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.
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.
Schwartz
A B
AB
Department of Medicine, Hahnemann University School of Medicine, Philadelphia, Pennsylvania.
Kelch
B
B
Terzian
L
L
Prior
J
J
Kim
K E
KE
Pequinot
E
E
Kahn
S B
SB
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*
D011994:Recombinant Proteins; D004921:Erythropoietin