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.


CONCLUSIONS
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.
Kaysen
George A
GA
Division of Nephrology, Department of Medicine, University of California Davis, Department of Veterans Affairs, Medical Northern California Health Care System, CA, USA. gakaysen@ucdavis.edu
Müller
Hans G
HG
Ding
Jimin
J
Chertow
Glenn M
GM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000188:drug therapy / Q000209:etiology / Q000401:mortality; D015415:Biomarkers; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004351:Drug Resistance; D004921:Erythropoietin / Q000008:administration & dosage* / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006400:Hematocrit; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000175:diagnosis; D007501:Iron / Q000627:therapeutic use; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications / Q000401:mortality / Q000628:therapy; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011994:Recombinant Proteins; D006435:Renal Dialysis / Q000009:adverse effects; D015203:Reproducibility of Results; D016019:Survival Analysis; D013997:Time Factors; D014481:United States / Q000453:epidemiology
D015415:Biomarkers; D011994:Recombinant Proteins; D004921:Erythropoietin; D007501:Iron