title: The effect of altitude on dosing and response to erythropoietin in ESRD.
abstract: For poorly understood reasons, patients with end-stage renal disease (ESRD) differ substantially in their response to treatment with recombinant erythropoietin (EPO). Because hypoxia influences many of the biologic pathways involved in erythropoiesis, the altitude at which a patient lives may affect the dose-response relationship of EPO. In this retrospective cohort study, clinical data from 341,737 incident hemodialysis patients registered in the U.S. Renal Data System were combined with elevation data from the U.S. Geological Survey to address this question. Higher altitude was associated with smaller EPO doses and higher hematocrit levels. For example, compared with patients at sea level, patients living above 6000 ft received 19% less EPO (12.9 versus 15.9 thousand units/wk) but had hematocrit levels 1.1 points higher (35.7% versus 34.6%). These associations were found within subgroups defined by sex, race, age, calendar time, cause of ESRD, and dialysis center profit status, and persisted after adjustment for various potential confounding factors. Furthermore, resistance to EPO decreased with elevation. Our results suggest that ESRD patients living at high altitude either increase endogenous EPO production or respond better to endogenous and exogenous EPO.
authors.affiliation: Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital/Harvard Medical School, 1620 Tremont Street, Suite 3030, Boston, MA 02120, USA. abrookhart@rics.bwh.harvard.edu
authors.forename: M Alan
authors.initials: MA
authors.lastname: Brookhart
authors.forename: Sebastian
authors.initials: S
authors.lastname: Schneeweiss
authors.forename: Jerry
authors.initials: J
authors.lastname: Avorn
authors.forename: Brian D
authors.initials: BD
authors.lastname: Bradbury
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Rothman
authors.forename: Michael
authors.initials: M
authors.lastname: Fischer
authors.forename: Jyotsna
authors.initials: J
authors.lastname: Mehta
authors.forename: Wolfgang C
authors.initials: WC
authors.lastname: Winkelmayer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000531:Altitude; D000740:Anemia / Q000188:drug therapy* / Q000209:etiology; D004921:Erythropoietin / Q000008:administration & dosage*; D005260:Female; D006400:Hematocrit; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D004921:Erythropoietin