped form. With hemoglobin ≥12 g/dl, mean weekly EPO dose >20,000 IU was positively associated with mortality risk.. ESA dosing may be directly associated with risk of death, but the nature of the association likely varies according to hemoglobin concentration. Small doses with hemoglobin ≤12 g/dl and large doses with hemoglobin ≥10 g/dl may both be associated with poor outcomes.

Topics: Adult; Aged; Cohort Studies; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Medicare; Middle Aged; Recombinant Proteins; Renal Dialysis; Retrospective Studies; Risk; Time Factors; Treatment Outcome; United States

Renal anemia is caused by a lack of erythropoietin and iron, and is associated with increased morbidity and mortality in patients with chronic kidney disease. Iron deficiency is more common than previously thought. Diagnosis of absolute and relative iron deficiency is difficult because of the lack of an ideal diagnostic method. Adequate supplementation of iron in patients with renal anemia at a certain percentage of patients corrects anemia, while the other reduces the required doses of erythropoesis stimulating agents (ESAs), which can reduce treatment costs. In Department of Dialysis of General Hospital Bjelovar we carried out a retrospective study about treating renal anemia with iron during 36 months in 67 patients on chronic hemodialysis program in a period from 2007. to 2010. Our goal was to see if we adequately treat renal anemia with iron and to show the connection between the level of hemoglobin (Hb), ferritin and transferrin saturation (TSAT). The average value of ferritin in the 36 months follow-up was 196.8mcg/l, TSAT 24.16%, 107.8 g Hb/l. We conclude that the elevation of ferritin and TSAT correlates with the increase of Hb values in patients with renal anemia. Ferritin and TSAT values in our center are above the minimum criteria recommended by guidelines, but not within the target values for the treated population.

Topics: Adult; Aged; Aged, 80 and over; Anemia, Iron-Deficiency; Epoetin Alfa; Erythropoietin; Female; Ferritins; Humans; Infusions, Intravenous; Iron; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis

Renal anemia is complication of chronic kidney disease. It is caused by crythropoietin deficency and is associated with adverse outcomes in CKD patients. Renal anemia should be treated with erythropoesis-stimulating agents (ESAs), supplementary iron, adequate dialysis, and if necessary with red blood cells transfusions. The main problem of treatment is how to determine target hemoglobin value and keep it within the constant range. Current guidelines recommend target hemoglobin level 110 - 120 g/l, but optimal value need to be adjusted for every patient individualy keeping in mind primary kidney disease, age, gender and comorbidities. In Department of Dialysis of General Hospital Bjelovar we carried out a retrospective study about treating renal anemia in 67 patients on chronic hemodialysis program during 36 months in a period from 2007. til 2010. We monitored hemoglobin, feritin, saturation of transferin (TSAT), dose of LSE, number of change in dosage and number of transfusion. Mean hemoglobin level was 107.8 g/l, feritin level 196.8 mcg/l, TSAT 24.16%, weekly dose of ESAs 5951.9 IU. in 53.7% patiens dose was changed 11 - 20 times during that period, and 34% of patiens was treated with at least 1 dose of transfusion of red blood cells. We conclude that better iron supplementation and moderately higher doses of FSAs correlate with higher hemoglobin value, and hemoglobin variations is still big problem in renal anemia treatment.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Epoetin Alfa; Erythropoietin; Female; Ferritins; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis

We present a case of a young girl with end-stage renal disease secondary to anti-glomerular basement membrane disease who was receiving maintenance peritoneal dialysis and developed pure red cell aplasia secondary to anti-erythropoietin (EPO) antibodies. This occurred 13 months after the initiation of EPO alfa therapy for anemia. Initially, the patient required intermittent red blood cell transfusions. After immunosuppressive therapy had been initiated with corticosteroids and cyclosporine, the EPO antibody levels decreased precipitously, associated with an increased level of endogenous EPO production. For the following 6 months, the patient maintained adequate (>10 g/dL) hemoglobin levels and did not require red cell transfusions.

Topics: Anemia; Antibodies; Child, Preschool; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Recombinant Proteins; Red-Cell Aplasia, Pure; Renal Dialysis; Time Factors; Treatment Outcome

Topics: Epoetin Alfa; Erythropoietin; Humans; Kidney Failure, Chronic; Recombinant Proteins; United States

The health-related quality of life (HRQOL) claims in the current Epoetin alfa label are based on the reanalyses of the exercise and physical function data from the Canadian Erythropoietin Study Group trial. The reanalysis was done to comply with the Food and Drug Administration's requirement of using statistical methods that are currently standard in evaluating clinical trial data. Presented here are HRQOL results associated with anemia. The Canadian Erythropoietin Study Group trial was a multicenter, double blind, randomized, placebo-controlled trial evaluating the effects of Epoetin alfa on HRQOL in anemic hemodialysis patients. A total of 118 patients who were 18-75 years old, on hemodialysis for >3 months, who had a hemoglobin <9.0 g/dL, and did not have coronary artery disease or diabetes mellitus, were randomized to either receive placebo (n=40), or receive intravenous Epoetin alfa to achieve a target hemoglobin of 9.5-11.0 g/dL (n=40) or a target of 11.5-13.0 g/dL (n=38). Patients were followed for 6 months. The two Epoetin alfa-treatment groups were combined for all analyses performed. This post hoc analysis was conducted using an intent-to-treat repeated measures mixed model analysis of variance using Bonferroni's multiplicity correction. The Epoetin alfa-treated group showed a statistically significant improvement in the Kidney Disease Questionnaire symptom of fatigue in comparison with placebo. Additionally, the change in hemoglobin at 2 months was correlated with change in fatigue, energy, shortness of breath, and weakness, but had minimal effect on depression. These analyses confirm previously reported results, which indicate that treating hemodialysis patients with an erythropoiesis-stimulating agent improves HRQOL.

Topics: Adult; Aged; Anemia; Canada; Data Interpretation, Statistical; Epoetin Alfa; Erythropoietin; Fatigue; Female; Health Status; Hematinics; Humans; Kidney Failure, Chronic; Male; Middle Aged; Placebos; Quality of Life; Randomized Controlled Trials as Topic; Recombinant Proteins; Renal Dialysis

Topics: Anemia; Diabetes Complications; Endpoint Determination; Epoetin Alfa; Erythropoietin; Heart Failure; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Recombinant Proteins

Recombinant human erythropoietin (rHuEpo) has revolutionized the management of renal anemia, significantly improving patient quality of life. Great attention has been paid lately on how to optimally use this potent anti-anemic agent. Aiming to overview anemic patient management with Epotin (Julphar's rHuEpo) according to the new guidelines, we included in the study anemic (hemoglobin [Hb]or=18 years who were of iron replete (transeferene saturation (TSAT)>or=20% and serum ferritin>or=100 microg/L) with no evidence of serious inflammation (c-reactive protein (CRP)<30 mg/L) on thrice-weekly hemodialysis. The mean age and dialysis duration of 50.8+/-17 and 3.8+/-2.8 years, respectively, included 88.6% (n=31) de novo patients in the corrective phase with no previous exposure to erythropoietin. Safety-efficacy parameters showed insignificant changes throughout the 4-month study period, including iron profile that was maintained according to Kidney Disease Outcome Quality Initiative guidelines. Efficacy parameters revealed a significant increase (P<.0001) of Hb levels from a baseline of 8.5+/-1.0 to 11.1+/-1.1. Targeting an absolute increase of 2.5 g/dL in Hb throughout 3 months of the study period resulted in a 90.3% success rate. There were no dropouts due to intolerance, whereas all the recorded adverse events were classified as unrelated to the test product. In conclusion, Epotin was clinically effective to correct and maintain Hb levels in ESKD anemic patients on maintenance hemodialysis within the current recommended range and with a satisfactory safety profile consistent with previous international reports.

Topics: Anemia; Combined Modality Therapy; Epoetin Alfa; Erythropoiesis; Erythropoietin; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Recombinant Proteins; Renal Dialysis

Patients with chronic renal failure (CRF) receive recombinant human erythropoietin (rhEPO) for the correction of anemia. However, rhEPO also has an immunomodulatory effect. Detailed changes of phenotype and function of CD4(+) T lymphocytes in CRF patients receiving rhEPO have not been reported yet; their study may bring insight into understanding of this immunomodulatory action of rhEPO. Two groups of CRF patients were included into the study: those treated; and those not receiving rhEPO. The expression of activation markers on CD4(+) lymphocytes was measured with flow cytometry, both ex vivo and in vitro. The kinetics of CD4(+) T lymphocytes proliferation was calculated using a dividing cells tracing method and numerical approach. Significantly higher percentages of CD4(+)CD95(+), CD4(+)HLA-DR(+) cells, and lower percentages of CD4(+)CD69(+) and CD4(+)CD28(+) cells were observed in both rhEPO-treated and untreated patients when compared with healthy controls. Changes in the proportions of CD4(+)CD28(+) and CD4(+)HLA-DR(+) subpopulations were dependent on the type of rhEPO, being more pronounced for rhEPObeta. CD4(+) lymphocytes from untreated patients exhibited decreased expression of CD28 and CD69 after stimulation in vitro, whereas the expression of these antigens on lymphocytes of rhEPO-treated patients was similar to that observed in healthy controls. Fewer CD4(+)CD28(+) T lymphocytes of untreated patients proliferated in vitro; these cells had longer G0-->G1 time, which negatively correlated with surface expression of CD28. Our study confirms that rhEPO treatment normalizes activation parameters of CD4(+) T lymphocytes and their proliferative capacity, which could explain earlier described immunomodulatory effects of rhEPO in patients suffering from CRF.

Topics: Adult; Aged; Antigens, CD; Antigens, Differentiation, T-Lymphocyte; CD28 Antigens; CD4-Positive T-Lymphocytes; CD40 Ligand; Cell Proliferation; Cells, Cultured; Epoetin Alfa; Erythropoietin; Female; Flow Cytometry; Hematinics; Humans; Immunologic Factors; Immunophenotyping; Kidney Failure, Chronic; Kinetics; Lectins, C-Type; Lymphocyte Activation; Male; Middle Aged; Phenotype; Recombinant Proteins; Renal Dialysis; Treatment Outcome

Anaemia management with erythropoiesis-stimulating agents (ESA) and i.v. iron replacement in haemodialysis patients poses several clinical challenges, including maintaining stable haemoglobin (Hb) levels within target ranges while achieving lowest effective ESA dose. This manuscript describes the effect of implementing proactive protocol-driven adjustments for iron and ESA in maintenance haemodialysis patients.. This was a cohort study of 46 satellite haemodialysis patients examined from 2004 to 2006 with protocol implementation in 2005. Baseline haemoglobin, transferrin saturations (TSAT), ferritin values and ESA administration were obtained during 2004. Follow-up data was collected in 2006 and compared to baseline values in reference to specified targets in the 2004 Caring for Australasians with Renal Impairment (CARI) guidelines.. Fifty-four percent of patients achieved haemoglobin targets during follow up versus 43% patients during baseline. Seventy-nine percent of patients achieved TSAT targets during follow up versus 67% patients during baseline. Ninety percent of patients achieved ferritin targets during follow up versus 75% patients during baseline. Odds ratios for values falling within target ranges during follow up compared to baseline were 1.63 (Hb: P = 0.037; 95% confidence interval (CI), 1.03-2.57), 1.90 (TSAT: P = 0.006; 95% CI, 1.20-3.01) and 3.72 (ferritin: P = 0.003; 95% CI, 1.57-8.83). There was a trend toward lower average ESA dose (P = 0.07).. This study demonstrates the successful implementation and efficacy of a proactive protocol for iron and ESA treatment in haemodialysis patients. Benefits include increased concordance with historical guideline targets and decreased haemoglobin variability. Improved iron status and optimizing ESA response allows for lower ESA doses, limiting both potential side-effects of ESA (hypertension) and the burgeoning costs of anaemia management.

Topics: Anemia; Biomarkers; Clinical Protocols; Cohort Studies; Community Health Centers; Darbepoetin alfa; Epoetin Alfa; Erythropoiesis; Erythropoietin; Ferric Compounds; Ferritins; Guideline Adherence; Hematinics; Hemoglobins; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Odds Ratio; Practice Guidelines as Topic; Recombinant Proteins; Renal Dialysis; Retrospective Studies; Time Factors; Transferrin; Treatment Outcome; Western Australia

Darbepoetin alpha is effective for renal anemia when epoetin is insufficient. We previously reported that the dose conversion ratio from epoetin alpha to darbepoetin alpha was 1:350.5 after 24 weeks of follow-up. This study assessed the conversion ratio in stable Japanese hemodialysis patients after 52 weeks.. A total of 104 hemodialysis patients who were stable on intravenous epoetin alpha were switched to intravenous darbepoetin alpha according to the 1:200 rule. Then they were followed for 52 weeks to assess changes of hemoglobin and the darbepoetin alpha dose.. Eighty-five patients completed the study. Their hemoglobin increased very rapidly during the first 8 weeks. The final conversion ratio was 1:286.6 at 52 weeks. Darbepoetin alpha showed similar efficacy in diabetics and non-diabetics. Patients switching from a high epoetin alpha dose (> or =4500 IU/week) had a higher conversion ratio compared with those switching from a low dose (<4500 IU/week).. The dose conversion ratio of 1:200 was unsuitable and led to a rapid increase of hemoglobin. A conversion ratio of 1:250 to 1:300 should be employed when switching from epoetin alpha to darbepoetin alpha in Japanese patients.

Topics: Aged; Anemia; Asian People; Biomarkers; Darbepoetin alfa; Diabetes Mellitus; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Dosage Calculations; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Japan; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Time Factors; Treatment Outcome

An elderly patient with pure red cell aplasia (PRCA) with antierythropoietin (anti-EPO) antibodies is described. PRCA due to alloimmunization is a rare and severe complication of recombinant human erythropoietin (rHu-EPO) therapy. Most reported patients with PRCA were cured primarily by immunosuppressive drug therapy. The patient in this case, however, did not want to receive any immunosuppressive drugs. Therefore, rHu-EPO injection was simply discontinued, the severe anemia gradually improved, and the hemoglobin approached normal range. This case is very rare and significant in that there have been few such elderly patients with rHu-EPO-induced PRCA in whom PRCA remission was achieved, with decreasing antibody titers, after cessation of rHu-EPO alone. Further cases are needed to assess how PRCA should be treated in patients with anti-EPO antibodies.

Topics: Aged, 80 and over; Antibodies, Neutralizing; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Recombinant Proteins; Red-Cell Aplasia, Pure

Inflammation in an ESRD patient may impact responsiveness to erythropoiesis-stimulating agent (ESA) therapy. We sought to investigate the association between C-reactive protein (CRP) levels and average per-administration epoetin alfa (EPO) dose over 3 months following a CRP measurement.. The study is a retrospective cohort study of hemodialysis patients >or=18 years of age receiving care at a Fresenius Medical Care-North America facility between 1 July 2000 and 30 June 2002 who had no history of peritoneal dialysis. All patients had >or=1 CRP measurement and >or=3 months of recorded information before the CRP measurement (entry period). We evaluated the association between CRP levels and average hemoglobin (Hb) and per-administration EPO dose over the 3 months following the CRP measurement.. We identified 1754 patients with a CRP measurement; mean age was 62.6 years (SD 14.1), 51.5% were male, 56.2% were white and the median CRP value was 2.04 mg/dL (20.4 mg/L). Patients in the upper CRP quartiles were more likely to be older, recently hospitalized; have a catheter vascular access; have lower albumin, Hb and transferrin saturation levels and greater EPO doses. In the subsequent 3 months, EPO doses but not Hb levels were significantly higher for patients in the highest CRP quartile [3.21 mg/dL (32.1 mg/L)] (P = 0.01).. Inflammation as measured by an elevated CRP level appears to be an independent predictor of greater ESA dose requirements. Patients with the highest CRP levels required significantly higher ESA doses to achieve comparable Hb levels even after controlling for potential confounding variables.

Topics: Adult; Aged; C-Reactive Protein; Cohort Studies; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Retrospective Studies; Treatment Outcome

Compared to the intravenous route, subcutaneous administration of epoetin requires lower dose and will be an attractive option for cost containment when bundling for dialysis is implemented. Hemoglobin variability defined as fluctuation of hemoglobin over time has not been well studied with respect to the route of administration.. 157 prevalent-hemodialysis subjects were analyzed from an open-label, randomized study that compared the intravenous to the subcutaneous route of epoetin with identical weight-based dosing algorithm. Hemoglobin variability was defined as the number of weeks hemoglobin is outside the target range of 10-11 g/dl. Sensitivity analysis was performed.. 78 subjects in the intravenous and 79 in the subcutaneous group entered the 24-week dose maintenance phase. Baseline covariates were similar in both groups except for the dose of epoetin (lower in subcutaneous) and dialysis vintage (longer in intravenous). Patients on subcutaneous epoetin were outside the target range more weeks (p = 0.04) and had higher standard deviation of hemoglobin (p = 0.01) compared to the intravenous group.. The subcutaneous route of epoetin was associated with modestly higher hemoglobin variability, probably reflecting greater sensitivity of the subcutaneous route and/or identical epoetin-dosing algorithm employed in both the arms. This study could serve as an important guide when bundling for dialysis services is implemented as switching from intravenous to subcutaneous administration is likely to occur.

Topics: Aged; Anemia; Cohort Studies; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Injections, Intravenous; Injections, Subcutaneous; Kidney Failure, Chronic; Male; Middle Aged; Randomized Controlled Trials as Topic; Recombinant Proteins; Renal Dialysis

Anemia management remains complicated in patients with endstage renal disease on hemodialysis. We wished to evaluate the effect of protocol adherence to EPO and intravenous iron dosing on achieving the desired range of hemoglobin levels.. A cohort of hemodialysis patients was studied to evaluate the rate of adherence to EPO and iron dosing protocols over a 5 month period. A database was completed to evaluate all known comorbidities, demographic factors, and facility issues that might affect hemoglobin levels. A logistic regression model was employed to evaluate the effect of adherence to the anemia protocols on the probability of achieving a hemoglobin level below, within or above the targeted range of 11-12.5 g/dl.. Among 2114 patients, we found that adherence to both the EPO and iron dosing protocol resulted in the greatest probability of achieving the target hemoglobin range (56 +/- 5% in anemia protocol adherent patients versus 42 +/- 7% in non adherent patients). This was predominantly due to a lowered risk of having above target hemoglobin levels rather than below. The use of the anemia protocols was associated with lower rates of hospitalization (9 +/- 0.7 visits/100 months in adherent group vs 15 +/- 2 in non adherent group) and lower utilization of both EPO and intravenous iron. Furthermore, patients in the adherent groups had less variability of their hemoglobin levels month by month, at least as judged by standard deviation.. Adherence to anemia protocols, as practiced in the dialysis units included in this cohort, may improve hemodialysis patients' ability to achieve target hemoglobin levels, and by avoiding above target hemoglobin values, lower drug utilization and reduce variability of hemoglobin levels.

Topics: Aged; Anemia; Clinical Protocols; Cohort Studies; Epoetin Alfa; Erythropoietin; Female; Hemoglobins; Humans; Iron; Kidney Failure, Chronic; Male; Middle Aged; Patient Compliance; Recombinant Proteins; Renal Dialysis; Retrospective Studies

In patients treated by maintenance hemodialysis the relationship to survival of hemoglobin level and administered epoetin-alfa and intravenous iron is controversial. The study aim was to determine effects on patient survival of administered epoetin-alfa and intravenous iron, and of hemoglobin and variables related to iron status.. The patients were 1774 treated by maintenance hemodialysis in 3 dialysis units in New York, NY from January 1998 to June, 2007. A patient-centered, coded, electronic patient record used in patient care enabled retrospective analysis of data collected prospectively. For survival analysis, patients were censored when transplanted, transferred to hemodialysis at home or elsewhere, peritoneal dialysis. Univariate Kaplan-Meier analysis was followed by multivariate analysis with Cox's regression, using as variables age, race, gender, major co-morbid conditions, epoetin-alfa and intravenous iron administered, and 15 laboratory tests.. Median age was 59 years, epoetin-alfa (interquartile range) 18,162 (12,099, 27,741) units/week, intravenous iron 301 (202, 455) mg/month, survival 789 (354, 1489) days. Median hemoglobin was 116 (110, 120)g/L, transferrin saturation 29.7 (24.9, 35.1)%, serum ferritin 526 (247, 833) microg/L, serum albumin 39.0 (36.3, 41.5) g/L. Survival was better the higher the hemoglobin, best with > 120 g/L. Epoetin-alfa effect on survival was weak but had statistically significant interaction with intravenous iron. For intravenous iron, survival was best with 1-202 mg/month, slightly worse with 202-455 mg/month; it was worst with no intravenous iron, only slightly better with > 455 mg/month. Survival was worst with transferrin saturation < or = 16%, serum ferritin < or = 100 microg/L, best with transferrin saturation > 25%, serum ferritin > 600 microg/L The effects of each of hemoglobin, intravenous iron, transferrin saturation, and serum ferritin on survival were independently significant and not mediated by other predictors in the model.. Long term survival of maintenance hemodialysis patients was favorably affected by a relatively high hemoglobin level, by moderate intravenous iron administration, and by indicators of iron sufficiency. It was unfavorably influenced by a low hemoglobin level, and by indicators of iron deficiency.

