epoetin-alfa and Hypertrophy--Left-Ventricular

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

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

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

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

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

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

This randomized clinical trial is designed to assess whether the prevention and/or correction of anemia, by immediate versus delayed treatment with erythropoietin alfa in patients with chronic kidney disease, would delay left ventricular (LV) growth. Study design and sample size calculations were based on previously published Canadian data.. One hundred seventy-two patients were randomly assigned. The treatment group received therapy with erythropoietin alfa subcutaneously to maintain or achieve hemoglobin (Hgb) level targets of 12.0 to 14.0 g/dL (120 to 140 g/L). The control/delayed treatment group had Hgb levels of 9.0 +/- 0.5 g/dL (90 +/- 5 g/L) before therapy was started: target level was 9.0 to 10.5 g/dL (90 to 105 g/L). Optimal blood pressure and parathyroid hormone, calcium, and phosphate level targets were prescribed; all patients were iron replete. The primary end point is LV growth at 24 months.. One hundred fifty-two patients were eligible for the intention-to-treat analysis: mean age was 57 years, 30% were women, 38% had diabetes, and median glomerular filtration rate was 29 mL/min (0.48 mL/s; range, 12 to 55 mL/min [0.20 to 0.92 mL/s]). Blood pressure and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use were similar in the control/delayed treatment and treatment groups at baseline. Erythropoietin therapy was administered to 77 of 78 patients in the treatment group, with a median final dose of 2,000 IU/wk. Sixteen patients in the control/delayed treatment group were administered erythropoietin at a median final dose of 3,000 IU/wk. There was no statistically significant difference between groups for the primary outcome of mean change in LV mass index (LVMI) from baseline to 24 months, which was 5.21 +/- 30.3 g/m2 in the control/delayed treatment group versus 0.37 +/- 25.0 g/m2 in the treatment group. Absolute mean difference between groups was 4.85 g/m2 (95% confidence interval, -4.0 to 13.7; P = 0.28). Mean Hgb level was greater in the treatment group throughout the study and at study end was 12.75 g/dL (127.5 g/L in treatment group versus 11.46 g/dL [114.6 g/L] in control/delayed treatment group; P = 0.0001). LV growth occurred in 20.1% in the treatment group versus 31% in the control/delayed treatment group (P = 0.136). In patients with a stable Hgb level, mean LVMI did not change (-0.25 +/- 26.7 g/m2), but it increased in those with decreasing Hgb levels (19.3 +/- 28.2 g/m2; P = 0.002).. This trial describes disparity between observational and randomized controlled trial data: observed and randomly assigned Hgb level and LVMI are not linked; thus, there is strong evidence that the association between Hgb level and LVMI likely is not causal. Large randomized controlled trials with unselected patients, using morbidity and mortality as outcomes, are needed.

Topics: Adult; Aged; Anemia; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Calcium; Canada; Chronic Disease; Epoetin Alfa; Erythropoietin; Female; Heart Failure; Heart Ventricles; Hemoglobins; Humans; Hypertension; Hypertrophy, Left Ventricular; Kidney Diseases; Lipids; Male; Middle Aged; Organ Size; Parathyroid Hormone; Phosphates; Recombinant Proteins; Renal Dialysis; Single-Blind Method; Treatment Failure; Ultrasonography

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

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

Topics: Anemia; Cardiovascular Diseases; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobins; Humans; Hypertrophy, Left Ventricular; Recombinant Proteins; Renal Insufficiency, Chronic

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

Topics: Anemia; Cardiovascular Diseases; Epoetin Alfa; Erythropoietin; Heart Failure; Hemoglobins; Humans; Hypertrophy, Left Ventricular; Recombinant Proteins; Renal Insufficiency, Chronic

Topics: Anemia; Bias; Biomarkers; Chronic Disease; Epoetin Alfa; Erythropoietin; Goals; Hemoglobins; Humans; Hypertrophy, Left Ventricular; Kidney Diseases; Randomized Controlled Trials as Topic; Recombinant Proteins; Reference Values; Research Design; Treatment Outcome

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