Hepcidin is not useful as a biomarker for iron needs in haemodialysis patients on maintenance erythropoiesis-stimulating agents

Abstract

Background. It has been suggested that hepcidin may be useful as a tool for managing iron therapy in haemodialysis (HD) patients on erythropoiesis- stimulating agents (ESA).Methods. We used SELDI-TOF mass spectrometry assay to measure serum hepcidin-25 (Hep-25) and hepcidin-20 (Hep-20) in 56 adult HD patients on maintenance ESA to assess their ability to predict haemoglobin (Hb) response after 1 g intravenous iron (62.5 mg ferric gluconate at 16 consecutive dialysis sessions) and their relationship with markers of iron status, inflammation and erythropoietic activity.Results. At multivariate analysis (in a model that also included Hb, reticulocyte, ESA dose, HFE genotype, soluble transferrin receptor [sTfR] and C-reactive protein), Hep-25 independently correlated with ferritin (β = 0.03, P = 0.01) and the percentage of hypochromic red blood cells [%Hypo] (β = 1.84, P = 0.01), suggesting that Hep-25 may be a useful biomarker for iron stores and bone marrow iron availability. Hep-20 correlated independently with Hep-25 (β = 0.159, P <0.001) and ferritin (β = 0.006, P = 0.05), suggesting that it may be a useful additional biomarker for iron stores. On receiver operating characteristics curve analysis, neither Hep-25 nor Hep-20 significantly predicted who will increase their Hb after iron loading (AUC = 0.52 ± 0.09 and 0.54 ± 0.08, P = 0.612), and the same applied to ferritin and transferrin saturation (AUC = 0.55 ± 0.08 and 0.59 ± 0.08, P = 0.250), whereas %Hypo and reticulocyte Hb content were significant predictors (AUC = 0.84 ± 0.05 and 0.70 ± 0.08, P <0.01). At multivariate logistic regression analysis, %Hypo was the only biomarker independently associated with iron responsiveness.Conclusions. Although our study suggests an important role for hepcidin in regulating iron homeostasis in HD patients on ESA, our findings do not support its utility as a predictor of iron needs, offering no advantage over established markers of iron status. © 2010 The Author. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.