Topics: Adult; Aged; Anemia; Comorbidity; Drug Therapy, Combination; Epoetin Alfa; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Ferritins; Glucaric Acid; Hemoglobins; Humans; Infusions, Intravenous; Iron-Dextran Complex; Kaplan-Meier Estimate; Kidney Failure, Chronic; Male; Middle Aged; Proportional Hazards Models; Prospective Studies; Recombinant Proteins; Renal Dialysis; Retrospective Studies; Survival Analysis; Transferrin

The common finding that low achieved hemoglobin in observational studies and high target hemoglobin in randomized trials each were associated with increased mortality and high epoetin dosage has suggested the possibility that high epoetin dosage might explain the increased mortality risk.. We considered data from 18,454 patients who were >or=65 yr, were in the US Renal Data System, started hemodialysis in 2003, and survived 3 mo on dialysis. We estimated the association between cumulative average epoetin dosage and survival through the subsequent 9 mo by using inverse probability weighting to adjust for time-dependent confounding by indication.. Survival was similar throughout the entire follow-up period for the three hypothetical treatment regimens selected: Low dosage 15,000 U/wk, medium dosage 30,000 U/wk, and high dosage 45,000 U/wk. Compared with a cumulative average dosage of 20,000 to 30,000 U/wk, the estimated hazard ratio (HR; 95% confidence interval [CI]) was 0.90 (0.52 to 1.54) for <10,000, 0.84 (0.67 to 1.05) for 10,000 to <20,000 U/wk, 0.96 (0.76 to 1.21) for 20,000 to <40,000 U/wk, and 0.91 (0.67 to 1.22) for >40,000 U/wk. In contrast, conventional unweighted models, which do not adequately adjust for time-dependent confounding by indication, indicated an association between high cumulative average epoetin dosage and increased mortality.. Our findings suggest that, on average, epoetin dosages >30,000 U/wk do not confer additional harm or benefit in elderly hemodialysis patients.

Topics: Age Factors; Aged; Anemia, Iron-Deficiency; Biomarkers; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Models, Statistical; Recombinant Proteins; Renal Dialysis; Risk Assessment; Time Factors; Treatment Outcome; United States

The first copy of Eprex, a product containing epoetin alfa, has been marketed in France, under the name Binocrit.

Topics: Drug Approval; Epoetin Alfa; Erythropoietin; France; Humans; Kidney Failure, Chronic; Recombinant Proteins; Therapeutic Equivalency

Patients on hemodialysis receiving subcutaneous (s.c.) erythropoietin usually require a higher dose if switched to intravenous (i.v.) administration. The factors affecting this dose change are not clear.. From January 2003 to June 2004, patients on hemodialysis who were receiving s.c. erythropoietin were enrolled in this prospective observational study. The s.c. route was continued for the first 2 months and the average weekly dose of erythropoietin to maintain the target hematocrit from that period was the baseline dose. Patients were then switched to i.v. erythropoietin and followed for 6 months, with the dose adjusted monthly to maintain the hematocrit. Biochemistry data were collected throughout the study period.. After 6 months, the mean i.v. dose of erythropoietin in 179 patients was 50.9% higher than baseline. The 86 patients requiring a >50% increase had a significantly lower serum albumin than 93 patients with a <50% increase in dose (3.64 g/dl vs. 3.78 g/dl, p<0.005). Each 1 g/dl higher level of serum albumin was associated with a 1237-U lower dose increment (F = 12.47, p<0.001).. Serum albumin is significantly correlated with the increase in erythropoietin dose needed when switching from s.c. to i.v. administration in Taiwanese on hemodialysis.

Topics: Epoetin Alfa; Erythropoietin; Female; Ferritins; Hematocrit; Humans; Injections, Intravenous; Injections, Subcutaneous; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Serum Albumin; Transferrin

Topics: Epoetin Alfa; Erythropoietin; Humans; Kidney Failure, Chronic; Male; Middle Aged; Nephritis, Interstitial; Recombinant Proteins; Red-Cell Aplasia, Pure; Renal Dialysis

The target of renal anemia correction with erythropoietin stimulating agents (ESAs) has been traditionally set at a hemoglobin (Hb) level of 11 - 12 g/dL. However, a trend has arisen of progressively increasing the Hb level to beyond 12 g/dL. Recent randomized control trials (RCTs) on correction of renal anemia in chronic kidney disease patients found that normalization of anemia to above 13 g/dL was associated with negative outcome parameters, echoing a previous RCT that showed increased death and myocardial infarction risk after normalization of hemoglobin level in hemodialysis patients. The latest consensus is to limit Hb to a level not exceeding 13 g/dL during renal anemia correction with ESAs. Currently, there are three ESAs available commercially. The choice of ESA should consider safety of subcutaneous administration, cost-effectiveness, and dosing frequency, all of which may affect compliance with ESA administration. Early identification of, and an early search for the causes of hyporesponsiveness to, ESAs is needed to avoid unnecessary escalation in the dose of ESAs. These approaches will help to improve the cost-effectiveness of ESA therapy and permit early detection of hidden problems. The current definitions of hyporesponsiveness are far too stringent and should be reviewed.

Topics: Anemia; Cost-Benefit Analysis; Drug Monitoring; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobinometry; Hemoglobins; Humans; Iron; Kidney Failure, Chronic; Peritoneal Dialysis; Randomized Controlled Trials as Topic; Recombinant Proteins; Trace Elements; Treatment Outcome

Topics: Aged; Aged, 80 and over; Anemia; Cyclosporine; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Male; Recombinant Proteins; Red-Cell Aplasia, Pure

Topics: Animals; Apoptosis; Arginine; Endothelium, Vascular; Epoetin Alfa; Erythropoietin; Heme Oxygenase-1; Humans; Kidney Failure, Chronic; Nitric Oxide; Nitric Oxide Synthase; Recombinant Proteins; Renal Dialysis

Topics: Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Hematocrit; Humans; Kidney Failure, Chronic; Recombinant Proteins; Reimbursement Mechanisms; United States; United States Food and Drug Administration

Topics: Aged; Anemia; Causality; Chronic Disease; Cross-Over Studies; Double-Blind Method; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobinometry; Humans; Kidney Failure, Chronic; Quality of Life; Randomized Controlled Trials as Topic; Recombinant Proteins

Treatment of the anemia of chronic kidney disease (CKD) with erythropoiesis-stimulating agents (ESAs) has been intensely debated during the past 2 years. Treatment with ESAs has transformed the lives of millions of patients with CKD, with fewer blood transfusions and improved quality of life. However, randomized trials have suggested that targeting greater hematocrits/hemoglobin levels and/or exposure to high doses of ESAs is associated with a greater risk of cardiovascular complications and mortality. The US Food and Drug Administration has inserted a boxed warning for ESAs and, along with the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (KDOQI), decreased recommended target hemoglobin ranges for ESA therapy. The Centers for Medicare & Medicaid Services has decreased ESA dosing recommendations in the Medicare claims policy for ESAs. Managing the anemia of CKD in the era of the hemoglobin level and ESA controversy has required aiming for appropriate hemoglobin levels, using the lowest effective ESA dose, and better managing the problem of ESA hyporesponsiveness.

Topics: Anemia; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Medicaid; Medicare; Recombinant Proteins; United States; United States Food and Drug Administration

The conversion of patients on stable epoetin therapy to darbepoetin alpha is usually carried out according to the '1 microg darbepoetin =200 U epoetin' rule, which is based on the protein content of the two compounds. Since several observations have suggested that this conversion factor leads to an overestimate of the required darbepoetin dose, the present multicentre study was designed to assess the true conversion ratio by prospectively evaluating the change in darbepoetin alpha dose after conversion from epoetin, which was required to keep haemoglobin (Hb) stable.. Haemodialysis patients with stable Hb and maintained on either s.c. or i.v. epoetin (alpha or beta) were switched to intravenously administered darbepoetin alpha according to the 1:200 rule. Subjects treated with epoetin two or three times per week received one weekly dose of darbepoetin alpha, subjects on weekly epoetin received darbepoetin alpha every 2 weeks. For 20 weeks, darbepoetin alpha was changed every 2 weeks according to a pre-specified algorithm, if this was needed to keep Hb within +/-1.0 g/dl of each subject's individual baseline. Thereafter, patients entered a 4-week evaluation period.. One hundred ad thirty-two patients in 17 Swiss centres were enrolled and 100 completed the study throughout the evaluation period. While mean Hb was maintained stable between baseline and evaluation period (11.8+/-0.6 g/dl in both), the mean required darbepoetin alpha dose decreased from 34.7+/-2.1 to 26.0+/-1.8 microg (-25%, P<0.0001), yielding a mean final conversion ratio of 1:336. A dose decrease was observed in 56 patients, no dose change in 28 and an increase in 16 patients. Dose reduction strongly depended on baseline epoetin dose: no dose reduction was required for baseline epoetin doses <5000 U/week, whereas a 37% lower mean dose was necessary for baseline doses of 7000-10 000 U/week. The darbepoetin alpha dose reduction did not depend on the previous epoetin type (alpha or beta) or the previous epoetin administration route (i.v. vs s.c.).. The mean darbepoetin alpha dose needed to keep Hb stable in patients previously treated with epoetin is significantly lower than the equimolar dose. Although the equimolar 1:200 conversion ratio is appropriate for lower epoetin doses (<5000 IU/week), the darbepoetin dose for patients converting from >or=5000 IU of epoetin per week is more likely to follow a 1:250 to 1:350 conversion rule. If pricing is based on the 1:200 rule such as in Switzerland, this may translate into cost savings.

Topics: Aged; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Recombinant Proteins; Renal Dialysis

Nearly all dialysis patients receive epoetin therapy to treat anemia. Using the United States Renal Data System, we monitored the 14,001 patients aged 65 and older who started dialysis and epoetin treatment in 2003-2004. We estimated the dose-response relationship for the average epoetin dose and hematocrit during a 3-month initiation and subsequent 3-month maintenance phase using a marginal structural model to adjust for measured time-dependent confounding by indication. During the initiation phase, an S-shaped dose-response relationship for average weekly epoetin dose and hematocrit response was found. Average hematocrit levels rose as the epoetin dose was increased from 9,000 to approximately 22,500 units per week. At higher doses, the effect of increasing epoetin was minimal with average hematocrit levels plateauing at 38.5%, but this was less evident in the maintenance phase. Among patients who reached this phase, doses required to maintain the hematocrit level were lower than those required to achieve similar hematocrit levels in the initiation phase. The dose-response curve found in our study suggests that published recommendations for starting dose are appropriate, and a starting dose of 7,500-15,000 units per week can maintain the hematocrit level in the desired target range of 33-36%.

Topics: Aged; Aged, 80 and over; Anemia; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hematocrit; Humans; Kidney Failure, Chronic; Male; Models, Biological; Recombinant Proteins; Renal Dialysis

Patients with advanced chronic renal disease (CRD) suffer from excessive morbidity and mortality due to complications of accelerated atherosclerosis. Recombinant human erythropoietin (EPO), which is routinely used to treat the anaemia present in approximately 90% of dialysis-dependent patients with end-stage renal disease, may induce vascular dysfunction by reducing nitric oxide (NO) availability. Pathophysiologic concentrations of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), are found in patients with CRD and correlate with vascular disease and cardiovascular mortality. The aim of the current study was to investigate the effect of EPO on ADMA concentrations and NO generation in vitro and in vivo. Furthermore, we wanted to study the effect of EPO on the expression of the enzymes that regulate ADMA metabolism and NO generation.. Human umbilical vein endothelial cells (HUVECs) were exposed to therapeutic concentrations of EPO. The expression and metabolic activity of dimethylarginine dimethylaminohydrolase II (DDAH II), the enzyme that degrades ADMA, was evaluated. Following subcutaneous administration of EPO to Balb/c mice for 10 weeks, serum ADMA concentrations were determined. Systolic blood pressure was measured noninvasively. Urinary nitrite and nitrate (NOx) concentrations were assessed by Griess assay. Protein expression of DDAH and NOS in livers and kidneys was measured by western blotting.. EPO suppressed ADMA elaboration by HUVECs. Systolic blood pressure and serum concentrations of ADMA were significantly elevated in EPO-treated mice. The protein expression of DDAH I in the kidney and liver was upregulated while hepatic expression of DDAH II was decreased and renal DDAH II expression remained unchanged by EPO administration. However, EPO augmented urinary NOx concentrations as well as the expression of NOS 1 and NOS 2 in the kidney.. In spite of elevating serum ADMA concentrations, EPO does not appear to compromise overall NO generation in Balb/c mice.

Topics: Amidohydrolases; Animals; Arginine; Base Sequence; Cells, Cultured; DNA Primers; Endothelial Cells; Epoetin Alfa; Erythropoietin; Humans; Kidney; Kidney Failure, Chronic; Liver; Male; Mice; Mice, Inbred BALB C; Nitric Oxide; Nitric Oxide Synthase Type II; Recombinant Proteins; Up-Regulation; Vascular Diseases

Topics: Anemia; Epoetin Alfa; Erythropoietin; Follow-Up Studies; Heart Failure; Hematocrit; Humans; Kidney Failure, Chronic; Myocardial Infarction; Randomized Controlled Trials as Topic; Recombinant Proteins; Renal Dialysis; Survival Analysis

Our aim was to evaluate red blood cell (RBC) membrane protein composition in chronic kidney disease (CKD) stage 5 patients under haemodialysis (HD) and recombinant human erythropoietin (rhEPO) therapy, and its linkage to rhEPO hyporesponsiveness. We evaluated in 63 CKD stage 5 patients (32 responders and 31 non-responders to rhEPO therapy) and in 26 healthy controls RBC count, haematocrit, haemoglobin concentration, haematimetric indices, reticulocyte count, reticulocyte production index, RBC osmotic fragility test and membrane protein analyses. CKD stage 5 patients presented significant changes in membrane protein composition, namely a reduction in spectrin, associated to altered protein 4.1/spectrin and spectrin/band 3 ratios. Non-responder CKD stage 5 patients were more anaemic, with more microcytic and anisocytic RBCs, than responders; significantly altered ankyrin/band 3 and spectrin/ankyrin ratios were also observed. CKD stage 5 patients under HD are associated with an altered protein membrane structure, which seems to the disease itself and/or to the interaction with HD membranes.

Topics: Aged; Anemia; Anion Exchange Protein 1, Erythrocyte; Ankyrins; Blood Proteins; Darbepoetin alfa; Diabetic Nephropathies; Drug Resistance; Epoetin Alfa; Erythrocyte Membrane; Erythropoietin; Female; Folic Acid; Humans; Iron; Kidney Failure, Chronic; Male; Membrane Proteins; Membranes, Artificial; Middle Aged; Oxidation-Reduction; Recombinant Proteins; Renal Dialysis; Spectrin

Topics: Anemia; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Recombinant Proteins; Renal Dialysis

Topics: Anemia; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Recombinant Proteins; Renal Dialysis

Our objective was to determine whether patient factors, processes of care and measures of erythropoietin (EPO) responsiveness were associated with successful anemia management at the individual patient level.. We retrospectively reviewed laboratory and demographic data from 1499 patients receiving hemodialysis in 15 units operated by the same dialysis provider. We performed univariate and multivariate logistic regression analysis to determine predictors of an average 3-month hemoglobin level below or above the target interval of 11.0-12.5 g/dL. To explain the effect of facility on anemia performance, we calculated correlations between measures of EPO responsiveness and the probability of achieving the target interval by facility.. Patients above the target hemoglobin range demonstrated an association with parathyroid hormone (PTH) (OR = 0.96 per 100 pg/mL increase), female gender (OR = 0.68), EPO protocol use (OR = 0.94 per 10% increase in use) and facility (range of OR = 0.26-2.59 for 15 participating sites). Patients below the target hemoglobin range demonstrated an association with CRP (OR = 1.10 per mg/L increase), PTH (OR = 1.07 per 100 pg/mL increase), iron deficiency (OR = 1.07 per 10% increase), EPO protocol use (OR = 0.89 per 10% increase in use), iron protocol use (OR = 0.93 per 10% increase in use) and facility (range of OR = 0.58-3.41 over 15 units). EPO index (r = 0.71), EPO dose (r = 0.73), hemoglobin (r = -0.60) and EPO per unit weight (r = 0.76) were significantly correlated with the probability of achieving the target hemoglobin by facility.. The facility significantly influences the outcome of anemia management in patients with ESRD. In part, this is due to the patients' EPO responsiveness, which may be influenced by facility care patterns.

Topics: Anemia; C-Reactive Protein; Epoetin Alfa; Erythropoietin; Health Facilities; Hemoglobins; Humans; Kidney Failure, Chronic; Linear Models; Logistic Models; Odds Ratio; Organizations, Nonprofit; Recombinant Proteins; Renal Dialysis; Retrospective Studies

This study assessed the employer cost burden of predialysis CKD-related anemia for a major US manufacturer, by examining indirect and direct costs before and after initiation of epoetin alfa (EPO).. Hemoglobin (Hb) levels, direct costs, and indirect costs for employees with CKD-related anemia were collected for 15 months (9 months pre-EPO and 6 months concurrent/post-EPO treatment). Indirect costs (absenteeism and presenteeism) and direct costs (medical and pharmacy) were compared for the pre- and post-EPO treatment periods.. Treating CKD-related anemia with EPO increased Hb levels from 9.4 (1 to 3 months pre-EPO)to 12.2 g/dL (4 to 6 months post-EPO), decreased absenteeism by 52.3 days per patient per year (PPPY), increased productivity by 91.5% PPPY, and reduced health care costs by approximately $4417 PPPY.. Among employees with predialysis CKD-related anemia, EPO treatment was associated with increased Hb levels, improved productivity, and decreased direct employer costs.

Topics: Aged; Analysis of Variance; Anemia; Cohort Studies; Comorbidity; Deductibles and Coinsurance; Efficiency, Organizational; Employer Health Costs; Epoetin Alfa; Erythropoietin; Female; Health Services; Hematinics; Hemoglobins; Humans; Industry; Kidney Failure, Chronic; Male; Middle Aged; Occupational Health; Recombinant Proteins; United States

The paper describes the need for the introduction of an anaemia management algorithm. It discussed the problems which the unit had in constant reviewing and re-prescribing ESA to maintain optimum haemoglobin levels for the unit's patients. The method used to create and use the algorithm is explained. The findings demonstrate the beneficial effects of using the algorithm. The paper concludes with the recommendation that algorithms should be more widely used for better treatment outcomes.

Topics: Algorithms; Anemia; Clinical Protocols; Drug Administration Schedule; Drug Monitoring; Drug Prescriptions; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Medical Order Entry Systems; Medical Records Systems, Computerized; Nurse Clinicians; Nurse's Role; Nursing Assessment; Nursing Audit; Nursing Evaluation Research; Professional Autonomy; Recombinant Proteins; Registries; Renal Dialysis; Time Factors; United Kingdom

Topics: Epoetin Alfa; Erythropoietin; Health Care Reform; Health Expenditures; Health Services Misuse; Hemoglobins; Humans; Kidney Failure, Chronic; Medicare; Recombinant Proteins; Reimbursement Mechanisms; Renal Dialysis; United States

Topics: Anemia; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Observation; Prognosis; Randomized Controlled Trials as Topic; Recombinant Proteins

The aim of this study was to evaluate the impact of epoetin alfa (EPO) therapy on delaying progression to renal dialysis and quantify the associated medical cost savings in elderly chronic kidney disease (CKD) patients. Elderly (>/=65 years) dialysis patients who had >/=1 hemoglobin (Hb) value and >/=1 glomerular filtration rate (GFR) value of <60 mL/min/1.73 m(2) were identified using health claims and laboratory data from the period January 1999 to February 2005. Exclusion criteria included: organ transplantation, blood transfusion, use of darbepoetin alfa, and dialysis for reasons other than CKD. Each EPO patient was matched by Hb and GFR to one control patient. The time from when matched patients had the same GFR value to dialysis was compared. The economic impact of EPO on delaying dialysis was monetized using standardized health plan payments, and adjusted to 2005 United States dollars. Sixty-eight patients (34 EPO and 34 matched controls) formed the study population. The average time to dialysis was 156 days longer for the EPO group compared to the matched control group (p = 0.003). Analysis by CKD severity revealed that EPO therapy in less severe CKD patients offered a greater delay in time to dialysis (Stage 4: 213 days difference, p = 0.003; Stage 5: 104 days difference, p = 0.160). EPO treatment resulted in cost savings of $43,374-$59,222 per patient compared to non-EPO matched controls. This retrospective matched cohort study suggests that EPO therapy has a beneficial impact on delaying progression to dialysis in elderly CKD patients, especially in those with less severe CKD.

