Longitudinal assessments of erythropoietin-stimulating agent responsiveness and the association with specific clinical outcomes in dialysis patients.
BACKGROUND
Dose requirements of erythropoietin-stimulating agents (ESAs) can vary considerably over time and may be associated with cardiovascular outcomes. We aimed to longitudinally assess ESA responsiveness over time and to investigate its association with specific clinical end points in a time-dependent approach.


METHODS
The German Diabetes and Dialysis study (4D study) included 1,255 diabetic dialysis patients, of whom 1,161 were receiving ESA treatment. In those patients, the erythropoietin resistance index (ERI) was assessed every 6 months during a median follow-up of 4 years. The association between the ERI and cardiovascular end points was analyzed by time-dependent Cox regression analyses with repeated ERI measures.


RESULTS
Patients had a mean age of 66 ± 8.2 years; 53% were male. During follow-up, a total of 495 patients died, of whom 136 died of sudden death and 102 of infectious death. The adjusted and time-dependent risk for sudden death was increased by 19% per 5-unit increase in the ERI (hazard ratio, HR = 1.19, 95% confidence interval, CI = 1.07-1.33). Similarly, mortality increased by 25% (HR = 1.25, 95% CI = 1.18-1.32) and infectious death increased by 27% (HR = 1.27, 95% CI = 1.13-1.42). Further analysis revealed that lower 25-hydroxyvitamin D levels were associated with lower ESA responsiveness (p = 0.046).


CONCLUSIONS
In diabetic dialysis patients, we observed that time-varying erythropoietin resistance is associated with sudden death, infectious complications and all-cause mortality. Low 25-hydroxyvitamin D levels may contribute to a lower ESA responsiveness.
Division of Nephrology, Department of Medicine, University Hospital Würzburg, Würzburg, Germany.
Andreas
A
Schneider
Lena
L
Gutjahr-Lengsfeld
Eberhard
E
Ritz
Hubert
H
Scharnagl
Götz
G
Gelbrich
Stefan
S
Pilz
Iain C
IC
Macdougall
Christoph
C
Wanner
Christiane
C
Drechsler
D000368:Aged; D004351:Drug Resistance; D005260:Female; D006397:Hematinics / Q000627:therapeutic use*; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D006435:Renal Dialysis; D016896:Treatment Outcome
D006397:Hematinics; D006454:Hemoglobins