Context-Dependent Prognostic Significance of Total Iron-Binding Capacity by Nutritional and Inflammatory Status in Hemodialysis

Introduction: Total iron-binding capacity (TIBC) is widely used in anemia management among dialysis patients. While low TIBC reflects malnutrition and inflammation, elevated TIBC indicates iron deficiency and has been linked to adverse outcomes, including thrombotic events. We examined the prognostic value of TIBC in hemodialysis (HD) patients. Methods: We analyzed data from Phases 4–7 of the Japanese Dialysis Outcomes and Practice Patterns Study (J-DOPPS). Patients were categorized into TIBC quintiles and stratified by serum albumin (<3.8 vs ≥3.8 g/dL) or C-reactive protein (CRP; <0.1 vs ≥0.1 mg/dL). Outcomes included all-cause mortality, cardiovascular events, and thrombotic events. Cox models estimated hazard ratios (HRs), and nonlinear associations were assessed using multivariable fractional polynomials. Results: Among 5604 HD patients, 622 deaths occurred during a median follow-up of 2.0 years. In crude analyses, mortality decreased across increasing TIBC quintiles only in patients with high CRP or low albumin, but not in those with low CRP or high albumin. After multivariable adjustment, mortality risk was elevated in the highest TIBC quintile, particularly in patients with high CRP (aHR 1.89, 95% CI 1.21–2.97) and low albumin (aHR 1.29, 95% CI 0.87–1.92), whereas no significant increase was observed in those with low CRP or high albumin. Fractional polynomial models showed increased mortality risk at very high TIBC levels, limited to patients with hypoalbuminemia or inflammation. Similar patterns were observed for cardiovascular and thrombotic events. Conclusion: Elevated TIBC was associated with poor outcomes in HD patients with malnutrition or inflammation, underscoring its context-dependent prognostic value.