Topics: Aged; Comorbidity; Cost Savings; Disease Progression; Epoetin Alfa; Erythropoietin; Glomerular Filtration Rate; Hematinics; Humans; Kidney Failure, Chronic; Medicare; Models, Economic; Recombinant Proteins; Renal Dialysis; Retrospective Studies; Time Factors; United States

Topics: Anemia; Cardiovascular Diseases; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Recombinant Proteins; Renal Insufficiency, Chronic; Thromboembolism

Topics: Anemia; Clinical Trials as Topic; Darbepoetin alfa; Databases, Factual; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobins; Humans; Injections, Intravenous; Injections, Subcutaneous; Kidney Failure, Chronic; Recombinant Proteins; Renal Dialysis; Research Design; Treatment Outcome

To determine whether there is a change in the dose of epoetin alfa when switching from subcutaneous (SC) to intravenous (IV) administration in Australian haemodialysis patients.. Validated data from 2214 haemodialysis patients at 16 Australian hospitals who switched from SC to IV administration of epoetin alfa from January 2002 to September 2003 were extracted from the Renal Anaemia Management database provided by Janssen-Cilag. Of these patients, 806 had dosing data for at least 1 month before switch through to 6 months post switch (6 month cohort).. In the 6 month cohort, the mean dose was 10 776 IU/week (95% CI: 10 235, 11 317) at switch compared with 12 008 IU/week (95% CI: 11 447, 12 569) 6 months post switch, an increase in a dose of 1232 IU/week (95% CI: 868, 1596). The mean haemoglobin levels at switch were 11.55 g/dL (95% CI: 11.45, 11.66) compared with 11.59 g/dL (95% CI: 11.49, 11.68) 6 months after switch. Centre and dosing frequency of epoetin alfa before switch were determinants of increased dose.. Changing from SC to IV administration of epoetin alfa resulted in an 11% increase in mean dose to maintain haemoglobin levels in Australian haemodialysis patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Australia; Child; Cohort Studies; Databases, Factual; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Ferritins; Follow-Up Studies; Hematinics; Hemoglobins; Humans; Injections, Intravenous; Injections, Subcutaneous; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Time Factors; Transferrin; Treatment Outcome

The purpose of the present study was to determine whether Australian haemodialysis patients receiving intravenous epoetin alfa are comparable to those receiving darbepoetin alfa with respect to a range of demographic and clinical characteristics.. Data on haemodialysis patients were extracted from the Renal Anaemia Management database for the period from July 2003 to March 2004.. Patients on haemodialysis were more likely to receive epoetin alfa than to receive darbepoetin alfa (n = 1898 vs n = 603, respectively). Patients receiving epoetin alfa were marginally older than patients receiving darbepoetin alfa (61 +/- 15 vs 59 +/- 15, mean +/- SD; P < 0.05). Patients were similar in terms of proportion of males, incidence of diabetes, and angiotensin-converting enzyme inhibitor and antihypertensive use. However, patients receiving epoetin alfa had higher haemoglobin (116 +/- 13 g/L vs 113 +/- 15 g/L), serum ferritin (582 +/- 414 mug/L vs 461 +/- 350 mug/L) and transferrin saturation levels (29 +/- 13% vs 26 +/- 14%), and better dialysis adequacy test results, as measured by urea reduction ratio (URR) or Kt/V, than patients on darbepoetin alfa (P < 0.001 in all cases). The frequency of dosing was higher in the epoetin alfa group (1.7 +/- 0.7 doses/week vs 1.0 +/- 0.4 doses/week, P < 0.001). Using the 240:1 dose ratio recommended in the Australian prescribing information for darbepoetin alfa, epoetin alfa was administered at a lower dose compared with darbepoetin alfa (164 +/- 116 IU/kg per week vs 192 +/- 152 IU/kg per week, P < 0.001).. This cross-sectional sample of Australian clinical practice suggests that there are differences in the haematological parameters of patients receiving epoetin alfa compared with patients receiving darbepoetin alfa.

Topics: Adult; Aged; Anemia; Australia; Cohort Studies; Cross-Sectional Studies; Darbepoetin alfa; Databases, Factual; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Ferritins; Hematinics; Hemoglobins; Humans; Injections, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Renal Dialysis; Transferrin; Treatment Outcome

Topics: Ambulatory Care Facilities; Anemia; Drug Utilization; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Ownership; Recombinant Proteins; Renal Dialysis; United States

Anemia is one of most common complications in end stage renal disease (ESRD) patients. Erythropoietin has been recommended for treatment of anemia in these patients.. To evaluate the clinical efficacy, safety and usefulness of newly imported erythropoietin, called Espogen, usage in ESRD undergoing hemodialysis.. An open, non-comparative, prospective study of administered Espogen was conducted in 30 ESRD patients undergoing hemodialysis for a 12 week period. Eligible criteria included hemoglobin of less than 8 g%, hematocrit of less than 25% for at least three consecutive months with a serum ferritin of more than 100 ng%. Initial dose of drug was 150 units/kg/week subcutaneously, two or three times a week and dosage was adjusted to maintain the Hb at 10-12g%.. In 28 patients, hemoglobin and hematocrit were increased significantly from 7.1 +/- 1.14 g/dl and 22.1 +/- 3.24% at baseline to 10.1 +/- 1.49 g/dl and 31.7 +/- 4.01% at the end of the study period respectively (p < 0.05). Mean weekly of Espogen dosage was 8390 +/- 2452.7 IU/week, which was 152.1 IU/kg/week. Some patients could reduce the dose at week 10. Reticulocyte increased significantly from 0.69 +/- 0.58% at baseline to highest value, 1.41 +/- 0.74 at 2 week and 1.30 +/- 0.66 at the end of the present study. Serum vitamin B12, serum folate, and red blood cell folate were not significantly changed. However serum ferritin decreased significantly from 840.6 +/- 948.95 to 582.7 +/- 990.70 ng/ml (p < 0.05). General condition including SF-36 score and tiredness were improved. There were no significant adverse events except mean arterial blood pressure of pre dialysis value which was statistically significant increased at the end of the present study (from 101.0 +/- 17.65 at week 0 and 110.4 +/- 16.8 mmHg at week 12, p = 0.0223).. This clinical study showed that Espogen has proven effective and safe for treatment of anemia in hemodialysis patients. No serious adverse events occurred during the study period.

Topics: Anemia; Blood Pressure; Epoetin Alfa; Erythropoietin; Female; Ferritins; Hematinics; Humans; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Renal Dialysis; Treatment Outcome

The National Kidney Foundation (NKF) clinical practice recommendations for treating anemia in chronic kidney disease (CKD) and the dosing, route and frequency of administration, efficacy, and safety of currently available and investigational drug therapies for anemia in patients with CKD, including the erythropoietin-stimulating agents (ESAs) iron replacement, and adjuvants, are described.. The NKF recommendations for ESA use are general and include dosing based on the measured and target hemoglobin concentrations, the rate of increase in hemoglobin, and clinical circumstances, with the route and frequency of administration determined by the CKD stage, treatment setting, efficacy, and ESA class. A serum ferritin concentration of 100-500 ng/mL is the target during oral and intravenous (i.v.) iron therapy for predialysis and peritoneal dialysis patients, but use of the i.v. route of administration and a target serum ferritin concentration of 200-500 ng/mL is recommended for hemodialysis patients by NKF. Iron deficiency and inflammation are possible causes of inadequate response to ESAs. The safety profile of epoetin alfa and darbepoetin alfa are similar, but the longer half-life of darbepoetin alfa permits administration on a once-monthly basis in patients with CKD and anemia. Extended dosing of CERA also appears safe and effective in dialysis patients with CKD. Several investigational anemia therapies with a variety of mechanisms of action are in development.. Efforts by the NKF to update their clinical practice recommendations provide clinicians with insight into the optimal therapeutic approach to treating anemia in patients with CKD. Clinical research has resulted in the development of new therapeutic modalities to improve outcomes in patients with CKD and anemia.

Topics: Anemia; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Ferritins; Hematinics; Hemoglobins; Humans; Iron; Kidney Failure, Chronic; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Recombinant Proteins; Renal Dialysis

Treatment of anemia in hemodialysis patients usually requires the use of expensive erythropoietic proteins. Cost analyses usually focus on drug acquisition costs. Other costs associated with anemia therapy include resources for anemia monitoring as well as preparation and administration of an erythropoiesis-stimulating agent.. The nonacquisition costs associated with subcutaneous administration of epoetin alfa were determined in a Canadian hemodialysis unit. A time-and-motion technique was used to determine the nursing time for preparation and administration. Fixed anemia costs were inventory control, monitoring, blood sampling, and laboratory analysis. Variable costs were those which varied with dosing frequency. The costs are expressed in Canadian dollars (2005).. The mean time associated with preparation and administration was 3.2 min/injection. The annual nonacquisition per patient cost was CAD 2,290.04. Fixed costs were CAD 1,946.01, while the variable costs were CAD 344.03/year. Sensitivity analysis showed a decrease in cost to CAD 1,611.34, if iron monitoring were decreased from monthly to 3 monthly, and to CAD 2,090.66, if patients were converted to less frequent dosing using darbepoetin alfa.. The nonacquisition costs associated with anemia therapy in hemodialysis patients are considerable. Less frequent monitoring of iron therapy and less frequent dosing could decrease costs by CAD 678.40 and CAD 199.38/patient/year, respectively.

Topics: Anemia; Comorbidity; Epoetin Alfa; Erythropoietin; Health Care Costs; Humans; Kidney Failure, Chronic; Models, Economic; Ontario; Recombinant Proteins; Renal Dialysis

Topics: Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Recombinant Proteins; Research Design

Topics: Anemia; Centers for Medicare and Medicaid Services, U.S.; Conflict of Interest; Darbepoetin alfa; Drug Industry; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Medical Oncology; Medicare; Neoplasms; Nephrology; Product Surveillance, Postmarketing; Recombinant Proteins; United States; United States Food and Drug Administration

Topics: Anemia; Cost Allocation; Drug Prescriptions; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Medicare; Recombinant Proteins; Reimbursement Mechanisms; Renal Dialysis; United States

Topics: Anemia; Cost Control; Drug Prescriptions; Drug Utilization; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Medical Audit; Medicare; Nephrology; Outcome Assessment, Health Care; Recombinant Proteins; Reimbursement Mechanisms; United States

Topics: California; Epoetin Alfa; Erythropoietin; Hematocrit; Humans; Kidney Failure, Chronic; Medicare; Recombinant Proteins

Topics: Anemia; Decision Making; Epoetin Alfa; Erythropoietin; Humans; Kidney Failure, Chronic; Patient Participation; Recombinant Proteins; Renal Dialysis

In several studies, hemodialysis (HD) patients treated with recombinant human erythropoietin (rHuEPO) because of renal anemia showed increased levels of soluble adhesion molecules. The purpose of the study was to investigate the changes of soluble P-selectin (sSELP) and its relationship to platelet activation during a single HD session in patients with long-term rHuEPO treatment. Fifty-two HD patients with chronic renal failure were involved--26 with rHuEPO treatment (EPO group) and 26 without (non-EPO group). Thirty healthy subjects served as the control group. The sSELP, beta-thromboglobulin, and platelet factor 4 plasma levels were measured before and after a single 4-hour HD session on a cuprophane dialyzer. The basal beta-thromboglobulin and platelet factor 4 plasma levels were significantly increased in both HD groups compared with healthy controls but did not change after a single HD session, except for a significant decrease of platelet factor 4 in the non-EPO group. The predialysis sSELP plasma levels did not differ significantly compared with those of the healthy controls, but there was a significant increase of sSELP levels after a single HD session in both groups (EPO, P < .005; non-EPO, P < .05, respectively). These results suppose that the increased sSELP level was released from platelets during the course of a single HD session. The more significant increase of the sSELP plasma levels in EPO group during HD indicates that platelets are more activated in patients with long-term rHuEPO treatment, and this fact could partially explain the suspected tendency for thrombosis in these patients.

Topics: Adolescent; Adult; Aged; Anemia; Case-Control Studies; Epoetin Alfa; Erythropoietin; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; P-Selectin; Platelet Activation; Recombinant Proteins; Renal Dialysis; Solubility

Anemia is common in end-stage renal disease (ESRD) patients and an important determinant for left ventricular hypertrophy (LVH) in dialysis patients. There are increasing numbers of biosimilar epoetin-alfa entering Thailand.. To conduct a prospective trial to evaluate the efficacy and safety of a biosimilar epoetin-alfa (epoetin) (Espogen) in ESRD patients receiving chronic hemodialysis complicated by anemia and to address its impact on the left ventricular mass index (LVMI) and volume index (LVVI) in these patients.. Twenty-two hemodialysis (HD) subjects were recruited from Rajavithi and Huachiew Hospitals. Inclusion criteria were chronic HD, hemoglobin (Hb) < 10 g/dL without preceding treatment (epoetin or transfusion) for 1 month. Echocardiographic baselines were obtained Epoetin-alfa was initially given 4,000 IU subcutaneously twice a week and titrated biweekly to keep the Hb range of 11 to 12 g/dL (titration period 12 weeks). Treatment continued until the end of 24 weeks. Records were made for conventional blood tests, blood pressure, amount of drugs needed to control blood pressure, and adverse events. Echocardiogram was repeated (on observer blinding) at the completion of the present study.. After 24-week of epoetin therapy, the predialysis Hb level increased significantly from 8.0 +/- 1.3 g/dL to 11.0 +/- 1.1 g/dL (p < 0.001). The mean dose of epoetin at the present study entry was 143.6 +/- 87.8 IU/kg/ week. At the present study entry, LVH was present in 86.4% of the patients. At the completion of the present study, a decrease in LVMI was observed in 50% of the patients; however, the mean LVMI change was not significantly different. Notably, there were minimal but significant changes in LVEDD (52.8 +/- 7.0 vs. 50.1 +/- 6.9 mm, p < 0.05), LVVI (86.2 +/- 25.2 vs. 75.5 +/- 19.5 mL/m2, p < 0.05) and when subjects were partitioned into tertiles of baseline LVMI, the LVVI change was confined to the highest tertile (103.7 +/- 25.2 vs. 79.6 +/- 21.9 mL/ m2, p < 0.05). The aortic root diameter also significantly decreased despite some increase in blood pressures but without significant change in number of antihypertensive agents. No serious adverse event was observed during the present study period.. The efficacy of anemia treatment and safety of the biosimilar epoetin-alfa was demonstrated in hemodialysis patients. Significant regression of LVVI and some reduction in LVMI were shown in this 24-week prospective trial.

Topics: Adult; Aged; Anemia; Epoetin Alfa; Erythropoietin; Female; Health Status Indicators; Heart Ventricles; Hemoglobins; Humans; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Renal Dialysis; Time Factors; Treatment Outcome; Ultrasonography

The purpose of this initiative was to compare erythropoietin-alpha doses in hemodialysis patients who changed from subcutaneous to intravenous administration. The Manitoba Renal Program switched routes due to concern about erythropoietin-associated pure red cell aplasia.. We compared the erythropoietin-alpha dosage requirements during subcutaneous administration (3 months pre-switch) and intravenous administration (months 4-6 post-switch). We also compared: hemoglobin, transferrin saturation (Tsat%), ferritin, and percent of patients receiving intravenous iron. The same erythropoietin-alpha regimen was initially used when patients were switched.. Of the 628 patients receiving erythropoietin-alpha, the data were complete for 400. The dose increased 26% (mean +/- SD, 10,425 +/- 7,330 vs. 13,125 +/- 8,638 IU/week; p < 0.0001), despite similar hemoglobin, (mean +/- SD, 11.5 +/- 1.1g/dl (114.9 +/- 11.2 g/l) vs. 11.3 +/- 1.0 g/dl (113.5 +/- 10.4 g/l); p = 0.0450) and iron parameters (Tsat 30.9%, ferritin 464 ng/ml (microg/l) vs. Tsat 28.7%, ferritin 538 ng/ml (microg/l)). For the subgroup of 84 patients who maintained target hemoglobin (10-11 g/dl or 110-120 g/l) for both periods, the dose increased 26% (mean +/- SD, 8,393 +/- 6,242 vs. 10,589 +/- 7,049 IU/week; p < 0.0001) without a change in hemoglobin, (mean +/- SD, 11.5 +/- 0.3 g/dl (115.2 +/- 3.0 g/l) vs. 11.5 +/- 0.3 g/dl (114.9 +/- 3.3 g/l); p = 0.5789). When stratified by subcutaneous dose, patients with the lowest dose (<5,000 IU/week) demonstrated the greatest increase (89%), and those with the highest dose (>20,000 IU/week) experienced no increase (-3%).. Overall, erythropoietin-alpha doses increased by 26% when patients were converted from subcutaneous to intravenous administration.

Topics: Anemia; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Injections, Intravenous; Injections, Subcutaneous; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Renal Dialysis

In patients on chronic hemodialysis (CHD), hyperparathyroidism (HPTH) is associated with anemia and resistance to erythropoietin (EPO). In the last few years, calcitriol intravenously (IV) has been used with success in the treatment of the HPTH, secondary to chronic renal failure. However, the effects of calcitriol on the hematological parameters of these patients have never been well evaluated. This study included 11 elderly CHD patients (f = 6, m = 5; mean age = 73.6 years, mean time on CHD = 42.8 months) with HPTH under EPO therapy (IV). They were treated for 12 months with calcitriol IV (mean dose = 2.33 mcg/pt/week). Patients with iron deficiency anemia (ferritin < 200 ng/ml) were excluded. The patients were compared before and after 12 months of calcitriol treatment, with respect to several laboratory parameters and with respect to EPO dose. A paired t-test was used. After treatment, we found a decrease of PTH (634 vs. 418 pg/ml, P = 0.029); the serum calcium increased (8.8 vs. 9.9 mg/dl, P = 0.002); no differences were noted in the plasma levels of alkaline phosphatase, phosphorous, BUN, creatinine, Na and K. Mean levels of Hb (10.2 vs. 11.4 g/dl, P = 0.004) and the Hct (30 vs. 34.3, P = 0.004) increased after 12 months of calcitriol; the levels of serum iron (70 vs. 78 microg/dl, P = ns) and ferritin (531 vs. 785 ng/ml, P = ns) and the EPO dose (105 vs. 100 U/kg/week, P = ns) were similar before and after treatment. Our data show that the treatment of HPTH in CHD elderly patients with calcitriol can increase Hb level without increasing EPO dose.

Topics: Aged; Calcitriol; Calcium Channel Agonists; Epoetin Alfa; Erythropoietin; Female; Follow-Up Studies; Hematinics; Hemoglobins; Humans; Hyperparathyroidism, Secondary; Infusions, Intravenous; Kidney Failure, Chronic; Male; Recombinant Proteins; Renal Dialysis

The erythropoietic-stimulating hormone, darbepoetin alfa (Aranesp; DPO; Amgen, Thousand Oaks, California) is a long-acting agent growing in popularity as the preferred anemia management agent for patients with chronic kidney disease. Use of this drug in existing patients treated with rHu-EPO (epoetin alfa; EPO) requires conversion dosing and the potential for serious alterations in previously stable and satisfactory hemoglobin levels. This study analyzed the dosing conversion recommended by Amgen to determine if the regimen resulted in stable hemoglobin values during the conversion.. Twenty-nine stable patients on hemodialysis were selected for conversion from EPO to DPO. The dose of DPO was taken from the conversion table recommended by Amgen and based upon the patient's weekly EPO dose. The mean conversion dose was 40 mcg weekly. The patients were monitored monthly with hemoglobin, hematocrit routine chemistries, and iPTH levels according to unit policy. The dose of DPO was individually titrated to maintain the hemoglobin concentrations at target levels between 11.5 gm/dL and 13.3 gm/dL. At the end of six months, there was an analysis of the data to determine if the results warranted an adjustment in the DPO dose and if so, what the adjusted dosing factor should be.. Fifty-seven percent of the patients in the study group experienced a drop in hemoglobin levels below pre-DPO baseline levels (13.1 +/- 0.6 gm/dL) by the third month. The mean hemoglobin level dropped to 11.0 +/- 1.2 gm/dL for the entire group, representing a mean 2 +/- 1.42 gm/dL reduction. Forty-five percent of patients had a 15% to 40% drop in hemoglobin (1.9 gm/dL-5.0gm/dL). By the sixth month, patients were back to baseline hemoglobin (13.2 +/- 2.0 gm/dL). The adjusted dose at this point averaged 107 mcg weekly. Statistical analysis suggested an adjustment of 48.4 mcg to each of the Amgen recommended dose conversion values.. The current Amgen recommended DPO dose regimen for conversion from EPO resulted in a drop in hemoglobin from baseline levels in 57.2% of patients, suggesting that the current conversion table may underestimate the dose. Based upon a statistical analysis, an additional 48.4 (50) mcg to each recommended dose is needed to maintain baseline levels.

