Background: Previous epidemiological evidence has suggested that responsiveness to erythropoiesis-stimulating agents (ESAs) is related to prognosis in hemodialysis (HD) patients. We investigated the effects of hyporesponsiveness to ESA on mortality and cardiovascular events in Japanese HD patients, taking modifying factors into account. Methods: A total of 2,905 Japanese HD patients aged ≥18 years who received ESA treatment were prospectively followed up for 4 years. Responsiveness to ESA was estimated using an erythropoietin resistance index (ERI), defined as erythropoietin dosage per week divided by post-HD weight and hemoglobin value (U/kg/week/g/dl). Patients were divided into three groups by tertiles of ERI levels: low ERI, ≤5.10; intermediate ERI, 5.11–9.43; high ERI, ≥9.44. Risk estimates were calculated by a Cox proportional hazards model, adjusting for potential confounders. Results: During follow-up, 482 patients died from any causes. The 4-year survival rate decreased linearly with higher ERI levels, being 87.5, 82.9, and 72.0 % for low, intermediate, and high ERI group (p for trend <0.001). Compared with the low ERI group, the multivariate-adjusted hazard ratio (mHR) was significantly higher in the high ERI group [mHR, 1.64 (95 % confidence interval, 1.27–2.11)]. In the high ERI group, patients with Kt/V ≥ 1.57 had a significantly lower risk of death from any causes compared with those with Kt/V ≤ 1.56 [mHR, 0.73 (0.54–0.98)]. Conclusion: Our findings suggest that ESA responsiveness can be considered a significant prognostic factor in Japanese HD patients.
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