Challenging the validity of the EPO index

Background: With use of recombinant erythropoietin (EPO) and intravenous iron, the majority of hemodialysis patients can achieve target hemoglobin concentrations. EPO resistance arises as a consequence of inflammation and other processes that can adversely affect survival. We hypothesized that the EPO dose-hematocrit (EPO/Hct) ratio, also known as the EPO index, may be a surrogate for inflammation and that greater EPO/Hct ratios would be associated with decreased survival. Methods: We used proportional hazards regression models and time-varying logistic models to analyze the association between EPO index and survival in US hemodialysis patients initiating hemodialysis therapy between January 1, 1999, and December 31, 2000, and followed up for up to 3 years until December 31, 2001. Results: We found an unexpected and consistent association between greater EPO index and survival in all models. The associations of EPO/Hct ratio were most prominent at intermediate Hct values and with longer dialysis vintage. Iron administration was associated with a lower risk for death independent of Hct. Conversely, greater average prior EPO dose was associated with a greater risk for death. Conclusion: EPO resistance may be reflected better by total cumulative EPO dose than the EPO/Hct ratio. The mechanism(s) responsible for the association between a greater EPO/Hct ratio and survival remains to be established, but may be a result of nonerythrogenic effects of EPO.