Neocytolysis Contributes to the Anemia of Renal Disease

Neocytolysis is a recently described physiologic process effecting selective hemolysis of young red blood cells in circumstances of plethora. Erythropoietin depression appears to initiate the process, providing rationale to investigate its contributions to the anemia of renal disease. When erythropoietin therapy was withheld, four of five stable hemodialysis patients demonstrated Cr-51 red cell survival patterns indicative of neocytolysis; red cell survival was short in the first 9 days, then normalized. Two of these patients received oral (13)C-glycine and (15)N-glycine and showed pathologic enrichment of stool porphyrins by the most recently ingested isotope when EPO therapy was held. This confirms selective hemolysis of newly-released red cells. (One patient had chronic hemolysis by isotope studies of blood and stool.) Thus, neocytolysis can contribute to the anemia of renal disease and explains some unresolved issues about such anemia. One implication is the prediction that intravenous bolus erythropoietin therapy is metabolically and economically inefficient compared to lower doses given more frequently subcutaneously.