Optimal Serum Hepcidin-25 Levels for the Management of Anemia and Iron Metabolism in Patients on Hemodialysis

Background: Chronic inflammation and reduced renal clearance can elevate hepcidin in patients with chronic kidney disease (CKD), impairing iron utilization and leading to functional iron deficiency and anemia. We determined the optimal hepcidin-25 range by examining its impacts on anemia and iron metabolism in hemodialysis patients, and its role in anemia progression. Methods: This prospective observational study included 43 outpatients undergoing hemodialysis at two hospitals. Over 12 months, laboratory parameters were collected every 4–5 weeks, yielding 469 data points. Key variables included hemoglobin (Hb), transferrin saturation (TSAT), total iron-binding capacity (TIBC), ferritin, and serum hepcidin-25 levels. Receiver operating characteristic (ROC) analysis was used to determine a hepcidin-25 cutoff associated with adequate anemia control (defined as Hb ≥10 g/dL) and ideal iron status (TSAT ≥20% and ferritin <100 ng/mL). Relationships between hepcidin-25, Hb levels in the following month, and changes in Hb level were analyzed to assess whether hepcidin-25 could predict anemia. Multivariate logistic regression analyses of albumin (Alb), C-reactive protein (CRP), TSAT, ferritin, and hepcidin-25 levels were performed to evaluate their ability to predict anemia progression. Results: Hepcidin-25 levels were significantly elevated in patients with anemia (Hb <10 g/dL) and negatively correlated with current Hb levels (p<0.01). Hepcidin-25 levels were positively correlated with TSAT and ferritin. The optimal hepcidin-25 range for maintaining ideal iron metabolism was 10–40 ng/mL, with a cutoff of ≤32.5 ng/mL for anemia control and iron metabolism optimization. Hepcidin-25 levels correlated more strongly with Hb levels in the following month than with those in the concurrent month. Hb levels tended to decrease when hepcidin-25 was ≥60 ng/mL. Of the five variables analyzed, hepcidin-25 had the highest odds ratio for predicting anemia progression. Conclusion: In patients undergoing hemodialysis, hepcidin-25 levels between 10 and 40 ng/mL may support optimal iron metabolism, while levels ≤32.5 ng/mL may help control anemia. Levels ≥60 ng/mL were associated with anemia progression, and overall, hepcidin-25 was the strongest predictor. These findings suggest that hepcidin-25 is a valuable marker for anemia prediction.