Safety and efficacy of recombinant human erythropoietin in correcting the anemia of patients with chronic renal allograft dysfunction

Abstract

Recombinant human erythropoietin (rHuEPO) is effective in correcting anemia in hemodialysis, peritoneal dialysis, and predialysis patients. Limited studies in patients with failing renal allografts suggest a similar efficacy but provide little information concerning benefits, dose requirements, or adverse events. This study examined these considerations in a group of 40 patients (18 men; 22 women) aged 40.3 ± 13.8 yr with stable, chronic renal allograft failure. All patients had a hemoglobin <95 g/L and a serum creatinine >250 μmol/L at baseline. Patients received rHuEPO (50 U/kg sc) three times weekly for 24 wk along with iron po if serum ferritin was <100 μg/L. Mean hemoglobin rose from 78.9 ± 10.4 to 102.6 ± 18.4 g/L after 24 wk. Mean rHuEPO dose at 24 wk was 129.8 ± 81.9 U/kg per week. With oral iron supplementation only, serum ferritin fell throughout the 24 wk, whereas serum iron, transferrin saturation, and total iron-binding capacity remained stable. Quality of life was assessed by use of the general Sickness Impact Profile and the disease-specific Transplant Disease Questionnaire measures at baseline and every 8 wk during rHuEPO therapy. Significant improvement was noted in global Sickness Impact Profile scores and in four of five dimensions of the Transplant Disease Questionnaire. Serious adverse events were infrequent. No change in mean systolic or diastolic blood pressure was noted, although there was a significantly increased need for antihypertensive drugs in 18 patients (P = 0.0002). A significant inverse correlation was noted between baseline renal function and maintenance rHuEPO dose (r=-0.45; P < 0.05). Twelve patients returned to dialysis during the study. Compared with the 25 patients who completed 24 wk of rHuEPO therapy, these 12 patients had a lower hemoglobin (72.6 ± 10.6 versus 81.0 ± 9.1 g/L; P < 0.05), lower creatinine clearance (16.7 ± 12.0 versus 24.1 ± 12.4 mL/min per 1.73 m2; P < 0.05), and higher serum creatinine (539.7 ± 156.8 versus 366.1 ± 130 μmol/L; P < 0.05) at baseline. rHuEPO was effective in improving anemia in patients with failing renal allografts. Dose requirements and quality-of-life benefits were similar to those reported for other renal failure populations. The higher dose of rHuEPO required for some patients suggests that rHuEPO may be less effective as GFR falls. Further data are required to clarify the role of rHuEPO in the progression of renal failure in these patients.