Topics: Algorithms; Anemia; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins

Fistula thrombosis in patients on maintenance hemodialysis is an important morbidity factor. Arterial or venous thrombotic events have been described as complications in patients on regular hemodialysis. This study was designed to evaluate the risk factors for arteriovenous fistula thrombosis.. One hundred and seventy-one patients with arteriovenous fistula on maintenance hemodialysis were studied prospectively during a period of 14 months for any episode of arteriovenous fistula thrombosis, after anticardiolipin antibodies were assayed by ELISA. Other risk factors for thrombosis such as the presence of diabetes or hypertension, the use of erythropoietin (rhEPO), fistula site, gender, age, ultrafiltration, hypotension during dialysis, and the number of dialysis visits in a week were assessed.. Fifty-six percent of patients had IgG-anticardiolipin antibodies > or = 10GPL, which was significantly correlated with dialysis duration (23.18 +/- 24.56 months in patients with anticardiolipin antibodies < or = 10GPL vs. 37.73 +/- 36.35 months in patients with 20 < or = IgG-anticardiolipin antibodies < 40GPL). Within the 14 months of follow-up, 36 episodes of arteriovenous fistula thrombosis occurred in 31 patients (18.1%). Considering anticardiolipin antibodies and other risk factors in a Cox proportional hazard model, only fistula site (P = 0.021, RR = 2.48, Cl = 1.14 - 5.37) and erythropoietin (Eprex) use (P = 0.021, RR = 10.92, Cl = 1.43 - 83.02) seemed to have an influence on fistula patency. According to fistula site, the survival of brachiocephalic fistulas were significantly (P = 0.007) better than radiocephalic ones (1- and 3-year survival were 95% and 87% for upper, and 88% and 72% for lower ones, respectively).. Although the incidence of the anticardiolipin antibody was high in our patients, in the presence of other risk factors for thrombosis, we found no correlation between IgG-anticardiolipin antibodies and arteriovenous fistula thrombosis. Instead, erythropoietin (Eprex) use and fistula site seem to have an important role in the correlation between IgG-anticardiolipin antibodies and arteriovenous fistula thrombosis.

Topics: Antibodies, Anticardiolipin; Arteriovenous Shunt, Surgical; Catheters, Indwelling; Epoetin Alfa; Erythropoietin; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Proportional Hazards Models; Prospective Studies; Recombinant Proteins; Renal Dialysis; Risk Factors; Survival Analysis; Thrombosis

Topics: Anemia; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Hematocrit; Humans; Kidney Failure, Chronic; Recombinant Proteins; Renal Dialysis; Survival Analysis

Few observational studies have evaluated the use of epoetin alfa (EPO) and darbepoetin alfa (DARB) in chronic kidney disease (CKD) patients with anemia. The objective of this study was to investigate dosing patterns, hematologic outcomes, and intervention costs with EPO and DARB in anemic CKD patients treated in an ambulatory care setting.. This was a multicenter, retrospective, chart review of predialysis CKD patients with anemia treated with EPO or DARB. Charts were sequentially selected from 435 EPO and 432 DARB patients naive to erythropoietic therapy and treated for > or = 24 weeks. Hemoglobin (Hb) levels, dates, and EPO/DARB doses were recorded. Drug costs using 2005 wholesale acquisition costs (WAC) and Federal Supply Schedule (FSS) pricing were based on the mean cumulative drug dose over the 24-week study period.. A total of 393 EPO and 396 DARB charts met all criteria with predominantly male subjects (EPO: 94%; DARB: 96%). Mean baseline GFR and Hb levels were similar. Once-weekly and extended dosing (> or = Q2W) was common in both groups. At Weeks 4, 8, and 12 following initiation of therapy, a greater proportion of EPO than DARB patients reached target Hb levels (> or = 11 g/dL) (p < 0.0001); at Week 24, all patients reached target Hb levels. Mean 24-week cumulative doses were EPO 279 336 +/- 68 302 units and DARB 1084 +/- 246 microg. Drug cost was higher for DARB independent of pricing utilized (WAC: EPO = 3400 US dollars, DARB = 4726 US dollars; FSS: EPO = 1528 US dollars, DARB = 2379 US dollars).. Extended dosing (Q2W) was common in EPO- and DARB-treated patients with CKD-related anemia, with EPO-treated patients experiencing a significantly greater hematologic response (at Weeks 4, 8, and 12). In addition, drug cost was 39-56% higher in the DARB group. The male predominance may limit generalizability, warranting further research in other populations.

Topics: Anemia, Hemolytic; Darbepoetin alfa; Disease Progression; Dose-Response Relationship, Drug; Drug Costs; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Retrospective Studies; Time Factors; Treatment Outcome

To determine if temporary discontinuation of epoetin therapy in anemic patients with end stage renal disease (ESRD) influences their responsiveness to epoetin.. We performed a post hoc analysis of the data from two consecutive single-center randomized trials (T1 and T2) comparing the efficacy of two epoetin products (E1 and E2) in anemic patients with ESRD. The analysis included a subset of 44 patients who participated in both trials and were not receiving epoetin in the period (median, 12 months; range 5-15) between the trials due to epoetin shortage. Two co-primary outcomes were average weekly hemoglobin difference from the baseline and average weekly epoetin dose.. With adjustment for potential differences between E1 and E2, average weekly hemoglobin difference of 1.21 g/dL from the baseline was lower in T2 than that of 1.71 g/dL in T1: difference -0.49 (95% confidence interval [CI], -0.68 to -0.29; P<0.001). Average weekly epoetin dose of 107 IU/kg in T2 was higher than 96 IU/kg in T1 (ratio, 1.13; 95% CI, 1.04-1.24; P=0.009). With additional adjustment for within-subject changes in baseline covariates from T1 to T2 (baseline hemoglobin, body mass index, serum albumin, ferritin and transferrin saturation, intact parathormone, C-reactive protein, dialysis dose, and use of angiotensin converting enzyme inhibitors), hemoglobin response remained lower (adjusted difference, -0.44 g/dL; 95% CI, -0.73 to -0.16; P=0.004) and weekly epoetin dose remained higher in T2 than inT1 (adjusted ratio, 1.17; 95% CI, 1.03-1.34; P=0.016).. In patients with ESRD, responsiveness to epoetin was lower in T2 after a period of epoetin therapy discontinuation than in T1 epoetin trial. Since this could not be explained by within-subject changes in factors known to affect response to epoetin, a prolonged withdrawal of epoetin in patients with ESRD might independently contribute to a reduced responsiveness to epoetin at a later re-exposure.. ClinicalTrials.gov Identifier for T1 trial: NCT00322413.

Topics: Anemia; Epoetin Alfa; Erythropoietin; Hemoglobins; Humans; Kidney Failure, Chronic; Middle Aged; Randomized Controlled Trials as Topic; Recombinant Proteins; Renal Dialysis; Treatment Outcome

Topics: Adverse Drug Reaction Reporting Systems; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Recombinant Proteins; Red-Cell Aplasia, Pure; Risk Assessment; Risk Factors

Epoetin alfa (EPO) and darbepoetin alfa (DARB) are erythropoietic agents indicated in the United States for the treatment of anemia in chronic kidney disease (CKD).. This study investigated dosing patterns and costs associated with the use of erythropoietic-stimulating therapy (EST) in patients with CKD not on dialysis who were newly starting EPO or DARB therapy in managed care organizations.. This was a retrospective analysis of medical claims data from >30 health plans for the period from July 2002 to February 2005. Patients were included if they were aged > or =18 years, had > or =1 claim for CKD within 90 days before the initiation of treatment, had newly started therapy with EPO or DARB, and had received > or =2 doses of treatment. If a patient was undergoing renal dialysis, data were censored 30 days before the first date of dialysis. Patients with a diagnosis of cancer or who had undergone chemotherapy were excluded from the analysis. The mean dosing interval was determined for both groups. Mean weekly doses and costs (using 2005 wholesale acquisition costs), weighted by the treatment duration, were calculated. The frequency of outpatient nephrologist visits was described and included in cost considerations.. The study population consisted of 595 patients who received EPO and 260 who received DARB. The EPO group was significantly older than the DARB group (mean age, 63.5 vs 61.2 years, respectively; P = 0.020). The proportion of women was similar between the 2 groups (51.6% and 50.4%). Use of extended dosing (> or =q2wk) was common in both groups (63.2% and 90.8%). The weighted mean weekly dose was 11,536 U for EPO and 42.5 mug for DARB. The mean number of outpatient nephrologist visits during treatment was similar between the 2 groups (3.9 and 3.5). Mean weekly costs (EST drug cost plus cost of nephrologist visits) were significantly lower for EPO compared with DARB (159 dollars vs 205 dollars; P < 0.001).. The majority of these CKD patients newly started on EST in managed care organizations received extended dosing regimens (> or =q2wk) of EPO or DARB. EPO treatment was associated with significantly lower mean weekly costs compared with DARB. The number of outpatient nephrology visits did not differ significantly between groups.

Topics: Anemia; Darbepoetin alfa; Dose-Response Relationship, Drug; Drug Costs; Epoetin Alfa; Erythropoietin; Female; Follow-Up Studies; Health Maintenance Organizations; Hematinics; Humans; Kidney Failure, Chronic; Male; Middle Aged; Office Visits; Outpatients; Recombinant Proteins; Renal Dialysis; Retrospective Studies; Treatment Outcome

To investigate dosing patterns and drug costs of erythropoietic agents and assess the frequency of outpatient nephrologist visits in an elderly population with pre-dialysis chronic kidney disease (pCKD) newly initiated on epoetin alfa (EPO) or darbepoetin alfa (DARB).. An analysis of medical claims from more than 30 healthcare plans covering all census regions of the US in the period July 2002 through February 2005 was conducted. Patients were included if they were > or = 65 years of age, had at least one claim for CKD within 90 days prior to the initiation of any erythropoietic agent, were newly commenced on either EPO or DARB, and had received at least two treatment doses. If a patient received renal dialysis, data were censored 30 days prior to the first date of dialysis. Patients diagnosed with cancer or those who had undergone chemotherapy were excluded from the analysis. The average dosing interval for both EPO and DARB was calculated and classified as once weekly (qw), every 2 weeks (q2w) or every 3 weeks or less frequently (> or = q3w). Weighted average weekly doses were scaled based on treatment duration. The frequency of outpatient nephrologist visits was analysed. Average weekly treatment costs were calculated and presented using the May 2005 Wholesale Acquisition Costs.. A total of 293 EPO and 102 DARB patients met the inclusion criteria. The two groups of patients had similar mean age (74.4 years for EPO vs 74.3 years for DARB) and gender distribution (47.4% female for EPO vs 51.0% for DARB). Extended dosing (every 2 weeks or less frequently: > or = q2w) during treatment was observed in both groups (EPO: qw 49.8%, q2w 31.7%, > or = q3w 18.4%; DARB: qw 19.6%, q2w 52.9%, > or = q3w 27.5%). The average dosing interval between injections was 13.6 days for the EPO group and 17.3 days for the DARB group. The weighted average weekly dose was 12,748 units for EPO and 43.5 microg for DARB. The average weekly erythropoietic treatment cost was significantly greater for DARB compared with EPO (190 US dollars vs 155 US dollars per week [2005 values]; p = 0.028). After controlling for covariates, the cost difference between the two groups was more pronounced and remained statistically significant (adjusted cost difference 41 US dollars/week higher for DARB patients; p = 0.013). The frequency of outpatient nephrologist visits during treatment was similar between the two groups (EPO 3.4 vs DARB 3.0 visits).. Based on this analysis of claims data from more than 30 US healthcare plans, extended dosing (> or = q2w) of EPO and DARB was common in elderly pCKD patients treated with erythropoietic agents, with significantly higher weekly drug costs observed in the DARB group compared with the EPO group. The number of outpatient nephrologist visits was not significantly different between EPO and DARB patients. This study was the first to evaluate the dosing patterns of EPO and DARB in elderly pCKD patients in a large managed care population.

Topics: Aged; Anemia; Cohort Studies; Darbepoetin alfa; Dose-Response Relationship, Drug; Drug Costs; Epoetin Alfa; Erythropoietin; Health Care Costs; Humans; Kidney Failure, Chronic; Managed Care Programs; Office Visits; Recombinant Proteins; Renal Dialysis; Retrospective Studies

Topics: Drug Approval; Epoetin Alfa; Erythropoietin; Evidence-Based Medicine; Hematinics; Humans; Kidney Failure, Chronic; Nephrology; Practice Guidelines as Topic; Recombinant Proteins; Research Design; Total Quality Management; United States; United States Food and Drug Administration

Topics: Anemia; Cardiovascular Diseases; Drug Industry; Epoetin Alfa; Erythropoietin; Hemoglobins; Humans; Kidney Failure, Chronic; Recombinant Proteins; Renal Dialysis

Erythropoiesis stimulating agents (ESAs) represent a significant cost for health care establishments, which are now subjected to new restrictions on how these agents can be dispensed, as laid down in the Decree of 24th August 2005 relating to a contract for the proper use of drugs, medical products and services. To optimize the treatment plan, ensure that these agents are used properly and satisfy the new requirements, a multidisciplinary expert group has drawn up a guide for health professionals which presents: important points specifically addressing the modalities of administration of ESAs in patients with renal disease treated by hemodialysis; a risk assessment which has helped identify preventive measures; proposals for preventive or corrective actions against medication risks or errors; an internal frame of reference for use in drawing up protocols and evaluating practices. This guide should promote a better use of ESAs once it is adopted by health care establishments, who must adapt it to their internal operations and provide suitable informational education. Training the relevant players in how to assess professional practices, together with the work of the multidisciplinary study group, are key factors that should help make this initiative a success.

Topics: Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Practice Guidelines as Topic; Recombinant Proteins; Renal Dialysis

Despite an increase in the use and average dose of recombinant human EPO (rh-EPO) over the last 15 years, a substantial percentage of patients still do not achieve hemoglobin targets recommended by international guidelines. The definition of rh-EPO resistance has been introduced to identify those patients in whom the target hemoglobin level is not attained despite a greater-than-usual dose of erythropoietin-stimulating agent (ESA). In recent years, increasing attention has been paid to the relationship between dialysis, increased inflammatory stimulus, malnutrition, and ESA response. About 35% to 65% of hemodialysis patients show signs of inflammation that could be a cause of anemia through the suppression of bone marrow erythropoiesis by a number of cytokines. A large proportion of chronic kidney disease patients also have protein-energy malnutrition and wasting; low serum albumin levels, together with other more specific nutritional markers, are predictors of rh-EPO response. A diminished nutritional state could then be a feature of patients who are resistant to ESA treatment, with malnutrition probably being a consequence of a chronic inflammatory state. Starting from the hypothesis that anemia, partially attributable to a reduced response to ESA, could be the link among malnutrition, inflammation, and the poor outcome of chronic kidney disease patients, we designed a multicenter observational study, the Malnutrition-Inflammation-Resistance-Treatment Outcome Study (MIRTOS), aimed at evaluating the impact and possible causes of resistance to ESA in a large sample of hemodialysis patients. We hope the results of MIRTOS will represent a step forward toward a better understanding of the factors influencing the response to ESA in hemodialysis patients.

Topics: Anemia; Chronic Disease; Darbepoetin alfa; Drug Resistance; Epoetin Alfa; Erythropoietin; Hemoglobins; Humans; Inflammation; Kidney Diseases; Kidney Failure, Chronic; Malnutrition; Protein-Energy Malnutrition; Recombinant Proteins; Renal Dialysis

There are conflicting reports about the importance of the renin-angiotensin system (RAS) on erythropoietin (Epo) sensitivity in haemodialysis patients, but the role of gender has not been studied specifically. The hypothesis underlying this study is that Epo resistance associated with RAS blockade (RASB) is specific to men and related to drug-induced lowering of circulating testosterone.. Men and women undergoing chronic haemodialysis were divided into groups according to whether or not they were receiving RASB. Serum was collected pre-dialysis for determination of free testosterone levels by enzyme immunoassay. Routine laboratory data and Epo doses were collated and analysed for the 3 month period prior to the measurement of the hormone level.. Control women required more Epo than control men (P=0.002), but the Epo doses between men and women with RASB were similar. Men with RASB required more Epo than control men (P=0.002), but RASB had no effect on Epo requirements in women. There was a significant relationship between age and testosterone levels in control men (P=0.01) that was not present in men taking RASB. RASB was associated with lower levels of serum testosterone in men <60 years old (P=0.02), but had no effect on serum testosterone levels in older men or women. Multiple regression analysis demonstrated that serum testosterone negatively correlated with Epo dose (P=0.045) when all groups of patients were considered together.. These data suggest that androgens may participate in Epo resistance associated with RASB in patients on haemodialysis, and that the effect is related to both gender and age.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Case-Control Studies; Drug Resistance; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Sex Factors; Testosterone

Anemia is adversely associated with poor uremia control and is an established cardiovascular risk factor in patients with end-stage renal disease (ESRD). Nocturnal home hemodialysis (NHD) is a novel form of renal replacement therapy that offers superior clearance of uremic solutes and improvements in several cardiovascular outcome parameters. We conducted a retrospective cohort study to test the hypotheses that augmenting the dose and frequency of dialysis by NHD would improve hemoglobin (Hb) concentrations and decrease requirement of erythropoietin (EPO) in ESRD patients.. In 63 patients (mean age: 46 +/- 2 years) receiving NHD (mean duration: 2.1 +/- 0.2 years), Hb, EPO dose, iron saturation, ferritin were determined before and at six monthly repeated intervals after conversion to NHD. For comparison, 32 ESRD patients (mean age: 57 +/- 3 years) who remained on self-care conventional hemodialysis (CHD) were also studied.. There were no differences in baseline Hb concentrations, iron saturation, ferritin, or EPO dose between the two cohorts. After transfer from CHD to NHD, there were significant improvements in Hb concentrations (from 115 +/- 2 to 122 +/- 3 (6 months) and 124 +/- 2 (12 months) g/l, p = 0.03) despite a fall in EPO requirement (from 10,400 +/- 1400 to 8500 +/- 1300 (6 months) and 7600 +/- 1100 (12 months) U/week, p = 0.03). In contrast, CHD cohort had no change in EPO requirement (from 8300 +/- 1100 to 8100 +/- 1300 (6 months) and 8600 +/- 1000 (12 months) U/week, p > 0.05) or Hb concentrations (from 110 +/- 2 to 115 +/- 3 (6 months) and 115 +/- 2 (12 months), p > 0.05). There was a higher percentage of ESRD patients who did not require EPO in the NHD cohort (24% vs. 9.4%, p = 0.01). Lower Hb concentrations were noted in the CHD cohort despite higher iron saturation (0.25 +/- 0.01 (NHD) vs. 0.33 +/- 0.02 (CHD), p = 0.02) at the end of follow-up.. Enhancing uremic clearance by NHD resulted in a rise in Hb and a fall in EPO requirement.

