RBC improved survival due to recombinant human erythropoietin explains effectiveness of less frequent, low dose subcutaneous therapy.
Effectiveness of less frequent, once weekly, low dose subcutaneous recombinant human erythropoietin (rHuEPO) in maintaining 35% hematocrit in patients with chronic renal failure, predialysis and ESRD receiving dialysis, is dependent on rHuEPO induced prolonged RBC survival. One year of weekly rHuEPO doses to 7 patients originally part of the National Cooperative Protocol were evaluated for a total of 372 weeks for an average of 53 weeks per patient. The original 8 to 12 week dosage was directed by protocol for units per dose at 3 doses per week (4 IV, 3 subcutaneous). Thereafter, all doses were subcutaneous. Units/dose and doses/week were titrated to keep hematocrit at 35-38%. Dosage reduction of rHuEPO was determined by two investigators at the time of each examination. Statistical correlation was performed on effect of rHuEPO on 51Cr T1/2 RBC survival changes and changes of rHuEPO weekly doses. Patients evaluated at specific time points in the study were compared to themselves as their own controls by paired t-test analysis. The long-term increased RBC count correlated with prolonged RBC survival by 51Cr T1/2 rather than reticulocytosis. A relatively increased ease of sustaining the target hematocrit of 35% was demonstrated from the 8th week to 1 year. Thirty-two percent of the expanded RBC mass was older at 12 weeks and 22% was older at 1 year. rHuEPO dosage was reduced to 27% at weeks 8-12, to 21% at weeks 20-24, and to 38% at 1 year corresponding to prolonged RBC survival. 51Cr T1/2 increased from 21.6 days control to 28.6 days at 12 weeks and 26.3 days at 1 year.(ABSTRACT TRUNCATED AT 250 WORDS)
Schwartz
A B
AB
Department of Medicine, Hahnemann University, Philadelphia, Pennsylvania 19102-1192.
Kahn
S B
SB
Kelch
B
B
Kim
K E
KE
Pequignot
E
E
D000328:Adult; D000368:Aged; D002470:Cell Survival / Q000187:drug effects*; D003404:Creatinine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004912:Erythrocytes / Q000187:drug effects*; D004921:Erythropoietin / Q000008:administration & dosage*; D005919:Glomerular Filtration Rate; D006400:Hematocrit; D006801:Humans; D007279:Injections, Subcutaneous; D007676:Kidney Failure, Chronic / Q000628:therapy*; D008875:Middle Aged; D006435:Renal Dialysis
D004921:Erythropoietin; D003404:Creatinine