Proposed therapeutic algorithm for the treatment of anemia of chronic renal failure in pre-dialysis patients with low dose once weekly subcutaneous r-HuEPO. Multicenter Study Group, Israel.

Anemia of chronic renal failure (CRF) prior to initiation of dialysis is an important cause of morbidity and requires early therapeutic intervention. The current study was designed to investigate the efficacy and tolerability of a therapeutic algorithm for anemia of CRF in pre-dialysis patients which is based on low dose once-a-week subcutaneous (s.c.) administration of recombinant human erythropoietin (r-HuEPO). Thirty-one patients participated in a prospective open-label multicenter study. At baseline, hemoglobin was 8.8+/-0.1 g/dl, transferrin saturation 27+/-2%, ferritin 207+/-28 ng/ml and serum creatinine 4.7+/-0.2 mg/dl. Treatment with r-HuEPO was started at a fixed s.c. dose of 4,000 units once weekly, irrespective of body weight, and titrated upwards or downwards according to a predetermined algorithm. Hemoglobin rose to levels >10 g/dl within 8 weeks and remained stable throughout the remaining period of the study. By week 24, most patients required <or =4,000 units/week as maintenance dose. Transferrin saturation and ferritin concentration tended to fall during the course of r-HuEPO treatment, despite iron supplementation. There was no change in white blood cell or platelet count. Eight patients required an increase in antihypertensive therapy, but blood pressure remained well-controlled. Twelve patients failed to complete the full length of the study, 7 of them because dialysis had to be initiated. The rate of decline in kidney function, however, was not altered by r-HuEPO. We conclude that the proposed therapeutic algorithm is practical, efficacious, safe, and cost-effective.