Topics: Adult; Anemia; Cohort Studies; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemodialysis, Home; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Retrospective Studies

The European Survey of Anaemia Management 2003 (ESAM 2003) was a 1 day randomized survey conducted to assess anaemia management in dialysis patients 4 years after the introduction of the European Best Practice Guidelines. The survey included 8100 patients from 11 European countries and Israel. Overall, haemoglobin (Hb) levels > or =11.0 g/dl, as recommended by the guidelines, were achieved in 66% of patients. Only 48% of patients had adequate iron status, with transferrin saturation values missing for 27% and functional or absolute iron deficiency reported for 17 and 9%, respectively. In order to identify factors affecting epoetin dose and Hb levels, the countries were divided into two groups based on the percentage of patients with Hb levels > or =11.0 g/dl (>70% in group 1 and 60-70% in group 2). The most probable causes for better management in group 1 were administration of higher epoetin doses and better monitoring and management of iron status. In patients with Hb <11.0 g/dl, mean epoetin-alpha/beta doses were significantly lower for subcutaneous than intravenous (i.v.) administration, whereas mean doses were similar for both routes in patients with Hb > or =11.0 g/dl. When standardized for Hb levels, the dose ratio of i.v. epoetin-alpha/beta to i.v. darbepoetin alfa was 176:1 (95% confidence interval, 166:1-189:1). Limited comparisons between the eight countries that participated in ESAM 2003 and the original ESAM revealed that many patients still have haemoglobin levels below the current recommendations despite significant improvements in management of renal anaemia over the last 5 years.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Epoetin Alfa; Erythropoietin; Europe; Female; Health Surveys; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Retrospective Studies

Current guidelines give evidence-based advice on how best to manage anaemia in patients with renal disease, but these guidelines do not consider individual patient needs, so tailoring anaemia management to each patient still remains a challenge for the treating physician. Two case studies are described that illustrate some of the key factors that need to be considered. The first case emphasizes that haemoglobin (Hb) targets recommended in current guidelines may not suit all patients. The patient had been stably maintained on subcutaneous epoetin therapy with an average Hb concentration of >13.0 g/dl because he developed angina symptoms when his Hb level fell to 12.2 g/dl. Iron deficiency was identified as the likely cause of falling Hb in this patient. After the patient's iron supplementation was increased, his Hb level was normalized back to >13.0 g/dl without increasing the epoetin dose, and the angina symptoms were resolved. The second case involved a pre-dialysis patient with diabetes, who required a higher dose of epoetin after beginning concomitant antihypertensive treatment with an angiotensin-converting enzyme inhibitor. Previously, the treatment of renal anaemia in pre-dialysis patients has not been the focus of attention. Two ongoing randomized controlled trials have been designed to study early initiation of epoetin treatment in pre-dialysis patients and will provide much needed information in this area.

Topics: Aged; Anemia; Angiotensin-Converting Enzyme Inhibitors; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Hypertension; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis

The total number of end-stage renal disease patients treated by renal replacement therapy increased from 1584 on 31 December 2002 to 1661 on 31 December 2003 (4.9% increase). Of these patients, 70.5% were treated by hemodialysis, 7.0% by peritoneal dialysis and 22.5% had a functioning renal graft. The patients were treated at 18 dialysis centers and one transplant center. The number of prevalent patients treated by renal replacement therapy per million of the population (p.m.p.) was 846 at the end of 2003. The number of incident (new) patients in 2003 was 131 p.m.p. The gross mortality rate of dialysis patients was stable through the years of the study and reached 11.8% in 2003. 57.6% of new patients starting hemodialysis were > or = 65 years old and 23.2% were diabetics. Epoetin therapy was prescribed to 89.8% of dialysis patients. The number of patients positive for hepatitis B or hepatitis C viruses is stable and low (3.1% of all dialysis patients).

Topics: Age Factors; Aged; Diabetes Complications; Epoetin Alfa; Erythropoietin; Hematinics; Hepatitis B; Hepatitis C; Humans; Incidence; Kidney Failure, Chronic; Kidney Transplantation; Peritoneal Dialysis; Prevalence; Recombinant Proteins; Renal Dialysis; Renal Replacement Therapy; Slovenia

The effectiveness of extended dosing of epoetin alfa beyond once-weekly (QW) has not been well explored in patients being treated for anaemia of chronic kidney disease (CKD). The current study was undertaken to assess the effectiveness of extended dosing in maintaining haemoglobin (Hb) levels in this population.. A retrospective chart review was conducted to assess the efficacy of extended epoetin alfa dosing in patients being treated for CKD-related anaemia. Eligible patients were to have received epoetin alfa once every 2 weeks (Q2W), 3 weeks (Q3W), 4 weeks (Q4W), or >Q4W administered subcutaneously for at least 3 months to maintain Hb > or = 11.0 g/dl. Patients were > or =18 years with serum creatinine 1.5 to 6.0 mg/dl for females and 2.0 to 6.0 mg/dl for males, and were not receiving renal replacement therapy. Epoetin alfa dose and dosing frequency were adjusted during treatment at the clinician's discretion. For analysis, patients were stratified into dosing groups based on their most dominant dosing regimen.. 243 patients (mean age, 71.5 years; 79% white, 54% female) who received extended epoetin alfa dosing for a mean of 10.3 months were eligible for analysis. Mean baseline estimated glomerular filtration rate and mean serum creatinine were 21.2 ml/min/1.73 m(2) and 3.1 mg/dl, respectively. Primary causes of CKD included hypertension (36%) and diabetes (28%). Most patients (82%) receiving an extended epoetin alfa regimen maintained Hb > or =11.0 g/dl. The most common dosing regimen was Q2W (51%). Mean Hb for each dosing group was maintained between 11.6 g/dl and 12.4 g/dl during the study, and glomerular filtration rate remained stable. Epoetin alfa was well tolerated across all groups.. Data from private community nephrology practices showed that extended epoetin alfa dosing effectively maintained Hb > or =11.0 g/dl in 82% of these selected patients being treated for anaemia of CKD.

Topics: Aged; Anemia; Blood Transfusion; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Glomerular Filtration Rate; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Recombinant Proteins; Retrospective Studies; Safety

In 2002, many haemodialysis patients were switched from subcutaneous (s.c.) to intravenous (i.v.) administration of epoetin-alpha following reports of antibody formation and development of pure red-cell aplasia in patients treated via the s.c. route. We evaluated the possible effect of this change in the route of administration on haemoglobin (Hb) levels and epoetin-alpha requirements.. This retrospective survey involved 223 haemodialysis patients from 25 Swedish centres. Variables were recorded before and after a mean period of 213 days (range 89-297 days) after the change in the route of administration.. The mean epoetin-alpha do had to be increased from 159+/-104 to 185+/-122 U/kg/week (p<0.0001) to maintain a constant Hb level (121+/-12 vs 120+/-11 g/l). Plasma ferritin, albumin, C-reactive protein, iron, iron transferrin saturation and body mass index remained constant. The relative increase in epoetin-alpha dose was negatively correlated with the s.c. dose prior to the switch (R=-0.3; p<0.0001), with the most pronounced dose increases occurring in patients who received a low s.c. dose.. A switch from s.c. to i.v. administration of epoetin-alpha in haemodialysis patients was accompanied by an increase in the mean dose requirement of 15%. This increase may be less pronounced in patients receiving high s.c. doses prior to the switch.

Topics: Aged; Aged, 80 and over; Anemia; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Injections, Intravenous; Injections, Subcutaneous; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Retrospective Studies; Treatment Outcome

It is unknown to what degree physicians adjust erythropoietin doses to achieve hemoglobin levels (11.0 to 12.0 g/dL [110 to 120 g/L]) recommended by the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (NKF-K/DOQI) for patients with end-stage renal disease receiving hemodialysis. Our objective is to examine epoetin alfa prescribing patterns for achieving the target hemoglobin level range in this population.. Monthly hemoglobin levels and epoetin alfa doses from 2 large databases were retrospectively analyzed. One data set comprised 31,267 patients from the Fresenius Medical Care-North America (FMC-NA) database, and the other comprised 128,761 patients based on claims for Medicare services.. Longitudinal evaluation of the FMC-NA data set showed that hemoglobin levels in patients administered epoetin alfa cycled in and out of the NKF-K/DOQI hemoglobin target range, and doses were decreased in 98.8% of patients with persistent hemoglobin levels greater than 12.0 g/dL (> 120 g/L). Hemoglobin levels in patients from the Medicare data set that initially were outside the target range migrated into the range with epoetin alfa dose titration. FMC-NA patients with a 3-month average hemoglobin level less than 11.0 g/dL (< 110 g/L) were administered significantly greater epoetin alfa doses than those with average hemoglobin levels greater than 12.0 g/dL (> 120 g/L; 21,838 versus 13,503 U/wk; P < 0.0001). Less than 0.4% of patients administered epoetin alfa were persistently anemic (hemoglobin < 11.0 g/dL [< 110 g/L]) and were administered persistently high doses (> 30,000 U/wk), but failed to respond with a 0.5-g/dL or greater (> or = 5-g/L) increase in hemoglobin levels.. In these analyses, few hemodialysis patients experienced persistent anemia while being administered high epoetin alfa doses. Physicians appeared to appropriately adjust doses to achieve hemoglobin levels recommended by the NKF-K/DOQI guidelines.

Topics: Anemia; Cross-Sectional Studies; Databases, Factual; Dose-Response Relationship, Drug; Drug Prescriptions; Drug Utilization; Epoetin Alfa; Erythropoietin; Guideline Adherence; Hemoglobins; Humans; Kidney Failure, Chronic; Practice Guidelines as Topic; Practice Patterns, Physicians'; Recombinant Proteins; Retrospective Studies; Treatment Outcome; United States

Topics: Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Recombinant Proteins; Renal Dialysis

In 1997, the Health Care Financing Administration Hematocrit Measurement Audit (HMA) program initiated use of a 3-month rolling average hematocrit (Hct) level for reimbursement of epoetin claims in hemodialysis patients, with denial of payment when this value exceeded 36.5%. This study evaluated the impact of the HMA program on anemia-related outcomes in hemodialysis patients. An observational, retrospective study of 987 hemodialysis patients from 11 dialysis centers in the United States was performed, collecting data between October 1996 and December 1997. Centers were selected from a pool of nearly all facilities in the United States, which during May 1997 satisfied one of two criteria: greater than 75% of patients at the facility had mean Hct level of > or =33% (Group A) or fewer than 50% of patients at the facility had mean Hct level of > or =33% (Group B). Each facility maintained its own anemia management practices without specific anemia management interventions as part of this study. Hct level, hemoglobin (Hb) level, and epoetin dose were analyzed to compare the pre-HMA period (October 1996 to May 1997) to the HMA period (June to December 1997) and/or for each of the five quarters of the study period. The primary study endpoint was the percentage of patients with Hct levels of > or =33% during each study quarter. The mean Hct level at baseline was 34% in Group A and 33.4% in Group B (p = 0.01). Hct levels, which were increasing before implementation of the HMA program, decreased during the HMA period (p < 0.001 and p = 0.013 in Groups A and B, respectively). The percentage of patients in Groups A and B with mean quarterly Hct levels of > or =33% decreased during the last quarter of the HMA implementation period compared to the quarter immediately preceding the start of the HMA program (p < 0.001 for both comparisons). Changes in Hb levels were similar to those seen in Hct levels. The mean epoetin dose administered decreased from 13,090 U/week at the start of the study to 11,884 U/week immediately before the HMA program took effect (p < 0.05). The HMA program adversely affected anemia treatment outcomes, regardless of whether dialysis units before HMA implementation had <50% of patients with a Hct level of > or =33% or had >75% of patients with a Hct level of > or =33%. The decline in mean weekly dose of epoetin was likely a result of withholding doses out of concern among providers about risk of reimbursement denial.

Topics: Adult; Aged; Anemia; Epoetin Alfa; Erythropoietin; Female; Health Policy; Hematocrit; Humans; Insurance, Health, Reimbursement; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis

Oxidative stress often occurs in chronic hemodialysis (HD) patients. The objective of our study was to investigate the interrelationship between oxidative stress and the degree of renal anemia.. In 107 consecutive HD patients, serum concentrations of two major aldehydic lipid peroxidation (LPO) products, 4-hydroxynonenal (HNE) and malondialdehyde (MDA), and of protein carbonyls were analyzed as parameters of oxidative stress and related to the degree of renal anemia. Additionally, in 76 patients treated with epoetin long-term changes in the serum levels of aldehydic LPO products were observed.. In HD patients, serum levels of HNE, MDA, and protein carbonyls are increased in comparison to controls. The lower the hemoglobin, i.e. the stronger the degree of renal anemia, the higher the serum concentrations of HNE, MDA, and protein carbonyls. The HNE and MDA levels decreased during HD. Long-term studies on the correction of renal anemia by epoetin demonstrated a mitigation of oxidative stress during this therapy. During periods of 1 and 2 years, it was observed that the serum levels of HNE and MDA could be reduced.. Chronic renal failure is connected with oxidative stress which correlates with the degree of renal anemia, and the serum levels of aldehydic LPO products could be reduced during correction of renal anemia by epoetin.

Topics: Aged; Aldehydes; Anemia; Blood Proteins; Chromatography, High Pressure Liquid; Enzyme-Linked Immunosorbent Assay; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Malondialdehyde; Middle Aged; Oxidative Stress; Recombinant Proteins; Renal Dialysis

There have been several recent reports of pure red-cell aplasia (PRCA) mediated by anti-erythropoietin antibodies (AEA) in patients with chronic renal failure treated with recombinant human erythropoietin (EPO). Among the factors thought to trigger this mechanism is the subcutaneous administration of EPO. Despite this being the normal route of administration in patients undergoing peritoneal dialysis (PD), to date there has only been 1 described case of PRCA due to AEA in PD. Herein, we report such a case involving a patient in whom a diagnosis of anemia due to PRCA was particularly difficult to make because of concomitant rectal bleeding.

Topics: Antibodies; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Male; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Recombinant Proteins; Red-Cell Aplasia, Pure

Topics: Adult; Cardiovascular Diseases; Decision Making; Disease Progression; Epoetin Alfa; Erythropoietin; Female; Glomerulosclerosis, Focal Segmental; Hematinics; Humans; Kidney Failure, Chronic; Kidney Transplantation; Morbidity; Neoplasms; Pregnancy; Pregnancy Complications; Recombinant Proteins; Renal Dialysis; Renal Replacement Therapy; Risk Assessment; Uremia

Topics: Anemia; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Humans; Kidney Failure, Chronic; Peritoneal Dialysis, Continuous Ambulatory; Recombinant Proteins

Epoetin alfa (Eprex*; Johnson & Johnson, Manati, PR) has been used successfully to correct the anemia of chronic renal failure for more than 12 years. Anti-erythropoietin (anti-EPO) antibodies have been reported in a small number of patients, resulting in a blood disorder, pure red cell aplasia (PRCA). To evaluate the utility of a large-scale anti-EPO antibody screening program in patients with chronic kidney disease (CKD) administered epoetin alfa, a study involving 5 large renal centers in southern Ontario, Canada, was conducted.. More than 1,500 hemodialysis, peritoneal dialysis, and predialysis patients were screened for the prevalence of anti-EPO antibodies by means of a radioimmunoprecipitation (RIP) assay. Serum samples were drawn and shipped to PPD Development (Richmond, VA) for the immunoprecipitation assay. Serum EPO levels also were measured. All samples that tested positive or borderline for antibodies were sent to MDS Pharma Services (Montreal, Canada) for the neutralization assay.. Of 1,531 samples tested, 1 patient tested low-positive and 3 borderline results were detected by means of RIP. PRCA previously was diagnosed in the patient with the low-positive antibody level; the patient was treated with cyclosporine and currently is being administered epoetin alfa with good response. The 3 patients with borderline antibody results manifested no clinical signs of PRCA. Neutralization assays performed on all 4 serum samples were negative for anti-EPO antibodies.. Results from this surveillance study show that the prevalence of antibody to EPO in patients with CKD administered epoetin alfa in 5 Canadian renal centers is low, and the value of a large-scale antibody screening program for PRCA cannot be justified.

Topics: Aged; Aged, 80 and over; Anemia; Autoantibodies; Autoimmune Diseases; Cross-Sectional Studies; Cyclosporine; Epoetin Alfa; Erythropoietin; Female; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Male; Mass Screening; Middle Aged; Ontario; Peritoneal Dialysis; Population Surveillance; Radioimmunoprecipitation Assay; Recombinant Proteins; Red-Cell Aplasia, Pure; Renal Dialysis

Topics: Centers for Medicare and Medicaid Services, U.S.; Epoetin Alfa; Erythropoietin; Humans; Kidney Failure, Chronic; Practice Guidelines as Topic; Recombinant Proteins; United States

Recombinant Human Erythropoietin (EPO) is extensively used for anemia in renal failure patients. It is normally safe and effective, improving symptoms of anemia. We report here a case of renal anemia in a patient undergoing peritoneal dialysis (PD) for end stage renal failure from renovascular disease. He initially responded well to Epoetin alpha (Eprex) but subsequently developed EPO antibodies and pure red cell aplasia (PRCA), becoming blood transfusion dependent. Subsequently, he responded to Darbepoetin alpha (Aranesp), without any complications in the presence of persisting EPO antibodies. This positive response, which restored hemoglobin values to normal, occurred despite general belief that any form of EPO will cross-react to EPO antibodies. This is the first case report where PRCA with EPO antibodies responded well to another EPO preparation without intervention from immunosuppression therapy.

Topics: Aged; Aged, 80 and over; Anemia; Antibodies; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Male; Peritoneal Dialysis; Recombinant Proteins; Red-Cell Aplasia, Pure

An 80-year-old man with chronic renal failure (CRF) had pure red cell aplasia (PRCA) 9 months after starting the subcutaneous administration of recombinant human erythropoietin alfa (rHuEPO-alpha). Owing to the advanced renal failure, conventional immunosuppressive therapies were not practicable. It was decided to administer rituximab (4 cycles of 375 mg/m2/wk). PRCA was treated successfully with rituximab. The administration of rHuEPO-alpha then was resumed via the intravenous route with a satisfactory correction of anemia (12 months after the EPO-alpha rechallenge the patient is still transfusion independent). To the authors' knowledge, this is the first report of (1) a successful treatment with rituximab with CD20 depletion in a CRF patient with PRCA and (2) a successful intravenous resumption of the same rHuEPO-alpha.

Topics: Aged; Aged, 80 and over; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antigens, CD20; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Male; Recombinant Proteins; Red-Cell Aplasia, Pure; Rituximab

The sudden interruption of recombinant human erythropoietin (rHuEPO) in end-stage renal disease (ESRD) patients leads to rapid anemization. The mechanisms of this phenomenon are, however, insufficiently understood. The present study examined the response to immediate rHuEPO withdrawal in dialysis patients.. 10 chronic hemodialysis (HD) patients regularly receiving rHuEPO were studied. rHuEPO was stopped and reinitiated after 7 days. Reticulocyte profile, haemoglobin and haematocrit were measured at 0, 7 and 15 days. As a complementary study, and with the purpose of analyzying whether uremia was a relevant factor, 10 non-uremic male Wistar rats were treated with rHuEPO. After two weeks, rHuEPO was withdrawn in 5 animals, and continued for 7 additional days in the remainder. The same variables than in the human study were determined.. Changes in reticulocyte subtypes from baseline to day 7 were: total 18.2 +/- 0.9 vs 14.3 +/- 1.8% (p < 0.06); high-fluorescence (HFR): 2.6 +/- 0.4 vs 0.75 +/- 0.2 (p < 0.001); medium-fluorescence (MFR): 13.0 +/- 1.1 vs 6.6 +/- 0.9% (p < 0.02); and low-fluorescence (LFR): 84.2 +/- 1.4 vs 92.7 +/- 1% (p NS). The baseline pattern was recovered upon 7 days of rHuEPO reinitiation (p NS). Mean hemoglobin and hematocrit decreased by day 14 (p < 0.02) in spite of rHuEPO reinitiation at day 7. In non-uremic rats, changes were similar to that in the ESRD patients.. rHuEPO induces changes in the reticulocyte pattern, consisting in a reduction of immature reticulocytes. These changes appear to be independent of the presence of uremia. Accordingly, complete rHuEPO withdrawal in HD patients will cause a rapidly-developing anaemia due to an alteration in the reticulocyte maturation series; therefore, sudden rHuEPO interruption should be avoided whenever is possible. As a collateral application, the specific changes described herein have potential use for detecting illegal administration of rHuEPO.

Topics: Aged; Anemia; Animals; Doping in Sports; Drug Administration Schedule; Epoetin Alfa; Erythropoiesis; Erythropoietin; Female; Hematocrit; Humans; Kidney Failure, Chronic; Male; Middle Aged; Rats; Rats, Wistar; Recombinant Proteins; Recurrence; Renal Dialysis; Reticulocyte Count; Uremia

Topics: Anemia; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Meta-Analysis as Topic; Recombinant Proteins

Between 1988 and 1998, antibody-associated pure red-cell aplasia was reported in three patients who had undergone treatment with recombinant human erythropoietin (epoetin). Between 1998 and 2000, 13 such cases were reported from France--12 in patients who had received the Eprex formulation of epoetin alfa and 1 in a patient who had received Neorecormon (a formulation of epoetin beta); both are products that are marketed outside the United States.. We obtained reports of epoetin-associated pure red-cell aplasia from the Food and Drug Administration and from the manufacturers of Eprex, Epogen (another formulation of epoetin alfa), and Neorecormon. The numbers of case reports and estimates of exposure-adjusted incidence were analyzed according to the product, the cause of anemia, the route of administration, the country in which pure red-cell aplasia was identified, and the date on which pure red-cell aplasia was reported.. Between January 1998 and April 2004, 175 cases of epoetin-associated pure red-cell aplasia were reported for Eprex, 11 cases for Neorecormon, and 5 cases for Epogen. Over half these cases had occurred in France, Canada, the United Kingdom, and Spain. Between 2001 and 2003, the estimated exposure-adjusted incidence was 18 cases per 100,000 patient-years for the Eprex formulation without human serum albumin, 6 per 100,000 patient-years for the Eprex formulation with human serum albumin, 1 case per 100,000 patient-years for Neorecormon, and 0.2 case per 100,000 patient-years for Epogen. After procedures were adopted to ensure appropriate storage, handling, and administration of Eprex to patients with chronic kidney disease, the exposure-adjusted incidence decreased by 83 percent worldwide.. After the peak incidence of Eprex-associated pure red-cell aplasia was reached in 2001, interventions designed in response to drug-monitoring programs worldwide resulted in a reduction of more than 80 percent in the incidence of pure red-cell aplasia due to Eprex.

