Serum hepcidin-25 levels in patients with chronic kidney disease are independent of glomerular filtration rate.

BACKGROUND Hepcidin is a key regulator of iron homeostasis and levels are elevated in patients with chronic kidney disease (CKD). Hepcidin may explain the often observed imbalance in iron metabolism in patients with CKD. We evaluated the influence of estimated glomerular filtration rate (eGFR) on serum levels of hepcidin-25 and its isoforms in patients with renal dysfunction. METHODS Serum levels of the biologically active hepcidin-25 and its isoforms were determined in CKD and dialysis patients by a mass spectrometry-based assay. RESULTS In 83 patients with CKD not requiring dialysis, serum hepcidin-25 levels were not significantly increased (5.1 nM versus 4.2 nM, P = 0.30) and positively correlated with ferritin (r = 0.74, P < 0.01). Multiple regression analysis showed ferritin to be the only significant predictor of hepcidin-25 levels. Serum hepcidin-25 levels were not dependent on eGFR. In contrast, hepcidin-20 and total hepcidin levels showed an independent significant inverse correlation with eGFR. In 48 haemodialysis patients, median hepcidin-25 levels were significantly higher than in CKD patients (9.4 nM versus 5.1 nM, P < 0.001) and again strongly correlated with ferritin (r = 0.79, P < 0.001). CONCLUSIONS eGFR is not a major determinant of serum hepcidin-25 levels. In contrast, the hepcidin isoforms hepcidin-20 and hepcidin-22 accumulate in patients with renal impairment.