epoetin-alfa and Renal-Insufficiency

Anemia is a reduction in the oxygen-carrying capacity of red blood cells that results in a variety of symptoms, including dyspnea, headaches, light-headedness, and fatigue. Although anemia has been associated with reduced health-related quality of life (HRQoL), its treatment has not yet been consistently shown to improve HRQoL.. This systematic review of the literature was conducted to determine whether the treatment of anemia improves HRQoL domains, regardless of the type of underlying disease.. Data for this review were drawn from the clinical trial databases from 2 previous systematic literature reviews of erythropoiesis-stimulating protein treatment for renal insufficiency- and cancer-related anemia, both spanning the period January 1, 1980, through December 31, 2001. MEDLINE, Cancerlit, and Current Contents/Clinical Medicine were searched using the combined terms erythropoietin, kidney failure, neoplasms, and anemia. The reference lists of all identified articles were searched manually for additional relevant papers. The review included prospective studies that reported both HRQoL and hematocrit (Hct) in patients with cancer or renal insufficiency who received treatment for anemia with an erythropoiesis-stimulating protein. HRQoL was categorized by domain (overall, energy/fatigue, physical, activity); changes in HRQoL domains were expressed as effect sizes and meta-analyzed, as were correlation coefficients. The effects on HRQoL of dropout rate, study duration, baseline Hct, and change in Hct were examined in meta-regression analyses.. Sixteen studies each were identified in patients with renal insufficiency (N = 2253) and patients with cancer (N = 10,695). The treated groups included 11,710 patients, and the control groups included 1238 patients. The baseline Hct in all treated groups averaged 26.0%: 28.3% in the group with cancer and 24.4% in the group with renal insufficiency. The mean improvement in Hct from baseline to the end of treatment was 8.3% (range, 1.0%-16.5%) in treated patients and 1.0% (range, 0.0%-3.3%) in controls. The Hct changes were similar in treated patients with cancer and treated patients with renal insufficiency, as was the HRQoL effect size (0.43). Dropout rate and study duration were not significant predictors of HRQoL changes, but change in Hct was a significant predictor in both conditions. Meta-analysis of the correlation coefficients, adjusting for HRQoL domains, showed a consistent and significant positive correlation between change in Hct and change in HRQoL (P < 0.001).. The consistency in both direction and magnitude of effect across many studies and thousands of patients supports the hypothesis that treatment of anemia with erythropoiesis-stimulating protein improves selected HRQoL domains in patients with renal insufficiency- or cancer-related anemia.

Topics: Anemia; Clinical Trials as Topic; Epoetin Alfa; Erythropoietin; Hematocrit; Humans; Neoplasms; Quality of Life; Recombinant Proteins; Renal Insufficiency; Treatment Outcome

Trials of anemia correction in chronic kidney disease have found either no benefit or detrimental outcomes of higher targets. We did a secondary analysis of patients with chronic kidney disease enrolled in the Correction of Hemoglobin in the Outcomes in Renal Insufficiency trial to measure the potential for competing benefit and harm from achieved hemoglobin and epoetin dose trials. In the 4 month analysis, significantly more patients in the high-hemoglobin compared to the low-hemoglobin arm were unable to achieve target hemoglobin and required high-dose epoetin-alpha. In unadjusted analyses, the inability to achieve a target hemoglobin and high-dose epoetin-alpha were each significantly associated with increased risk of a primary endpoint (death, myocardial infarction, congestive heart failure or stroke). In adjusted models, high-dose epoetin-alpha was associated with a significant increased hazard of a primary endpoint but the risk associated with randomization to the high hemoglobin arm did not suggest a possible mediating effect of higher target via dose. Similar results were seen in the 9 month analysis. Our study demonstrates that patients achieving their target had better outcomes than those who did not; and among subjects who achieved their randomized target, no increased risk associated with the higher hemoglobin goal was detected. Prospective studies are needed to confirm this relationship and determine safe dosing algorithms for patients unable to achieve target hemoglobin.

