Iron Availability, Inflammation, and ESA Responsiveness in Maintenance Hemodialysis: A Patient-Month Longitudinal Analysis

Background Anemia management in patients receiving maintenance hemodialysis relies on erythropoiesis-stimulating agents (ESAs) and intravenous (IV) iron supplementation. However, the relationship between iron administration, iron indices, and ESA responsiveness remains complex in routine clinical practice. In particular, whether regular low-dose IV iron supplementation consistently improves ESA responsiveness has not been well characterized using high-resolution longitudinal data. Methods We conducted a single-center retrospective longitudinal observational study in maintenance hemodialysis patients with at least 12 months of available 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. ESA responsiveness was assessed using the erythropoiesis resistance index (ERI). 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 maintenance hemodialysis 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 monthly 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 serum albumin were independently associated with higher ERI, indicating reduced ESA responsiveness. Conclusions In maintenance hemodialysis patients managed with regular low-dose IV iron supplementation, iron exposure did not uniformly translate into improved ESA responsiveness. Substantial variability in iron indices and ERI suggests heterogeneous iron utilization, potentially reflecting functional iron deficiency. These findings support a longitudinal, response-guided approach to anemia management that integrates iron indices with ESA responsiveness rather than relying on iron dosing alone.