Supplementary Material for: Inflammation-Driven Differential Response to Intravenous versus Oral Iron Supplementation in Hemodialysis Patients: A Post Hoc Analysis of the IHOPE Trial

Background: Anemia is common in hemodialysis patients, and iron supplementation is essential for its management. However, the impact of baseline inflammation on the efficacy of oral versus intravenous iron remains unclear.
Methods: This post hoc analysis of the IHOPE trial included 193 maintenance hemodialysis patients stratified by median baseline high-sensitivity C-reactive protein (hsCRP). Patients were randomized to receive intravenous iron sucrose (100 mg every 2 weeks) or oral polysaccharide-iron complex (150 mg twice daily) for 24 weeks. The primary outcome was hemoglobin level at 24 weeks. Secondary outcomes included hsCRP, oxidative stress markers, and iron parameters.
Results: At 24 weeks, patients with high baseline hsCRP had lower hemoglobin levels than those with low hsCRP (113.8±12.0 vs 118.0±13.5 g/L, P=0.038), despite similar baseline values. Among patients receiving intravenous iron, those with high hsCRP had significantly lower hemoglobin (112.9 vs 121.3 g/L; P=0.005) and higher hsCRP and superoxide dismutase levels, suggesting persistent inflammation and oxidative stress. In contrast, hemoglobin levels were similar between high and low hsCRP subgroups in the oral iron group (P=0.913). Iron parameters and adverse events were comparable across groups.
Conclusion: Baseline inflammation significantly modifies the response to iron supplementation in hemodialysis patients. Intravenous iron is less effective in patients with elevated hsCRP, while oral iron maintains consistent efficacy regardless of inflammatory status. These findings support an individualized iron therapy approach based on inflammatory profiling to optimize anemia management in dialysis patients.
Keywords: Hemodialysis; Anemia; Iron supplementation; Inflammation; High-sensitivity C-reactive protein; Oxidative stress