Received November 9, 2007
Accepted on January 11, 2008

CLINICAL EPIDEMIOLOGY

The Effect of Altitude on Dosing and Response to Erythropoietin in ESRD

M. Alan Brookhart ^*1, Sebastian Schneeweiss ^*, Jerry Avorn ^*, Brian D. Bradbury , Kenneth J. Rothman ^*, Michael Fischer ^*, Jyotsna Mehta ^*, and Wolfgang C. Winkelmayer ^*

*Division of Pharmacoepidemiology and Pharmacoeconomics and Renal Division, Department of Medicine, Brigham and Women’s Hospital & Harvard Medical School, Boston, Massachusetts; Department of Epidemiology, Amgen, Inc, Thousand Oaks, California; and RTI Health Solutions, Research Triangle Park, North Carolina

¹ To whom correspondence should be addressed. E-mail: abrookhart{at}rics.bwh.harvard.edu.

	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.