title: One year of rHuEPO therapy prolongs RBC survival and may stabilize RBC membranes despite natural progression of chronic renal failure to uremia and need for dialysis.
abstract: rHuEPO was administered to eight patients with chronic renal failure (CRF) and uremia (U) for 1 year. Creatinine Clearance (GFR) averaged 14.3 (9-25) ml/min at an Hct of 28% (26-30). Baseline RBC survival by 51Cr T1/2 was highly correlated with GFR (r = 0.66), p less than 0.05 (2), average 21.6 days. Repeat 51Cr T1/2 at 3 months with GFR 10 ml/min at Hct 38% was prolonged by 7 days to 28.6 (p less than 0.005), and at 1 year remained increased to 28 days (p less than 0.001) with Hct 39%, despite further decreased GFR to less than 4 ml/min and need for dialysis. Reticulocytes varied from 1.6% to 7.4 (3-6 weeks) to 3.1 (3 months) and 1.5% (1 year). Bone marrow cellularity increased from 36% to 47% (3 months) and 44% (1 year). M:E ratio decreased from 3.9:1 to 1.7:1 (3 months) to 1.6:1 (1 year). Marrow iron decreased from 4.1/6 to 2.4/6 (3 months) to 1.8/6 (1 year). Doses of rHuEPO had to be reduced to avoid polycythemia. rHuEPO stimulates erythropoiesis in pts with progressive CRF and U for 1 year. The initial increase in hematocrit is due to the early peak of reticulocytes. At 3 months, rHuEPO maintains the increased hematocrit by three mechanisms: 1) increased reticulocytosis, 2) a trend to increased bone marrow erythroid cellularity, and 3) lengthened RBC survival. At 1 year of rHuEPO therapy, the trend to increased marrow cellularity persists, however, the maintenance of target hematocrit is via a lengthened RBC survival. Despite progression of CRF and U, rHuEPO produced RBCs with longer survival than expected. RBC membranes may have been stabilized by rHuEPO.
authors: Department of Medicine, Hahnemann University School of Medicine, Philadelphia, Pennsylvania.
authors: A B
authors: AB
authors: Schwartz
authors: B
authors: B
authors: Kelch
authors: L
authors: L
authors: Terzian
authors: J
authors: J
authors: Prior
authors: K E
authors: KE
authors: Kim
authors: E
authors: E
authors: Pequinot
authors: S B
authors: SB
authors: Kahn
mesh_terms: D000328:Adult; D000368:Aged; D001810:Blood Volume / Q000187:drug effects; D001853:Bone Marrow / Q000187:drug effects; D004311:Double-Blind Method; D004905:Erythrocyte Aging / Q000187:drug effects*; D004910:Erythrocyte Membrane / Q000187:drug effects*; D004921:Erythropoietin / Q000008:administration & dosage*; D005260:Female; D005500:Follow-Up Studies; D006400:Hematocrit; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage; D006435:Renal Dialysis; D012156:Reticulocytes / Q000187:drug effects; D014511:Uremia / Q000097:blood*
chemical_list: D011994:Recombinant Proteins; D004921:Erythropoietin