Hepcidin-25 Concentrations Are Markedly Increased in Patients With Chronic Kidney Disease and Are Inversely Correlated With Estimated Glomerular Filtration Rates

BACKGROUND: Hepcidin-25 regulates iron homeostasis by binding the iron transporter ferroportin, causing its degradation. Increased hepcidin-25 causes decreased intestinal iron absorption and release from intracellular stores. Our objective in this study was to measure hepcidin-25 levels in patients with chronic kidney disease (CKD) to determine if they might contribute to the anemia of CKD. METHODS: We used a hepcidin-25-specific enzyme-linked immunosorbent assay to measure hepcidin-25 in 103 CKD patients and 100 healthy individuals. We assessed in CKD subjects the correlation of hepcidin-25 with creatinine, estimated glomerular filtration rate (eGFR), hemoglobin, blood urea nitrogen, serum iron, transferrin, and ferritin. RESULTS: Hepcidin-25 concentrations in CKD patients were significantly increased compared to healthy subjects (60.4 ± 6.1 μg/l vs. 3.0 ± 0.5 μg/l, P < 0.001). Hepcidin-25 concentrations were directly correlated with creatinine (R = 0.28, P = 0.004) and inversely correlated with eGFR (R = -0.32, P = 0.001). Hepcidin-25 levels were also correlated with transferrin (R = -0.28, P = 0.004) and ferritin (R = 0.80, P < 0.001). CONCLUSION: The direct correlation of hepcidin-25 with creatinine and its inverse correlation with eGFR suggest that hepcidin-25 levels increase as renal function deteriorates, possibly due to decreased hepcidin-25 renal clearance.