HFE mutations modulate the effect of iron on serum hepcidin-25 in chronic hemodialysis patients

Luca Valenti, Domenico Girelli, Giovanni Francesco Valenti, Annalisa Castagna, Giovanna Como, Natascia Campostrini, Raffaela Rametta, Paola Dongiovanni, Piergiorgio Messa, Silvia Fargion

Research output: Contribution to journalArticlepeer-review


Background and objectives: Increased serum hepcidin has been reported in patients receiving chronic hemodialysis, and hypothesized to contribute to the alterations of iron metabolism of end-stage renal disease. However, no quantitative assessment is available to date; the clinical determinants are still under definition; and the role of genetic factors, namely HFE mutations, has not yet been evaluated. The aim of this study was to quantitatively assess serum hepcidin-25 in hemodialysis patients versus controls, and analyze the relationship between hepcidin, iron indices, HFE genotype, and erythropoietic parameters. Design, setting, participants & measurements: Sixty-five hemodialysis patients and 57 healthy controls were considered. Hepcidin-25 was evaluated by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry, HFE genotype by restriction analysis. Results: Serum hepcidin-25 was higher in hemodialysis patients compared with controls. In patients, hepcidin-25 correlated positively with ferritin and C reactive protein, and negatively with serum iron after adjustment for confounders. Hepcidin/ ferritin ratio was lower in patients with (n = 25) than in those without (n = 40) HFE mutations. At multivariate analysis, hepcidin-25 was independently associated with ferritin and HFE status. In a subgroup of 22 "stable" patients, i.e., with Hb levels on target, normal CRP levels, and absence of complications for at least 1 yr, hepcidin-25 was negatively correlated with Hb levels independently of confounders. Conclusions: Serum hepcidin-25 is increased in hemodialysis patients, regulated by iron stores and inflammation, and relatively reduced in subjects carrying frequent HFE mutations. Hepcidin-25 may contribute to the pathogenesis of anemia by decreasing iron availability.

Original languageEnglish
Pages (from-to)1331-1337
Number of pages7
JournalClinical Journal of the American Society of Nephrology
Issue number8
Publication statusPublished - 2009

ASJC Scopus subject areas

  • Nephrology
  • Transplantation
  • Epidemiology
  • Critical Care and Intensive Care Medicine
  • Medicine(all)


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