Topics: Adolescent; Adult; Adverse Drug Reaction Reporting Systems; Aged; Aged, 80 and over; Epoetin Alfa; Erythropoietin; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Red-Cell Aplasia, Pure

Since 1998, there has been a marked increase in incidence of pure red cell aplasia secondary to development of anti-erythropoietin antibodies (Ab+ PRCA) in patients who have chronic kidney disease (CKD) and receive recombinant erythropoietin. The relationship between incidence of Ab+ PRCA and specific erythropoietin products has not been examined rigorously. Manufacturers provided data regarding exposure to erythropoietin products and incidence of Ab+ PRCA between January 1998 and March 2003 in patients with CKD. Assuming a Poisson distribution, a maximum likelihood estimate for the Poisson rate parameter was calculated for each product. A test for homogeneity of Poisson rates was conducted to compare likelihood estimates between products. Global incidence of Ab+ PRCA was relatively low. Likelihood estimates were not significantly different for Epogen, Procrit, and Aranesp, independent of their formulation or route of administration. Eprex lacking human serum albumin (HSA) and administered subcutaneously was associated with the greatest risk of Ab+ PRCA. HSA-containing Eprex administered subcutaneously was associated with a lower risk than HSA-free Eprex administered subcutaneously, but this risk exceeded that of intravenous Epogen and intravenous HSA-free Eprex. NeoRecormon administered subcutaneously was associated with less risk than subcutaneous HSA-free Eprex but more risk than intravenous Epogen. HSA-free Eprex should not be administered subcutaneously to patients with CKD due to increased risk of Ab+ PRCA. Although the subcutaneous administration of HSA-containing Eprex is riskier than intravenous Epogen and intravenous HSA-free Eprex, and the use of subcutaneous NeoRecormon is riskier than intravenous Epogen, there is currently no evidence that other products are safer.

Topics: Age Distribution; Autoantibodies; Cohort Studies; Darbepoetin alfa; Dose-Response Relationship, Drug; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Follow-Up Studies; Health Planning Guidelines; Humans; Kidney Failure, Chronic; Male; Prevalence; Primary Prevention; Recombinant Proteins; Red-Cell Aplasia, Pure; Risk Assessment; Severity of Illness Index; Sex Distribution

Anemia is a frequent complication of end-stage renal disease. Poor responsiveness to epoetin therapy hampers the management of anemia. Escalating epoetin doses often are used to overcome epoetin resistance. The objective of this study is to examine the relationship between epoetin dose requirements and mortality.. Using United States Renal Data System administrative claims data, we conducted a retrospective cohort study of 94,569 prevalent hemodialysis patients in 2000 and 2001. A Cox proportional hazard regression analysis, adjusted for baseline variables, and a 5-knot cubic regression spline were used to model the dose-response relationship between epoetin and all-cause mortality.. Significant interpatient variation exists in epoetin dose requirements to attain defined hematocrit levels. For every hematocrit cohort studied, patients administered higher doses of epoetin had significantly lower hematocrit values and greater mortality rates. Using the cubic spline function, a significant nonlinear relationship between increased epoetin dose and mortality was found regardless of hematocrit (P < 0.0001), with the steepest increase in relative risk for death found after the 72.5th dose percentile.. Epoetin dose requirement is an independent predictor of total mortality in hemodialysis patients after adjustment for hematocrit. Poor responders who continue to have low hematocrit values despite the administration of high epoetin doses may not necessarily benefit from more epoetin, but perhaps should be considered for other adjunctive therapies. In contrast to conventional wisdom, this study suggests that epoetin dosing requirements could provide important prognostic information beyond that predicted by hematocrit alone.

Topics: Aged; Anemia; Black People; Cohort Studies; Dose-Response Relationship, Drug; Drug Resistance; Epoetin Alfa; Erythropoiesis; Erythropoietin; Female; Humans; Incidental Findings; Kidney Failure, Chronic; Male; Middle Aged; Predictive Value of Tests; Proportional Hazards Models; Recombinant Proteins; Renal Dialysis; Retrospective Studies; Sensitivity and Specificity; United States; White People

To evaluate the use of hematocrit as a surrogate end point for survival among end-stage renal disease (ESRD) patients treated with epoetin.. Using United States Renal Data System (USRDS) data, we conducted an observational prospective study to analyze the relationships among epoetin dose, hematocrit, and survival for 31,301 facility-based hemodialysis patients incident to ESRD therapy in 1998. To address our objective, we used criteria developed by Prentice based on results from a Cox regression model.. Results indicate that hematocrit is inversely associated with epoetin dose. For the same epoetin treatment-related achieved hematocrit levels, there were widely varying treatment-related survival outcomes, thereby challenging a central criterion required to empirically validate a surrogate end point.. Our results support earlier clinical trial and epidemiological data suggesting that hematocrit may not be a valid surrogate for survival among the epoetin-treated renal failure population. We hypothesize that hematocrit may not be in the causal pathway or that epoetin may have important mechanisms of action apart from increasing hematocrit. Effective treatment for anemia may therefore not be simply a matter of increasing hematocrit. This study has potential implications for revising the existing treatment guidelines for anemia management and selecting an appropriate treatment regimen.

Topics: Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Hematinics; Hematocrit; Humans; Kidney Failure, Chronic; Prospective Studies; Recombinant Proteins; Regression Analysis; Renal Dialysis; Survival Rate

To investigate effects of early correction of anemia on the rate of cardiovascular complications and survival on regular hemodialysis (RHD).. Eighty patients with chronic renal failure (CRF) on regular hemodialysis entered two groups: group 1 with hemoglobin (Hb) < 80 g/l (n = 36) and group 2 with Hb > 100 g/l (n = 44). 90% patients of group 2 were treated for renal anemia for 6-8 months of predialysis CRF. When placed on RHD, group 1 started therapy with epoetin, 39 patients of group 2 continued epoetin treatment.. Patients of group 2 had a higher rate of eccentric left ventricular hypertrophy (LVH) with reduced ejection fraction and development of congestive cardiac failure and coronary heart disease. Eccentric LVH in group 1 patients regressed only in 80% when the patients were on hemodialysis and received epoetin for correction of anemia. Overall cardiac death in group 1 was twice that of group 2 patients.. Early correction of anemia led to a 50% increase in 5-year survival. This fact can be explained with inhibited progression of eccentric LVH.

Topics: Adult; Anemia; Cardiotonic Agents; Case-Control Studies; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Ventricular Function, Left

Topics: Adult; Aged; Aged, 80 and over; Anemia; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Insurance, Health, Reimbursement; Kidney Failure, Chronic; Male; Medicare; Middle Aged; Quality of Life; Recombinant Proteins; Renal Dialysis; Sickness Impact Profile; United States

According to recommendations of exclusively intravenous administration of erythropoietin alpha (EPOalpha) produced in Europe (Eprex-Janssen-Cilag), we compared the effectiveness of EPOalpha during 6 months of the therapy after conversion from s.c. to i.v. route in 21 hemodialysed patients.. The inclusion criteria were as follows: stable blood morphology over the 3 months before conversion; haemoglobin concentration > 10.0 g/dl; transferrin saturation > 20% and serum ferritin > 200 microg/l. Dose of EPOalpha was verified every month in the course of the study, depending on actual haemoglobin concentration.. There were no significant differences in haemoglobin concentration and EPOalpha dose in all monitored time intervals. We didn't find any differences in transferrin saturation, serum albumin concentration and haemodialysis adequacy between starting values and results after 6 months of the therapy. Only values of CRP, serum ferritin concentration and iPTH were significantly higher after 6 months of i.v. EPOalpha therapy comparing to the initial data.. in hemodialysed patients with adequate iron stores and stable values of haemoglobin change of the route of EPOalpha administration from s.c. to i.v. is not connected with the increase of the dose of EPOalpha to maintain the haemoglobin values in the target range.

Topics: Aged; Epoetin Alfa; Erythropoietin; Female; Follow-Up Studies; Humans; Injections, Intradermal; Injections, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Time Factors; Treatment Outcome

Patients with end-stage renal disease requiring hemodialysis are frequently treated with epoetin alfa (recombinant human erythropoietin, rHuEPO) for anemia. The aim of this study was to determine whether successful management of anemia could be maintained by changing the dosing schedule of epoetin alfa from 2 or 3 times per week to once-weekly administration via not only the subcutaneous (s.c.) but also the intravenous (i.v.) route.. Patients included in the study had hemodialysis for > 12 months, treatment with epoetin for > or = 6 months and adequate iron stores. The study consisted of a pre-study period (12 weeks), Phase I (4 weeks, patients continued prestudy regimen), Phase II (12 weeks, once-weekly i.v. or s.c. regimen with dose adjustments permitted to maintain target hemoglobin (Hb) concentrations) and Phase III (4 weeks, once-weekly i.v. or s.c. regimen without dose adjustments).. The study was completed by 203 patients (per-protocol population: i.v. group, n = 115, s.c. group, n = 88). In the majority of patients (69.4% overall: i.v. group, 67.0%, s.c. group, 72.7%), the individual Phase I Hb concentrations were maintained within +/-1.0 g/dl (+/-10 g/l) during Phase III. In 79.3% of the patients (i.v. group, 75.7%, s.c. group, 84.1%), a stable Hb concentration (decrease of < or = 1 g/dl (< or = 10 g/l)) was maintained without statistically significant dose adjustments (82.4+/-33.8 - 86.8+/-42.1 IU/kg body weight/week). Hb concentrations decreased from 11.57+/-0.83 g/dl(115.7+/-8.3 g/l) in Phase I to 11.39+/-1.09 g/dl (113.9+/-10.9 g/l) in Phase III (p < 0.05) in the entire group. The weekly dose of epoetin alfa required to maintain the individual target Hb concentrations changed from 85.1+/-34.6 IU/kg in Phase I to 92.1+/-45.1 IU/kg in Phase III in the entire population (p <0.05).. With once-weekly administration of epoetin alfa, Hb concentrations can be maintained in the majority of stable hemodialysis patients, and only minimal dose adjustments are required.

Topics: Anemia; Cross-Over Studies; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Hemoglobins; Humans; Injections, Intravenous; Injections, Subcutaneous; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Safety

Recombinant human erythropoietin (epoetin) is widely used for correction of anaemia in patients with chronic renal disease and its efficacy has been confirmed in numerous studies. Disturbances in carnitine metabolism may also contribute to the development of renal anaemia. Although increases in erythrocyte count (RBC) and changes in RBC metabolism during L-carnitine administration have been observed, supplementation with L-carnitine in anaemic hemodialysis patients is not routine. The aim of our study was to determine the influence of epoetin on hematological parameters and plasma carnitine profile in anaemic hemodialysis patients. 36 hemodialysis patients (22 men, 14 female, aged from 17 to 64 years, mean 43) and 30 healthy volunteers (12 men, 18 female, aged from 25 to 65 years, mean 40) were studied. Epoetin (Eprex, Janssen-Cilag) was administered subcutaneously for twelve months with the starting dose 2000 IU three times per week (range from 75 to 133, mean 102 +/- 21 IU/kg/week). The target hemoglobin (Hb) range at the time of the study was between 10-11 g/dL. Laboratory markers of hematological response, carnitine and iron status, were measured before epoetin administration and then controlled every three months. During epoetin treatment a significant increase in Hb concentration was observed (100% of patients responded to epoetin). In the third and six month of epoetin treatment, along with a significant increase in mean reticulocyte count and the highest increment of RBC count and Hb levels, probably due to increased erythropoiesis, a significant, transient decrease of mean total and free plasma carnitine levels was observed. This may suggest the utilisation of carnitine by a new RBC population. It also indicates that there is a need for L-carnitine in carnitine deficient maintenance hemodialysis patients particularily during erythropoiesis induced by epoetin treatment.

Topics: Adolescent; Adult; Aged; Anemia; Carnitine; Epoetin Alfa; Erythropoietin; Female; Ferritins; Hematinics; Humans; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Reticulocyte Count

To determine the degree of anaemia corresponding to the decreasing levels of renal function in patients with chronic renal failure (CRF) and not yet on dialysis, and to assess the indications for treatment with recombinant erythropoeitin (epoetin).. We studied the relationship between haemoglobin (Hb) concentration and creatinine clearance (Ccr) in 403 consecutive patients with CRF regularly monitored in nephrology consultations between January 1 and June 30, 1999, and who received appropriate iron and vitamin supplementation. These patients were then followed-up until June 30, 2000 or until maintenance dialysis was initiated.. There was a significant and close correlation between the degree of anaemia and renal dysfunction. An Hb value<11 g/dl (corresponding to the present threshold for the indication of epoetin) was observed in 62% of patients with creatinine levels>400 micromol/l and in 58% when Ccr was<20 ml/mn/1.73 m2. Whatever the level of CRF, the degree of anaemia was higher in the women than in the men. Among the 123 patients who had to start maintenance dialysis during the observation period, 85 (69%) were treated with epoetin before dialysis was started.. In patients with CRF, clinically symptomatic anaemia is more frequent than imagined, and early treatment is required. Regular monitoring of Hb and iron levels is mandatory in order to allow patients to benefit from timely initiation of epoetin and thus prevent the development of disabling asthenia and other deleterious consequences of anaemia.

Topics: Adult; Age Factors; Aged; Analysis of Variance; Anemia; Creatinine; Epoetin Alfa; Erythropoietin; Female; Follow-Up Studies; Hematinics; Hemoglobins; Humans; Iron; Kidney Failure, Chronic; Male; Middle Aged; Multivariate Analysis; Recombinant Proteins; Renal Dialysis; Sex Factors; Time Factors

Human recombinant erythropoietin is the main treatment for anemia in renal patients. Recently, there have been case reports of pure red blood cell aplasia (PRCA) developing in renal patients administered erythropoietin, probably because of neutralizing antibodies detected in all these patients. All reports were from the West, and most patients were treated with erythropoietin-alpha. Cyclosporine is an immunosuppressive agent used to treat a spectrum of autoimmune conditions. We report a series of Chinese renal patients who developed PRCA after treatment with erythropoietin-alpha, suggesting that this is a problem worldwide. They were treated successfully with cyclosporine and became transfusion independent.

Topics: Aged; Asian People; Cyclosporine; Epoetin Alfa; Erythropoietin; Humans; Kidney Failure, Chronic; Male; Recombinant Proteins; Red-Cell Aplasia, Pure

Topics: Darbepoetin alfa; Dose-Response Relationship, Drug; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Recombinant Proteins; Renal Dialysis; Therapeutic Equivalency

Topics: Adult; Anemia; Epoetin Alfa; Erythropoietin; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Retrospective Studies; Statistics, Nonparametric; Treatment Outcome

We report the case of a woman with end-stage renal disease on maintenance hemodialysis and treated with recombinant human erythropoietin (epoetin alfa) administered subcutaneously, who developed a pure red cell aplasia secondary to the development of neutralizing antibodies anti-erythropoietin after 8 months of treatment. Despite epoetin withdrawal and immunosuppressive treatment with corticosteroids and gammaglobulins the patient still has high red blood cell transfusion requirements and undetectable plasma erythropoietin levels. Pure red cell aplasia secondary to the development of neutralizing antibodies anti-erythropoietin is a rare but severe complication associated with the use of recombinant human erythropoietin in uremic patients. In recent years, the incidence of this complication has sharply increased, specially associated with the use of epoetin alfa administered subcutaneously. For this reason, the Spanish Drug Agency has recently contraindicated treating uremic patients with epoetin alfa administered subcutaneously.

Topics: Adult; Autoantibodies; Epoetin Alfa; Erythropoietin; Female; Humans; Kidney Failure, Chronic; Recombinant Proteins; Red-Cell Aplasia, Pure; Uremia

In 2000 and 2001, The Centers for Medicare & Medicaid Services (CMS) End-Stage Renal Disease (ESRD) Clinical Performance Measures (CPM) project collected data on all in-center hemodialysis (HD) patients in the United States aged >or=12 and <18 years. There were 433 of 486 (89%) patients and 435 of 516 (84%) patients who had the minimum required data submitted and were included in the 2000 and 2001 study years, respectively. There were 188 patients (43%) who had data submitted in both study years, providing longitudinal data on this cohort. A comparison of clinical parameters on these 188 patients in the 2000 and 2001 study years reveals significant improvement in mean calculated spKt/V (1.50+/-0.36 vs. 1.58+/-0.30, P<0.01), mean hemoglobin (11.0+/-1.6 g/dl vs. 11.5+/-1.3 g/dl, P<0.001), mean ferritin (286+/-278 ng/ml vs. 460+/-353 ng/ml, P<0.001), mean transferrin saturation (27.8+/-15.1% vs. 31.3+/-15.0%, P<0.05), mean serum albumin as measured by the bromocresol green method (3.83+/-0.54 g/dl vs. 3.95+/-0.42 g/dl, P<0.01), and mean height standard deviation score (-1.814+/-1.756 vs. -1.699+/-1.657, P<0.05). In addition, 20 of 29 (69%) patients who had a spKt/V <1.2 in the 2000 study year had a spKt/V >1.2 in the 2001 study year. Of 68 (44%) patients who had a catheter as their HD access in the 2000 study year, 30 had an arteriovenous fistula or graft in the 2001 study year and 49 of 80 (61%) patients who had a mean hemoglobin <11 g/dl in the 2000 study year had a hemoglobin >11 g/dl in the 2001 study year. In summary, these longitudinal data demonstrate significant improvements in nearly all clinical parameters studied in these adolescent HD patients.

Topics: Adolescent; Adolescent Development; Anemia; Arteriovenous Shunt, Surgical; Body Height; Catheters, Indwelling; Cohort Studies; Epoetin Alfa; Erythropoietin; Female; Humans; Kidney Failure, Chronic; Longitudinal Studies; Male; Recombinant Proteins; Renal Dialysis; Serum Albumin; Treatment Outcome

Topics: Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Recombinant Proteins; Red-Cell Aplasia, Pure

Topics: Aged; Anemia; Autoantibodies; Diagnosis, Differential; Epoetin Alfa; Erythropoietin; Female; Humans; Kidney Failure, Chronic; Recombinant Proteins; Red-Cell Aplasia, Pure

Topics: Anemia; Drug Costs; Drug Industry; Epoetin Alfa; Erythropoietin; Health Expenditures; Humans; Italy; Kidney Failure, Chronic; National Health Programs; Recombinant Proteins

Anemia management protocols provide a consistent, standardized, therapeutic approach that can help nurses and other members of the nephrology team achieve more stable Hb levels within the target range of 11 to 12 g/dL recommended by the NKF-K/DOQI. This article provides an overview of Winthrop University Hospital's anemia management protocol, with a focus on an Epoetin alfa algorithm that was developed to guide therapeutic interventions.

Topics: Algorithms; Anemia; Clinical Protocols; Epoetin Alfa; Erythropoietin; Hemoglobins; Humans; Iron; Kidney Failure, Chronic; Patient Care Planning; Recombinant Proteins; Renal Dialysis

Recent data suggests that erythropoietin therapy may actually retard the progression of chronic kidney disease (CKD). Transplant recipients with evidence of chronic allograft dysfunction could respond in a similar manner to erythropoietin.. We evaluated 166 individuals who initiated erythropoietin therapy after at least 18 days of transplant function. One hundred and nine individuals received erythropoietin between days 18 and 294 of transplant function (group 1-early epoietin alfa) while 57 individuals received erythropoietin on or after day 294 of transplant function (group 2-late epoietin alfa). The slope of serum creatinine (Scr) (Deltaslope Scr) prior to and following the start of erythropoietin therapy and calculated glomerular filtration rates (GFR) were used to assess renal function over time.. The average haematocrit rose 6.6% in group 1 patients and 2.1% in group 2 patients during the first 100 days of erythropoietin therapy. The Deltaslope Scr was not significantly altered in group 1 patients. However, for group 2 individuals who continued to have graft function (n=35), the Deltaslope Scr became negative during erythropoietin treatment. This indicated a deceleration in the rate of loss of renal function (day 200 Deltaslope Scr -0.0033, P=0.00091; day 300 Deltaslope Scr -0.0014, P=0.05; day 400 Deltaslope Scr -0.0066, N.S., P=0.066). GFR remained stable in both cohorts. Finally, group 2-late epoietin alfa patients treated with erythropoietin demonstrated a marked trend towards longer graft survival than a group of similar control patients (N.S., P=0.064).. The data in a group of renal transplant recipients with chronic allograft dysfunction reinforce data from the CKD realm suggesting that erythropoietin may be of benefit in slowing the rate of loss of function over time. However, this renal response is not evident in all patients. Prospective studies of erythropoietin or erythropoietin-like medications are warranted in this population to better discriminate those who may respond well to administration of these drugs.

