Responsiveness to Erythropoiesis‑Stimulating Agents and Hemoglobin Variability in Japanese Patients With End‑Stage Kidney Disease

Abstract Background Serum hemoglobin variability is a risk factor for cardiovascular mortality in end-stage kidney disease (ESKD). However, the indicators that reflect hemoglobin variability remain insufficiently investigated. We examined the association between the erythropoietin resistance index (ERI), a marker of responsiveness to erythropoiesis-stimulating agents, and hemoglobin variability in ESKD. Methods In this retrospective observational study, we enrolled 38 outpatients receiving maintenance hemodialysis, including two undergoing combined peritoneal-hemodialysis therapy. ERI at baseline and residual standard deviation of hemoglobin (Hb‑RSD) during follow‑up were evaluated. Independent determinants of ERI were identified using multiple regression analysis after adjusting for potential confounders. Results Relative to the low‑ERI group, the high‑ERI group (≥75th percentile) exhibited higher Hb-RSD. ERI was positively correlated with Hb‑RSD ( r = 0.473, p = 0.003). In multivariable regression analyses, ERI remained independently associated with Hb‑RSD after adjusting for confounding variables ( β = 0.607, p = 0.003). Furthermore, a receiver operating characteristic analysis for high Hb‑RSD (≥ 75th percentile) identified an ERI cutoff of 7.8 IU/kg·g/dL (AUC 0.729; sensitivity 70%; specificity 78%). Conclusions Among patients with ESKD, higher ERI values were associated with greater hemoglobin variability. ERI may serve as a useful surrogate marker for predicting hemoglobin fluctuations. Larger multicenter studies with longer follow-up are needed to confirm these findings.