Recombinant human erythropoietin: physiology, pathophysiology of anemia in renal failure, and economic aspects related to dosing.

The anemia associated with renal failure has been studied for over 150 years. It results primarily from inadequate production of erythropoietin such that plasma levels in dialysis patients are only 25% of those expected for the degree of anemia. Shortened red call survival, iron and other nutritional deficiencies, and uremic inhibitors have a secondary and minor role. Recombinant human erythropoietin (rHuEPO) is now used to treat this anemia. It is heavily sialated, which permits its circulation long enough to act on the bone marrow where, in concert with other growth factors, it commits progenitor cells to the erythroid cell pathway. Major issues related to clinical use of rHuEPO are dosage, resistance, and cost. Pharmacokinetic studies predict significant weekly dose reductions (and therefore cost savings) using the subcutaneous route compared to the intravenous route permitting more patients to be treated optimally. Biological heterogeneity and not hyperparathyroidism or aluminum overload accounts for most instances in which more than 450 U/kg/wk of rHuEPO is required.