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

Nephrol Dial Transplant. 2010 Dec;25(12):3996-4002. doi: 10.1093/ndt/gfq321. Epub 2010 Jun 10.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anemia, Iron-Deficiency / blood
  • Anemia, Iron-Deficiency / prevention & control*
  • Antimicrobial Cationic Peptides / blood*
  • Biomarkers / blood
  • Female
  • Hematinics / therapeutic use*
  • Hemoglobins / metabolism
  • Hepcidins
  • Homeostasis / physiology
  • Humans
  • Injections, Intravenous
  • Iron / administration & dosage
  • Iron / therapeutic use*
  • Kidney Failure, Chronic / blood*
  • Kidney Failure, Chronic / therapy*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Predictive Value of Tests
  • Renal Dialysis*
  • Retrospective Studies
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Substances

  • Antimicrobial Cationic Peptides
  • Biomarkers
  • HAMP protein, human
  • Hematinics
  • Hemoglobins
  • Hepcidins
  • Iron