title: RBC improved survival due to recombinant human erythropoietin explains effectiveness of less frequent, low dose subcutaneous therapy.
abstract: 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)
authors.affiliation: Department of Medicine, Hahnemann University, Philadelphia, Pennsylvania 19102-1192.
authors.forename: A B
authors.initials: AB
authors.lastname: Schwartz
authors.forename: S B
authors.initials: SB
authors.lastname: Kahn
authors.forename: B
authors.initials: B
authors.lastname: Kelch
authors.forename: K E
authors.initials: KE
authors.lastname: Kim
authors.forename: E
authors.initials: E
authors.lastname: Pequignot
mesh_terms: 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
chemical_list: D004921:Erythropoietin; D003404:Creatinine