Associations between iron indices and erythropoiesis resistance index in maintenance hemodialysis

Abstract Background Anemia management in patients receiving maintenance hemodialysis commonly involves erythropoiesis-stimulating agents (ESAs) and intravenous (IV) iron supplementation. However, the relationships among iron administration, iron indices, and erythropoiesis resistance index (ERI) remain complex in routine clinical practice. In particular, it remains unclear whether regular low-dose IV iron administration is consistently associated with lower ERI when evaluated using longitudinal data. Methods We conducted a single-center retrospective longitudinal observational study in maintenance hemodialysis patients with at least 12 months of monthly data. Patient-month–level observations included hemoglobin, ESA dose, IV iron dose, transferrin saturation (TSAT), ferritin, albumin, C-reactive protein (CRP), and clinical stress indicators. ERI was used as a continuous outcome variable in this study. To examine temporal relationships, prior-month IV iron exposure was evaluated in relation to contemporaneous ERI. Linear mixed-effects models with patient-level random intercepts were used to account for repeated measurements. Results A total of 57 patients contributed 684 patient-month observations. Median hemoglobin was 11.1 g/dL (IQR 10.2–11.9), and median ERI was 14.0 (IQR 8.45–19.34). At comparable IV iron doses, TSAT and ferritin showed substantial variability across patient-months. In mixed-effects analyses, prior-month IV iron dose was not significantly associated with ERI in the primary model. In contrast, lower TSAT and lower albumin were independently associated with higher ERI, whereas ferritin was not. ERI also varied widely across patient-months despite similar levels of iron exposure. Conclusions In maintenance hemodialysis patients managed with regular low-dose IV iron supplementation, iron exposure was not consistently associated with ERI. Substantial variability in iron indices and ERI suggest heterogeneity in iron availability and factors influencing ESA response. These findings support a longitudinal, individualized approach to anemia management that integrates iron indices with ERI rather than relying on iron dosing alone.