Topics: Aged; Anemia; Chronic Disease; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Female; Hemoglobins; Humans; Kidney Diseases; Male; Middle Aged; Recombinant Proteins; Renal Insufficiency; Risk; Treatment Outcome

Patients with renal failure and undergoing hemo- (HD) or peritoneal dialysis are under oxidative stress which is thought to contribute to the long-term complications noted in this patient population. One effect of HD-induced oxidative stress is via red blood cell (RBC) membrane lipid peroxidation leading to RBC destruction and anemia. Interaction of this oxidative stress with epoetin (EPO) treatment to increase RBC number and Hb concentration remains unexplored.. This preliminary study used RT-PCR as well as colorimetric based assay approaches to evaluate the effect of EPO-alpha treatment on markers of oxidative stress in hemodialysis patients. Eighteen patients (12 males, 6 females, age range 45 - 68), were treated with EPO-alpha (Eprex) 50 UI/kg thrice weekly over an 8-month study period. Monocytes were isolated at baseline, then monthly thereafter, monocyte heme-oxygenase-1 (HO-1) and plasma Hb and antioxidant power (AOP) were determined.. Treatment with EPO increased Hb (9.4 +/- 0.7 g/dl to 10.9 +/- 0.5, mean +/- SD p < 0.001). In addition, both monocyte HO-1 mRNA (0.34 +/- 0.08 vs. 0.59 +/- 0.02 d.u. p < 0.001) and plasma AOP (1,379.8 +/- 175 micromol/l to 1,624 +/- 170, p < 0.04) increased. While AOP changes showed no correlation with other indices, increases in HO-1 and Hb were positively correlated using 2 different measures: delta Hb (peak Hb - baseline Hb) vs. delta HO-1 (peak HO-1 mRNA - baseline HO-1 mRNA) as well as delta Hb(5 months-baseline) vs. delta HO-1 (5 months - baseline) mRNA (r = 0.81, p < 0.001 and r = 0.76, p < 0.001; respectively). In conclusion, the increases upon EPO treatment of both HO-1 gene expression and plasma AOP as well as the significant correlation between delta Hb and delta HO-1 mRNA suggest that EPO treatment reduces oxidative stress via a combination of effects. These could potentially include effects on oxidative stress directly as well as effects on the levels and types of antioxidants present in plasma.

Topics: Adult; Aged; Antioxidants; Epoetin Alfa; Erythropoietin; Female; Hematinics; Heme Oxygenase (Decyclizing); Heme Oxygenase-1; Humans; Male; Membrane Proteins; Middle Aged; Recombinant Proteins; Renal Dialysis; Renal Insufficiency; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

Anaemia is a common complication of renal failure. It can be treated with erythropoietin (EPO) administration, red blood cell transfusion (RBCT), or a combination of both. EPO has been registered for the treatment of renal anaemia in Sweden since the beginning of the 1990s, and is the primary treatment regimen for anaemia related to renal failure. The objective of this study was to carry out a cost-effectiveness analysis from a provider perspective of a treatment strategy comprising EPO and complementary RBCT compared to the traditional treatment of RBCT alone for patients with anaemia associated with renal failure in Sweden.. Incremental costs and quality-adjusted life-years (QALYs) associated with EPO (epoietin-alpha) treatment compared to the traditional therapy of RBCT were estimated. The QALY gains were estimated using a modified version of a Markov model, which is used by the UK National Institute of Clinical Excellence in their evaluations of EPO treatment in the UK. Swedish treatment practice (i.e. EPO doses and iron supplementation), patient characteristics and unit costs were used throughout the study.. The estimated cost per QALY gained from administration of EPO to renal patients falls within the range acceptable in Sweden for both haemodialysis and peritoneal dialysis patients.. EPO administration to renal patients is much more costly in Sweden than in the UK, primarily due to the higher dosage of EPO and iron supplementation used in Sweden. However, Swedish patients reach higher haemoglobin levels, and thereby achieve higher QALY gains, compared to patients in the UK.

Topics: Anemia; Cost-Benefit Analysis; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Female; Health Care Costs; Hematinics; Humans; Male; Middle Aged; Recombinant Proteins; Renal Insufficiency; Sweden; Treatment Outcome

Topics: Anemia; Contraindications; Epoetin Alfa; Erythroblasts; Erythropoietin; Humans; Recombinant Proteins; Renal Insufficiency

Topics: Anemia; Epoetin Alfa; Erythroblasts; Erythropoietin; Humans; Recombinant Proteins; Renal Insufficiency

Topics: Blood Donors; Blood Transfusion, Autologous; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Fees, Pharmaceutical; Hematinics; HIV Infections; Hypertension, Renal; Neoplasms; Premedication; Preoperative Care; Recombinant Proteins; Renal Insufficiency

Topics: Acute Kidney Injury; Anemia; Epoetin Alfa; Erythropoietin; Humans; Renal Insufficiency