Topics: Adult; Creatinine; Databases, Factual; Epoetin Alfa; Erythropoietin; Female; Graft Survival; Hematocrit; Humans; Iron Deficiencies; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Recombinant Proteins; Retrospective Studies; Time Factors

Topics: Darbepoetin alfa; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Humans; Kidney Failure, Chronic; Recombinant Proteins; Therapeutic Equivalency

New patients starting dialysis typically have hemoglobin (Hb) and hematocrit (Hct) levels well below the target range of 11 to 12 g/dL (33% to 36%) recommended by the NKF-K/DOQI. Despite the emphasis on anemia as a quality indicator, low Hb levels often persist for months after dialysis is initiated. Several factors can help promote timely correction of anemia. (a) proactively assessing anemia-related laboratory indicators, (b) calculating weight-based Epoetin alfa starting doses, (c) starting Epoetin alfa therapy on the first day of dialysis for all eligible patients, and (d) proactively assessing patients for conditions that may affect the erythropoietic response. Through proactive, protocol-mandated interventions, nurses can help ensure that anemia is corrected promptly.

Topics: Anemia, Iron-Deficiency; Drug Monitoring; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hematocrit; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Nursing Assessment; Recombinant Proteins; Renal Dialysis

Topics: Antibodies; Epoetin Alfa; Erythropoietin; Humans; Kidney Failure, Chronic; Receptors, Erythropoietin; Recombinant Proteins; Red-Cell Aplasia, Pure

Anemia is a common complication of advancing chronic kidney disease, yet little is known about the consistency of anemia treatment before end-stage renal disease (ESRD) and mortality on dialysis therapy.. We studied 89,193 incident Medicare patients with ESRD in 1995 to 1997 aged 67 plus years with claims 2 years before their dialysis therapy initiation. Patients were classified as follows: no epoetin, 25% or less (least consistent), greater than 25% to 50%, greater than 50% to 75%, and greater than 75% (most consistent) epoetin treatment in the available months from the first pre-ESRD epoetin dose to the first ESRD service date. Cox regression modeled the risk for 1-year death in the post-ESRD period, adjusting for age, sex, race, diabetic status, albumin level, and incidence year.. Sixty percent of patients had hematocrits less than 30% at ESRD initiation, yet only 15.6% (N = 13,877) had epoetin claims before ESRD. The most consistent epoetin treatment group had hematocrits increase from 27.5% to 30.8% (P < 0.0001) by month 4 of treatment. Patients with the most consistent epoetin treatment had a greater mean hematocrit (29.2% +/- 0.11%; P < 0.0001) and albumin level (3.31 +/- 0.01 g/dL [33.1 g/L]) at initiation than those with the least consistent treatment (28.1% +/- 0.10% and 3.21 +/- 0.01 g/dL [32.1 g/L], respectively). The relative risk for death in patients with the least consistent versus the most consistent (the reference) epoetin treatment was 1.460 (95% CI, 1.245 to 1.713; P < 0.0001) 1 year after the first ESRD service date.. Elderly patients with consistent pre-ESRD epoetin treatment had lower risks for death in the first year of dialysis therapy after ESRD initiation.

Topics: Aged; Anemia; Diabetes Complications; Diabetes Mellitus; Drug Administration Schedule; Epoetin Alfa; Erythrocyte Indices; Erythropoietin; Female; Hematocrit; Humans; Kidney Failure, Chronic; Male; Models, Statistical; Mortality; Racial Groups; Recombinant Proteins; Renal Dialysis; Reproducibility of Results; Serum Albumin; Sex Factors; Survival Rate

Within a period of three years, we identified 13 patients in whom pure red-cell aplasia developed during treatment with recombinant human erythropoietin (epoetin). We investigated whether there was an immunologic basis for the anemia in these patients.. Serum samples from the 13 patients with pure red-cell aplasia were tested for neutralizing antibodies that could inhibit erythroid-colony formation by normal bone marrow cells in vitro. The presence of antierythropoietin antibodies was identified by means of binding assays with the use of radiolabeled intact, deglycosylated, or denatured epoetin.. Serum from all 13 patients blocked the formation of erythroid colonies by normal bone marrow cells. The inhibition was reversed by epoetin. Antibodies from 12 of the 13 patients bound only conformational epitopes in the protein moiety of epoetin; serum from the remaining patient bound to both conformational and linear epitopes in erythropoietin. In all the patients, the antibody titer slowly decreased after the discontinuation of treatment with epoetin.. Neutralizing antierythropoietin antibodies and pure red-cell aplasia can develop in patients with the anemia of chronic renal failure during treatment with epoetin.

Topics: Adult; Aged; Aged, 80 and over; Autoantibodies; Bone Marrow Cells; Cell Division; Epoetin Alfa; Erythroid Precursor Cells; Erythropoietin; Humans; Iodine Radioisotopes; Kidney Failure, Chronic; Middle Aged; Recombinant Proteins; Red-Cell Aplasia, Pure

Topics: Autoantibodies; Autoimmune Diseases; Epoetin Alfa; Erythropoietin; Humans; Kidney Failure, Chronic; Recombinant Proteins; Red-Cell Aplasia, Pure

The management of anemia in adult end-stage renal disease (ESRD) patients receiving hemodialysis in dialysis facilities is examined. Clinical information was collected for a random sample of adult (age > or = 18 years) patients who received hemodialysis for ESRD between October and December 1999 and included hemoglobin concentrations, epoetin alfa doses and routes of administration, iron prescribing patterns, transferrin saturation levels, and serum ferritin concentrations. Patients whose data did not include hemoglobin concentrations with the weekly epoetin dose were excluded from the analysis. Associations by patient characteristics and geographic region were examined for clinical intermediate outcomes and epoetin alfa and iron prescribing practice patterns. Data were submitted for 8154 patients, and hemoglobin values linked to weekly epoetin alfa doses were available for 7573 of those patients. The mean hemoglobin concentration for patients in the sample was 11.4 +/- 1.3 g/dL. Sixty-seven percent of patients had mean hemoglobin values > or = 11 g/dL. Females, blacks, patients 18-44 years old, and patients receiving hemodialysis for less than six months exhibited significantly lower mean hemoglobin values despite being prescribed, on average, significantly higher epoetin alfa doses than males, whites, older patients, and patients receiving hemodialysis for six months or more (p < 0.001). There was significant regional variation in the prescribing patterns for s.c. epoetin alfa and i.v. iron (p < 0.001). Multivariable logistic regression analysis found significant associations between mean hemoglobin values > 11 g/dL and certain patient characteristics, including white race, hemodialysis for six months or longer, lower prescribed weekly epoetin alfa doses, prescription of i.v. iron, mean transferrin saturation levels > or = 20%, mean Kt/V > or = 1.2, and higher mean serum albumin values. Prescribing patterns for i.v. iron did not vary by the status of patients' iron stores. Regional and patient-specific variations in parameters of anemia management provide pharmacists with the opportunity to contribute to a multidisciplinary team approach to improve the care of hemodialysis patients.

Topics: Adult; Aged; Anemia, Iron-Deficiency; Epoetin Alfa; Erythropoietin; Female; Ferritins; Hematinics; Hemoglobins; Humans; Iron; Kidney Failure, Chronic; Logistic Models; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Risk Factors; Transferrin; Treatment Outcome

Chronic kidney disease (CKD) is a growing public health problem. Morbidity and mortality rates from CKD and end-stage renal disease remain high despite the advent of new knowledge, therapies, and clinical practice guidelines. Consequently, the reasons for the underdiagnosis and undertreatment of CKD must be addressed and appropriate preventive and therapeutic interventions implemented. Managed care organizations (MCOs) can facilitate this process by implementing intervention programs that target clinicians and patients with kidney disease. These programs should promote 1) early detection of CKD and comorbid conditions; 2) use of appropriate outcome measures to stratify patient care; 3) implementation of strategies to delay disease progression and prevent or treat complications; and 4) adequate preparation for and timely initiation of renal replacement therapy. Early detection and proactive care of predialysis patients not only improve outcomes and quality of life, but also reduce costs for society and MCOs.

Topics: Anemia; Darbepoetin alfa; Education, Medical, Continuing; Epoetin Alfa; Erythropoietin; Glomerular Filtration Rate; Hematinics; Humans; Kidney Failure, Chronic; Managed Care Programs; Mass Screening; Practice Guidelines as Topic; Preventive Health Services; Quality Assurance, Health Care; Quality Indicators, Health Care; Recombinant Proteins; Renal Dialysis; United States

Topics: Anemia; Animals; Epoetin Alfa; Erythropoietin; Humans; Kidney Failure, Chronic; Recombinant Proteins

This study was undertaken to describe the relationship between hematocrit (Hct) and changes in the prescribed dose of erythropoietin (EPO) as well as selected patient and process care measures across annual national samples of hemodialysis patients from 1994 to 1998. This study uses the cohorts identified in the ESRD Core Indicators Project, random samples of 6181, 6241, 6364, 6634, and 7660 patients, stratified by ESRD Networks drawn for each year from 1994 to 1998. Patient demographic and clinical information was collected from October to December for each year. Surrogates of iron stores and patterns of iron and EPO administration were profiled from 1996 to 1998. Multivariable stepwise linear regression analyses were performed to adjust for potential confounding variables and to identify independent variables associated with Hct and EPO dose. Mean Hct and EPO dose increased each year from 31.1 +/- 5.2% to 34.1 +/- 3.7% and from 58.2 +/- 41.8 U/kg to 68.2 +/- 55.0 U/kg, respectively (P = 0.0001). Increasing Hct was positively associated with male gender, more years on dialysis, older age, higher urea reduction ratio and transferrin saturation, prescription of intravenous iron, and lower ferritin and EPO dose in multivariable models (all P = 0.0001). Male gender, older age, diabetes, higher Hct, and increasing weight, urea reduction ration, and transferrin saturation were associated with lower EPO doses (all P < 0.01). Conversely, intravenous EPO and iron were associated with higher prescribed EPO doses (all P = 0.0001). Although increasing Hct is associated with decreasing EPO dose at the patient level, the increase in Hct seen across years among the cohorts of hemodialysis patients in the United States has been associated with increasing doses of EPO at the population level.

Topics: Anemia; Epoetin Alfa; Erythropoietin; Female; Ferritins; Hematinics; Hematocrit; Humans; Iron; Kidney Failure, Chronic; Male; Quality Indicators, Health Care; Recombinant Proteins; Renal Dialysis; Serum Albumin; Transferrin; United States

Topics: Anemia; Epoetin Alfa; Erythropoietin; Hematinics; Hematocrit; Humans; Kidney Failure, Chronic; Recombinant Proteins; Renal Dialysis

Topics: Adverse Drug Reaction Reporting Systems; Anemia; Epoetin Alfa; Erythropoietin; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Red-Cell Aplasia, Pure; United States

Chronic renal failure (CRF) is associated with prolonged bleeding time and impaired platelet adhesion and aggregation. Erythropoietin (Epo) administration improves platelet adhesion/aggregation and ameliorates prolongation of bleeding time in CRF. However, the mechanisms of improved platelet function after Epo therapy have not been fully elucidated. The present study examined the hypothesis that the improved uraemic platelet function after Epo therapy is, in part, due to correction of the platelet calcium signalling.. Rats were randomized into four groups after 5/6 nephrectomies to produce CRF. The Epo-treated CRF group received Epo, 150 U/kg, twice weekly for 6 weeks to prevent anaemia; the felodipine and Epo-treated CRF group received Epo but was kept normotensive by felodipine treatment; the placebo-treated CRF group received placebo injections and became anaemic; and the iron-deficient CRF group received Epo but was kept anaemic by dietary iron-deficiency. A group of sham-operated rats was included as normal control. Basal and thrombin-stimulated platelet cytosolic calcium ([Ca(2+)](i)) were determined using a Ca(2+)-sensitive dye (fura-2).. Platelets from placebo-treated CRF group exhibited a profound attenuation of thrombin-stimulated surge in [Ca(2+)](i), which is the final pathway of platelet activation. Long-term Epo administration led to a normalization of the thrombin-induced rise in platelet [Ca(2+)](i) in the CRF animals, independent of either haematocrit or blood pressure values. Further studies revealed that improved Ca(2+) signalling with Epo is associated with increased Ca(2+) uptake and expanded Ca(2+) stores in the platelets.. The defective Ca(2+) signalling in uraemic animals and its improvement with chronic Epo therapy provides the biochemical basis of the previously reported platelet dysfunction and prolonged bleeding time in uraemic patients and animals, and their amelioration with chronic Epo therapy.

Topics: Animals; Blood Pressure; Calcium; Calcium Signaling; Creatinine; Cytosol; Epoetin Alfa; Erythropoietin; Hematinics; Hematocrit; Humans; Kidney Failure, Chronic; Male; Platelet Aggregation; Rats; Rats, Sprague-Dawley; Recombinant Proteins; Signal Transduction; Uremia

The aim of this study was to identify the factors determining the circulating soluble transferrin receptor (sTfR) concentrations in haemodialysis (HD) patients on maintenance recombinant human erythropoietin (rHuEpo) treatment.. In a prospective cross-sectional study, 91 chronic HD patients and 18 anaemic controls with normal renal function were recruited. For each subject, blood samples were measured for complete blood count, reticulocyte count, percentage of hypochromic red cells (% HRC), serum ferritin, serum iron, transferrin saturation (TS), serum erythropoietin (sEpo), C-reactive protein (CRP), and sTfR. HD patients received constant rHuEpo doses and basal sEpo was measured > or = 86 h after the last injection. The age, gender, dialysis vintage, and the above-mentioned parameters were used as independent variables and logarithmic sTfR (log(10)sTfR) as a dependent variable in the forward stepwise multiple regression model.. HD patients were similar to controls regarding haematocrit, serum ferritin, TS, and % HRC, but had significantly lower sTfR, sEpo, and reticulocyte index. Univariate analyses showed that the sTfR level strongly correlated with sEpo (r=0.60, P<0.001) and % HRC (r=0.60, P<0.001), and significantly with serum ferritin (r=-0.29, P<0.01), TS (r=-0.27, P<0.05), and dose of rHuEpo administered (r=0.27, P<0.05) in HD patients. sTfR also had a positive correlation with haematocrit (r=0.26, P<0.05), red blood cell (RBC) count (r=0.23, P<0.05), and reticulocyte count (r=0.24, P<0.05), but not with CRP (r=0.16, P>0.05). Multivariate regression analysis disclosed that sEpo, HRC, and serum ferritin were the independent predictors of sTfR level. Overall, the model explained 58.8% of the variability in sTfR (R(2)=0.588, P<0.001).. Circulating sTfR is a good index of marrow erythropoietic activity in HD patients during rHuEpo treatment. Its level is also independently up-regulated by functional iron deficiency in the process of enhanced erythropoiesis. Our study showed that sTfR levels quantitatively reflect the integrated effects of iron availability, iron reserves, and erythropoietic stimulation.

Topics: Biomarkers; Cohort Studies; Cross-Sectional Studies; Epoetin Alfa; Erythropoiesis; Erythropoietin; Female; Hematinics; Humans; Iron; Kidney Failure, Chronic; Male; Middle Aged; Receptors, Transferrin; Recombinant Proteins; Regression Analysis; Renal Dialysis

Topics: Anemia; Combined Modality Therapy; Epoetin Alfa; Erythropoietin; Female; Humans; Kidney Diseases; Kidney Failure, Chronic; Male; Peritoneal Dialysis; Recombinant Proteins; Renal Dialysis

The National Kidney Foundation's Dialysis Outcome Quality Initiative (NKF-DOQI) guidelines recommend that epoetin alfa should be administered by the subcutaneous route in hemodialysis patients. We determined whether hematocrit levels in hemodialysis patients differed by route of epoetin alfa administration after controlling for demographic factors and iron status. Data were available for 7,092 of the 7,658 patients randomly chosen for inclusion in the 1997 Health Care Financing Administration Core Indicators sample. Epoetin alfa was administered to 96% of the study cohort and was administered subcutaneously in 10% of patients. After controlling for hematocrit, patient characteristics, adequacy of dialysis, iron status, serum albumin, postdialysis weight, and duration of dialysis, the epoetin alfa dose by the intravenous route was 193.6 units/kg/wk (95% confidence interval, 189.5 to 197.8 units/kg/wk) compared with 167.4 units/kg/wk (95% confidence interval, 153.9 to 180.8 units/kg/wk) for the subcutaneous route (P < 0.001). The mean hematocrit for the subcutaneous route was 32.7% +/- 3.4% and for the intravenous route was 33.0% +/- 3.2% (P < 0.05). Factors independently associated with increased hematocrit included male gender, white race, older patient age, greater number of years on dialysis, higher serum albumin concentration, higher urea reduction ratio, and percent transferrin saturation (all P < 0.001). After controlling for patient factors and weekly epoetin alfa dose, there was no association between route of epoetin alfa administration and hematocrit level (P = 0.144). Patients receiving epoetin alfa by the subcutaneous route had comparable hematocrit values using a lower epoetin alfa dose than patients receiving epoetin alfa intravenously. These data support the NKF-DOQI recommendation that epoetin alfa be administered subcutaneously in long-term hemodialysis patients.

Topics: Age Factors; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hematocrit; Humans; Injections, Intravenous; Injections, Subcutaneous; Kidney Failure, Chronic; Male; Middle Aged; Practice Guidelines as Topic; Recombinant Proteins; Regression Analysis; Renal Dialysis

Topics: Algorithms; Anemia; Clinical Protocols; Epoetin Alfa; Erythropoietin; Hematinics; Hematocrit; Humans; Iron; Kidney Failure, Chronic; Patient Care Team; Pharmacists; Program Evaluation; Recombinant Proteins; Renal Dialysis; Retrospective Studies; Statistics, Nonparametric; Transferrin; Treatment Outcome

Nephrology nurses who manage the anemia of end-stage renal disease (ESRD) are often responsible for monitoring, assessing, and intervening to maintain hemoglobin (Hb) and hematocrit (Hct) levels within their facility target range. Consistency in anemia-related outcomes is sometimes compromised when patients exhibit hyporesponse to Epoetin alfa therapy-defined as a temporary or chronic Hb/Hct level below the target range. Early detection of hyporesponse and correction of conditions that are affecting erythrocyte development can sometimes be delayed if clinicians are unable to promptly identify a causative etiology. This article reviews a hyporesponse algorithm worksheet that nurses can use to identify the cause(s) of hyporesponse and guide clinical decision making.

Topics: Aged; Algorithms; Anemia, Iron-Deficiency; Decision Trees; Drug Monitoring; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hematocrit; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Nurse's Role; Nursing Assessment; Recombinant Proteins; Renal Dialysis; Risk Factors; Treatment Failure

The Health Care Financing Administration's End-Stage Renal Disease (ESRD) Core Indicators Project collects clinical information on prevalent adult patients receiving in-center hemodialysis (HD) care in the United States to assess the quality of care delivered. Although hematocrit values, transferrin saturations, and iron prescription practices have improved over the last five years, we sought to determine whether continued opportunities for improvement of this domain of care exist.. A random sample of 7292 adult in-center HD patients was selected. Dialysis facility staff provided clinical information for the period of October through December 1996 for 6858 (94%) patients; complete laboratory information was available from 4991 (73%) returned forms. Hematocrit values, transferrin saturations, serum ferritin concentrations, epoetin alfa dosing, and iron prescriptions were abstracted from patient medical records to assess anemia management practices.. The mean hematocrit for this cohort was 32.6 +/- 3.5%. Seventy-two percent of patients had hematocrit values> 30%. Forty-two percent had hematocrit values of 33 to 36%, and 10% were severely anemic (hematocrit <28%). Ninety-four percent of the patients received epoetin alfa intravenously (i.v.) and 6% subcutaneously. The mean weekly dose was 202.4 +/- 137.2 units/kg. The mean transferrin saturation was 27.4 +/- 12.6%; 73% of patients had a mean transferrin saturation > or = 20%. The mean serum ferritin concentration was 386 +/- 422 ng/mL; 79 and 12% of patients had a serum ferritin concentration of> 100 and> 800 ng/mL, respectively. Nine percent of the sample (N = 434) had a transferrin saturation <20% and serum ferritin concentration <100 ng/mL. Regardless of the patient's transferrin saturation, approximately three fourths of the patients received either oral or i.v. iron, and only approximately one half of the patients received i.v. iron. Of the subset of patients with transferrin saturation <20% and serum ferritin concentration <800 ng/mL, only 53% were prescribed intravenous iron. Multivariate linear regression analysis revealed that serum albumin, urea reduction ratio, age, and transferrin saturation were significantly positively associated with hematocrit. Epoetin alfa dose and serum ferritin concentration were significantly and negatively associated with the hematocrit (P < 0.001).. Although substantial improvements have been made in anemia management for adult in-center HD patients over the past five years, significant opportunities persist to improve iron prescription practices.

