• erythropoietin;
  • mortality;
  • USRDS;
  • confounding by indication;
  • time-dependent confounding;
  • intention-to-treat analysis;
  • pharmacoepidemiology



Erythropoietin (EPO) improves measures of quality of life and reduces transfusions. Clinical trials have reported higher mortality associated with higher hemoglobin targets in varied clinical settings, making difficult the selection of erythropoiesis stimulation strategies in end-stage kidney disease. Observational studies distinguishing an effect of EPO from underlying conditions are challenging, but promise insights relevant to real-world settings.


Using data from the United States Renal Data System, we performed a retrospective cohort study of hemodialysis patients treated between 2000 and 2004. 409 364 Medicare insured patients receiving hemodialysis therapy as of January 2000 or who began dialysis after January 2000 and survived >6 months were studied. We examined the association of EPO dose in any given month with death over subsequent follow-up.


Within each hematocrit group (<30%, 30%–< 33%, 33%–< 36%, 36%–< 39% and >39%), the hazard ratios comparing the 80th percentile to the median EPO dose were 0.88 (95% CI: [0.87–0.90]), 0.94 ([0.93–0.94]), 0.98 ([0.98–0.99]), 1.06 ([1.05–1.06]) and 1.08 ([1.07–1.09]), respectively. Within the highest hematocrit group, the association of a high EPO dose with elevated mortality was attenuated over time. Among patients with malignancy or indications of EPO resistance, the association of higher EPO dose with lower mortality was attenuated when hematocrit was low, while its association with higher mortality was stronger when hematocrit was high.


These analyses demonstrate a complex relationship between EPO dosing and mortality, suggesting a possible beneficial effect among severely anemic hemodialysis patients, but possible harm when administered to individuals with higher hematocrit levels. Copyright © 2013 John Wiley & Sons, Ltd.