THE EFFECTS OF RECOMBINANT-HUMAN-ERYTHROPOIETIN ON MEAN CORPUSCULAR VOLUME IN PATIENTS WITH THE ANEMIA OF CHRONIC-RENAL-FAILURE

In historical studies erythropoietin stimulated bone marrow was shown to produce less stable, macrocytic, ''stress erythrocytes''. Recent wo rk from our lab suggests that erythropoietin serves as both a growth f actor and as a survival factor. To investigate the effects of recombin ant human erythropoietin (rHuEPO) on development of red blood cell siz e of these longer lived erythrocytes, rHuEPO in 50-150 U/kg/dose was a dministered to patients with the anemia of chronic renal failure (CRF) . Mean corpuscular volume (MCV) was determined at control, short term (n = 117, avg. 53 d), intermediate term (n = 73, avg. 136 d) and at lo ng term (n = 66, avg. 221d) for effects of rHuEPO. Statistical evaluat ion at these time points was made comparing all patients to themselves as their own controls and using contingency tables for distribution o f RBC size change. MCV at both short term (p =.02) and intermediate-te rm (p <.01) was decreased; there was no change (p =.71) at the long te rm. Analysis of distribution showed a significant (p <.01) trend towar d microcytosis at short- and intermediate terms. This decrease of MCV and trend toward microcytosis is consistent with iron deficiency secon dary to the early, rapid increase in bone marrow iron utilization and early increased reticulocytosis. Previous reports from our laboratory coupled with data presented in this report refute earlier findings tha t rHuEPO creates a ''stress'' mechanism producing less stable macrocyt es.