Topics: Adult; Aged; Ambulatory Care; Anemia; Epoetin Alfa; Erythropoietin; Female; Ferritins; Hematinics; Hematocrit; Humans; Iron; Kidney Failure, Chronic; Male; Middle Aged; Multivariate Analysis; Quality Indicators, Health Care; Recombinant Proteins; Renal Dialysis; Serum Albumin; Transferrin; United States

A large, 4-year, retrospective study of the HCFA end-stage renal disease (ESRD) claims database, Parts A and B, was conducted to determine the association between hematocrit (Hct) level and survival in patients on hemodialysis. Patients who survived the last 6 months of each year and had at least 4 Epoetin alfa claims qualified for the study. Cohort entry years were 1990 through 1993, with the relative risk (RR) of mortality evaluated during the following year. Patients were stratified into four groups on the basis of mean Hct levels in the 6-month entry period: < 27%, 27% to < 30%, 30% to < 33%, and 33% to 36%. Using the 30% to < 33% Hct group as reference (relative risk (RR) = 1), patients whose mean 6-month Hct was in the 33% to 36% range were associated with significantly lower RR of mortality, while patients whose mean 6-month Hct was below 30% were associated with significantly higher RR of mortality. This epidemiologic study highlighted an important association between higher hematocrits in hemodialysis patients and lower RR of mortal.

Topics: Anemia, Iron-Deficiency; Centers for Medicare and Medicaid Services, U.S.; Cohort Studies; Comorbidity; Epidemiologic Studies; Epoetin Alfa; Erythropoietin; Hematinics; Hematocrit; Hemoglobins; Hospitalization; Humans; Insurance Claim Reporting; Kidney Failure, Chronic; Medicare; Nurse's Role; Proportional Hazards Models; Recombinant Proteins; Renal Dialysis; Retrospective Studies; Risk Factors; Severity of Illness Index; Survival Analysis; Survival Rate; United States

Topics: Abdominal Pain; Adult; Analgesics, Non-Narcotic; Anemia, Iron-Deficiency; Appendicitis; Epoetin Alfa; Erythropoietin; Fever; Gastrointestinal Hemorrhage; Glomerulonephritis; Hematinics; Humans; Hypertension; Ibuprofen; Kidney Failure, Chronic; Male; Nursing Diagnosis; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis; Recombinant Proteins; Renal Dialysis

Topics: Anemia; Antineoplastic Agents; Child; Child, Preschool; Epoetin Alfa; Erythropoietin; Humans; Infant; Infant, Newborn; Infant, Premature; Iron; Kidney Failure, Chronic; Neoplasms; Radiotherapy; Recombinant Proteins

Documentation is an integral part of good anemia management. In addition to relaying vital clinical information, documentation demonstrates how nurses and other medical professionals are striving to achieve the standards of care mandated by law, their profession, third party payers, and individual health care providers. Proper documentation of anemia management practices should include a written chronological history of the rationales, plans, interventions, and evaluations initiated to achieve patient-specific Hb/Hct target levels across the spectrum of care.

Topics: Anemia; Documentation; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Kidney Failure, Chronic; Middle Aged; Recombinant Proteins

Topics: Anemia; Cost Savings; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Recombinant Proteins; Specialties, Nursing

I.v. ascorbic acid has been used in an effort to mobilize ferritin stores in hyporesponsive HD patients receiving Epoetin alfa. However, not all patients who respond to i.v. ascorbic acid therapy will have subsequent decline in feritin stores (Gastaldello et al., 1995; Tarng & Huang, 1998). Additionally, predicting those patients who will overcome their Epoetin alfa hyporesponsiveness remains unclear. Ascorbic acid's effect on hemosiderin deposits may be another possible mechanism to the increased Epoetin alfa response observed in some HD patients (Hemosiderin is a pathologic deposition of iron in tissues including the spleen, small intestine, and bone marrow). Although there are no well-controlled studies evaluating hemosiderin and i.v. ascorbic acid, it should be noted that subjects with scurvy often present with excessive iron deposits in the tissues, indicating the possible effects of ascorbic acid on hemosiderin metabolism (Bothwell et al., 1964). Ascorbic acid deficiency is often present in many HD patients due to its removal during dialysis and lack of dietary intake (Ponka & Kuhlback, 1983). It remains controversial whether oral ascorbic acid supplementation is indicated in patients receiving HD. Therefore, the Recommended Daily Allowance (RDA) of 60 mg/day should be advised (Makoff, 1999). I.v. ascorbic acid should be considered as a possible adjuvant to therapy in patients who are "iron-overloaded" and hyporesponsive to Epoetin alfa. Although the long-term effects of i.v. ascorbic acid on HD patients is unknown, the potential risk of secondary oxalosis should be considered (Costello, 1991; Pru, Eaton, & Kjellstrand, 1985). It may be necessary to monitor plasma oxalate levels if long-term therapy with i.v. ascorbic acid is used. Clinical studies have examined i.v. ascorbic acid doses from 300 mg-500 mg given up to TIW for a maximum duration of 12 weeks without any significant deleterious effects (Gastaldello et al., 1995; Tarng & Huang, 1998; Tarng et al., 1999). However, large-scale, prospective, and controlled trails are needed to determine the long-term safety and efficacy of i.v. ascorbic acid therapy in iron overloaded HD patients receiving Epoetin alfa.

Topics: Anemia; Antioxidants; Ascorbic Acid; Drug Therapy, Combination; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Recombinant Proteins

Carnitor use for carnitine deficiency in chronic renal failure is a multidisciplinary management issue. This medication and its usefulness needs require further nursing investigation.

Topics: Aged; Aged, 80 and over; Anemia; Carnitine; Drug Resistance; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Male; Nursing Diagnosis; Recombinant Proteins; Renal Dialysis

The HCFA ESRD Core Indicators Project is designed to assess several key indicators of care in peritoneal dialysis patients, including anemia management. Information on hematocrit levels, epoetin alfa dosing, estimates of iron stores, and iron therapy as obtained in a national sample of 1,219 peritoneal dialysis patients are described. The average hematocrit was 32.8% +/- 3.8%, and severe anemia (hematocrit < 25%) occurred in 1.4% of PD patients. The mean weekly epoetin alfa dose was 134.6 U/kg. In general, there was an inverse relationship between hematocrit and epoetin alfa doses. Most (83%) of PD patients received iron therapy, with only 8% of patients receiving intravenous iron. The mean serum ferritin was 303 ng/mL, with 64% of patients having a ferritin greater than 100 ng/mL. The mean transferrin saturation was 28%, with 60% of patients having a value of less than 20%. There was an inverse relationship between serum ferritin levels and hematocrit but no relationship between hematocrit and transferrin. It is concluded that there could be improvement in the epoetin alfa and iron management in many patients.

Topics: Adolescent; Adult; Aged; Anemia; Epoetin Alfa; Erythropoietin; Female; Ferritins; Hematinics; Hematocrit; Humans; Iron; Kidney Failure, Chronic; Male; Middle Aged; Peritoneal Dialysis; Recombinant Proteins; Transferrin

Pharmacokinetic studies of intraperitoneal (IP) epoetin alfa administered to continuous ambulatory peritoneal dialysis (CAPD) patients have shown low bioavailability, primarily attributable to the dilutional effect of coadministered dialysate. However, bioavailability is improved by instilling the dose into a dry peritoneum. The current study was designed to determine whether absorption after administration into a dry peritoneum is improved by extending the dry dosing period from 4 to 8 hours. The pharmacokinetics of a single 100-unit/kg IP epoetin alfa dose were studied in 8 noninfected CAPD patients. The dose was instilled into a dry peritoneum via the peritoneal catheter and allowed to dwell for 8 hours. CAPD was then resumed. Blood samples were collected for 96 hours after the dose. A 14-hour effluent dialysate sample was collected to determine epoetin alfa recovery. Enzyme immunoassay was used for epoetin alfa analysis of serum and effluent. Standard pharmacokinetic methods were employed for analysis of the serum concentration time data. The extent of epoetin alfa absorption was significantly greater than previously reported for a 4-hour dry dwell. The mean (+/-SD) dose-normalized area-under-the-curve (nlAUC(0-infinity)) using the 8-hour dry dwell dosing technique was 6,331 +/- 2,536 mIU. h/mL. This is significantly greater than the value of 2,589 +/- 1,450 mIU. h/mL (two-sided P value = 0.002) from a previous study in which patients received the same 100-unit/kg dose using a 4-hour dry dwell. The absorption of epoetin alfa administered by the intraperitoneal route is improved by extending the time the dose resides in a dry peritoneum.

Topics: Adolescent; Adult; Aged; Biological Availability; Dose-Response Relationship, Drug; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Humans; Injections, Intraperitoneal; Kidney Failure, Chronic; Male; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Recombinant Proteins; Treatment Outcome

The Health Care Financing Administration (HCFA) End-Stage Renal Disease (ESRD) Core Indicators Project collects clinical information on prevalent adult patients receiving in-center hemodialysis care in the United States to assess the quality of care delivered. Although hematocrit values, transferrin saturations (TSATs) and iron prescription practices have improved over the last 5 years, we sought to determine whether there are continued opportunities for improvement of this domain of care. A random sample of 7,292 adult in-center hemodialysis patients was selected for the period October through December 1996. Hematocrit values, TSATs, serum ferritin concentrations, epoetin-alfa dosing, and iron prescriptions were abstracted from 4,991 patient medical records to assess anemia management practices. The mean hematocrit for this cohort was 32.6% +/- 3.5%, and 72% of patients had hematocrit values greater than 30%. Ninety-four percent of patients received epoetin alfa intravenously, with a mean weekly epoetin dose of 202.4 +/- 137.2 U/kg. The mean TSAT was 27.4% +/- 12.6%; 73% of patients had TSATs >/= 20%. The mean serum ferritin concentration was 386 +/- 422 ng/mL; 79% and 12% of patients had serum ferritin concentrations greater than 100 ng/mL and greater than 800 ng/mL, respectively. Nine percent of the sample had TSATs less than 20% and serum ferritin concentrations less than 100 ng/mL. Regardless of the TSAT, approximately three fourths of patients received iron; only about half received IV iron. Of the subset of patients with TSATs less than 20% and serum ferritin concentration less than 800 ng/mL, only 53% were prescribed IV iron. Although substantial improvements have been made in anemia management in hemodialysis patients over the last 5 years, significant opportunities persist to improve iron prescription practices.

Topics: Adult; Aged; Anemia, Iron-Deficiency; Epoetin Alfa; Erythropoietin; Female; Ferritins; Hematinics; Hematocrit; Humans; Iron; Kidney Failure, Chronic; Male; Middle Aged; Quality Indicators, Health Care; Recombinant Proteins; Renal Dialysis; Transferrin; United States

Topics: Drug Costs; Epoetin Alfa; Erythropoietin; Health Facility Administrators; Hematinics; Humans; Kidney Failure, Chronic; Medicare; Recombinant Proteins; Reimbursement Mechanisms; Societies, Scientific; United States

Even with the reservations that exist regarding the accuracy of tools to measure quality of life, there is little doubt that epoetin has dramatically improved the quality of life in patients with the anemia of chronic renal failure. Patients feel better and have increased energy levels, greater capacity for physical exercise, fewer symptoms of lethargy and tiredness, improved memory and concentration, and less angina and breathlessness. Cardiac, sexual, and cognitive functions all improve, and quality of life assessments suggest enhancements in both physical and social aspects of well-being. Furthermore, circumstantial evidence suggests that treatment with epoetin is quite likely to reduce cardiovascular morbidity and mortality in patients with renal anemia. While chronic anemia has common characteristics irrespective of the etiology, the implications on quality of life in patients with chronic renal failure vary in a number of ways from those in patients with cancer.

Topics: Anemia; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Neoplasms; Quality of Life; Recombinant Proteins

Topics: Anemia; Epoetin Alfa; Erythropoietin; Hematocrit; Humans; Iron; Kidney Failure, Chronic; Recombinant Proteins; Renal Dialysis

The cost-effectiveness impact of iron dextran administration on the use of epoetin alfa and blood in hemodialysis patients was studied. Subjects were ambulatory hemodialysis patients who had been receiving hemodialysis for at least six months before the start of an iron dextran protocol and who had been given epoetin alfa for at least four of those six months. Clinical data were collected for six months before and six months after the protocol was implemented. Successful treatment was defined as a hematocrit of 33-36%, a transferrin saturation of >10%, a ferritin concentration of >100 ng/mL, and no blood use except for acute blood loss. A total of 33 patients completed the study. Fifty units of blood were used in the first six months and nine units in the second six months. There was significant improvement in mean hematocrit, ferritin, and transferrin saturation values after the protocol began. Average epoetin alfa doses did not change significantly. There was significant improvement in success rates for ferritin and blood use and in the overall success rate. Ten patients met all success criteria in the preprotocol period, versus 27 in the postprotocol period. Monthly cost-effectiveness analysis for the preprotocol and postprotocol periods indicated costs of $1350 and $526, per successful treatment, respectively. The incremental cost-effectiveness of iron dextran was $42 per successful treatment. Iron dextran improved iron indices and reduced the need for blood transfusions but did not reduce the average dose of epoetin alfa. The additional cost of therapy per month seemed justified by the clinical benefits.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Blood Transfusion; Cost-Benefit Analysis; Epoetin Alfa; Erythropoietin; Female; Ferritins; Hematinics; Hematocrit; Humans; Idaho; Iron-Dextran Complex; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Transferrin

Guidelines for the treatment of anemia in chronic renal failure (CRF) patients were recently published by NKF-DOQI. The background was provided by the fact that anemia in CRF patients fulfills all the criteria requested for the outlining of guidelines. In fact: 1) anemia is a clinically relevant problem for CRF patients; 2) it may be prevented by adequate erythropoietin (EPO) therapy; 3) a great variability in its management exists, not only concerning the optimal hematocrit (HCT) level, but also the treatment schedule as well as iron supplementation. More than eight hundred forty five scientific articles were retrieved in full text, eventually leading to 530 structurally reviewed papers (349 cited in the final text) thus providing the basis for the strength of recommendations (evidence or opinions): all topics were subdivided into 7 main issues (diagnostic and therapeutic). Main results were the following: HCT, hemoglobin (Hb), red blood cell, serum iron binding capacity, percent transferrin saturation (TSAT) and serum ferritin (FERR), to evaluate the degree of anemia and iron status; HCT 33 to 36% and Hb 11 to 12 g/dl as possible target levels; TSAT >20% and FERR >100 ug/dl as acceptable lower values for iron status; oral iron administration not <200 mg/day of elemental iron and intravenous iron 50-100 mg/week or 500-100 mg/month (for patients on predialysis or peritoneal dialysis) as therapeutic schedules; subcutaneous route for EPO administration at 80-120 U/kg body weight/week as starting doses. Some issues may be debatable, such as, the underestimation of dialysis efficacy among the causes of inadequate response to EPO as well as the risk of thrombosis among the possible side effects of EPO therapy, or the lack of recommendation for upper limits of FERR values. However, this exhaustive study is an important demonstration of efforts to improve the quality of care in CRF patients.

Topics: Anemia; Epoetin Alfa; Erythropoietin; Humans; Italy; Kidney Failure, Chronic; Peritoneal Dialysis; Practice Guidelines as Topic; Quality Assurance, Health Care; Recombinant Proteins; Renal Dialysis

To determine the factors that govern their response to erythropoietin (EPO), we conducted a cross-sectional study of all patients in four outpatient hemodialysis facilities in Brooklyn, NY, who had end-stage renal disease (ESRD) and human immunodeficiency virus (HIV) infection and were receiving recombinant EPO. We also compared the hematocrit and EPO requirements of these patients to those of a control group of hemodialysis patients without HIV infection. We documented known duration of HIV infection, and total CD4 count was measured once. In both groups, hematocrit was measured weekly for 5 weeks and a mean value calculated for each subject. Transferrin saturation was measured twice and a mean value calculated for each subject. Intensity of hemodialysis was assessed by measuring both percent reduction of urea and serum albumin concentration twice; mean values were calculated for each subject. Twenty-nine (88%) of 33 study subjects had acquired immunodeficiency syndrome. Mean known duration of HIV infection was 49 +/- 32.5 months (median, 48 months), and mean total CD4 count was 143 +/- 152.4 cells/mm3 (median, 72 cells/mm3). Mean hematocrit in the study subjects was 27.4% +/- 4.7% compared with 27.6% +/- 3.7% in the controls (P = 0.69). Mean thrice-weekly EPO dose was higher in the study subjects (90 +/- 52 U/kg body weight) than in the controls (62 +/- 36 U/Kg body weight) (P = 0.001). Among the study subjects, hematocrit had direct univariate correlations with serum albumin concentration (r = 0.43; P = 0.02), transferrin saturation (r = 0.4; P = 0.03), and percent reduction of urea (r = 0.4; P = 0.02), but not with total CD4 count (r = -0.05; P = 0.8) or known duration of HIV infection (r = -0.11; P = 0.55). There was an inverse correlation between hematocrit and dose of EPO (r = -0.5; P = 0.003). Multiple regression analysis showed that transferrin saturation (P = 0.01) and percent reduction of urea (P = 0.003) had direct correlations with hematocrit after adjustment for other factors. There was an inverse relationship between hematocrit and dose of EPO (P = 0.0006). We conclude that in patients with ESRD and HIV infection receiving hemodialysis, the response to EPO (hematocrit) is modulated by the dose of EPO, quantity of hemodialysis, and transferrin saturation, but not by the severity of HIV disease. Hemodialysis patients infected with HIV receive a higher dose of EPO than those without HIV infection.

Topics: Adult; CD4 Lymphocyte Count; Cross-Sectional Studies; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hematocrit; HIV Infections; Humans; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Regression Analysis; Renal Dialysis; Serum Albumin; Severity of Illness Index; Transferrin; Treatment Outcome

Topics: Anemia; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Humans; Iron; Kidney Failure, Chronic; Recombinant Proteins

Topics: Anemia; Animals; Dog Diseases; Dogs; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Kidney Failure, Chronic; Recombinant Proteins

Anemia is best managed with an effective protocol that provides standardized guidance for clinical interventions while maintaining the flexibility to respond to the needs of individual patients. An anemia management protocol can help nurses and other clinicians: (a) monitor and manage erythropoietic parameters, (b) successfully achieve the higher hematocrit (33% to 36%) and hemoglobin (11 g/dL to 12 g/dL) target levels recommended by the Dialysis Outcomes Quality Initiative (DOQI) guidelines, and (c) maintain a stable Hct to help manage the new Medicare Hematocrit Measurement Audit policy. Maintaining a stable hematocrit higher in the target range has been associated with improved patient outcomes. This article describes how to use a continuous quality improvement (CQI) approach to develop an anemia management protocol. The potential benefits of coordinating protocol implementation through an anemia management nurse are also discussed.

Topics: Anemia; Clinical Protocols; Epoetin Alfa; Erythropoietin; Hematinics; Hematocrit; Hemoglobins; Humans; Iron; Kidney Failure, Chronic; Monitoring, Physiologic; Outcome Assessment, Health Care; Recombinant Proteins

Following the successful replacement of diseased kidneys by renal homotransplants, regression of the anemia of chronic renal disease was found in five patients. Increased erythropoietic-stimulating activity was demonstrated in the serum of one patient seven weeks after renal transplantation when he suffered a severe hemorrhage. It is postulated that a renal homotransplant can produce enough erythropoietin to maintain a normal hemoglobin value and to respond to the stimulus of a sudden hemorrhage.

Topics: Anemia; Epoetin Alfa; Erythrocyte Count; Erythropoiesis; Erythropoietin; Hemoglobins; Hemorrhage; Humans; Kidney Diseases; Kidney Failure, Chronic; Kidney Transplantation; Male; Postoperative Complications; Reticulocytes; Transplantation, Homologous