E-Mail karger@karger.com Blood Purif 2013;36:29–36 DOI: 10.1159/000350583 Higher Doses of Erythropoietin-Stimulating Agents and Hyporesponsiveness to Their Effects Are Associated with Increased Mortality among Prevalent Hemodialysis Patients Angie Nishio a Bed P. Chhatkuli a Jennie Z. Ma b Kambiz Kalantari a a Division of Nephrology and b Department of Public Health Science, University of Virginia Health System, Charlottesville, Va., USA ity was 35.8%. Compared to those in the lowest tertile of ESA hyporesponsiveness, patients in the middle and upper ter- tiles had significantly higher mortality (hazard ratio, HR: 1.64, 95% CI: 1.14–2.37, and HR: 2.08, 95% CI: 1.46–2.97, respec- tively). In the Cox proportional hazard model each unit incre- ment in the ESA resistance index was associated with an HR of 2.27 (95% CI: 1.60–3.23) for mortality. In this model each 1-unit increment in ESA dose/kg or each 100-μg increment in absolute darbepoetin alfa dose were associated with a 9% increased risk of mortality (HR: 1.09, 95% CI: 1.04–1.13, and HR: 1.09, 95% CI: 1.03–1.15, respectively). Conclusions: Among prevalent hemodialysis patients, a higher degree of resistance to and higher doses of ESA are associated with increased mortality. Copyright © 2013 S. Karger AG, Basel Introduction Anemia is a common complication of chronic kidney disease (CKD). Many factors contribute to the devel- opment of anemia, including nutritional deficiencies, chronic inflammatory state, iron deficiency and ongoing blood loss associated with the hemodialysis procedure [1]. However, the most important pathogenic factor is the Key Words Erythropoietin · Anemia · End-stage renal disease · Mortality · Hyporesponsiveness · Darbepoetin alfa Abstract Background: Attempts to achieve near-normal hemoglobin levels have been associated with higher mortality among chronic kidney disease patients. Evidence suggests a higher mortality rate for those with resistance to erythropoietin- stimulating agents (ESA). We investigated the association between responsiveness to ESA, dose of ESA and mortality in our hemodialysis population. Methods: A retrospective cohort study of chronic hemodialysis patients receiving di- alysis was conducted at the University of Virginia facilities. We collected data on patient demographics, comorbidities, dialysis vintage, vascular access type, body weight, ESA dose and hemoglobin, as well as data on known risk factors for ESA hyporesponsiveness. Vital status was determined 30 months later. The association between ESA responsiveness and mortality was investigated by using the Cox proportion- al hazard model adjusting for demographics, comorbidities, access type, dialysis adequacy, serum albumin, serum para- thyroid hormone and ferritin concentrations. Results: A total of 606 patients were included. The overall 30-month mortal- Published online: May 25, 2013 Kambiz Kalantari, MD, MS Associate Professor of Medicine, Division of Nephrology University of Virginia Health System, Box 800133 Charlottesville, VA 22908 (USA) E-Mail kk6c  @  virginia.edu © 2013 S. Karger AG, Basel 0253–5068/13/0361–0029$38.00/0 www.karger.com/bpu