Recombinant Human Erythropoietin in Anemic Patients with End-stage Renal Disease. Results of a Phase III Multicenter Clinical Trial

Study Objective: To determine the effectiveness and safety of recombinant human erythropoietin (rHuEpo).

Patients: Hemodialysis patients (333) with uncomplicated anemia (hematocrit less than 0.30). All received rHuEpo intravenously, three times per week at 300 or 150 U/kg body weight, which was then reduced to 75 U/kg and adjusted to maintain the hematocrit at 0.35 +/- 0.03 (SD).

Results: The baseline hematocrit (0.223 +/- 0.002) increased to 0.35, more than 0.06 over baseline within 12 weeks in 97.4% of patients. Erythrocyte transfusions (1030 within the 6 months before rHuEpo therapy) were eliminated in all patients within 2 months of therapy. Sixty-eight patients with iron overload had a 39% reduction in serum ferritin levels after 6 months of therapy. The median maintenance dose of rHuEpo was 75 U/kg, three times per week (range, 12.5 to 525 U/kg). Nonresponders had complicating causes for anemia, myelofibrosis, osteitis fibrosa, osteomyelitis, and acute or chronic blood loss. Adverse effects included myalgias, 5%; iron deficiency, 43%; increased blood pressure, 35%; and seizures, 5.4%. The creatinine, potassium, and phosphate levels increased slightly but significantly. The platelet count increased slightly but there was no increase in clotting of vascular accesses.

Conclusions: The anemia of hemodialysis patients is corrected by rHuEpo resulting in the elimination of transfusions, reduction in iron overload, and improved quality of life. Iron stores and blood pressure must be monitored and treated to maintain the effectiveness of rHuEpo and to minimize the threat of hypertensive encephalopathy.