title: HFE mutations modulate the effect of iron on serum hepcidin-25 in chronic hemodialysis patients.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Center for Metabolic and Liver Diseases, Department of Internal Medicine, Universitá degli Studi di Milano,Fondazione Ospedale Maggiore Policlinico MaRE IRCCS, Via F Sforza 35, 20122 Milano, Italy. luca.valenti@unimi.it
authors.forename: Luca
authors.initials: L
authors.lastname: Valenti
authors.forename: Domenico
authors.initials: D
authors.lastname: Girelli
authors.forename: Giovanni Francesco
authors.initials: GF
authors.lastname: Valenti
authors.forename: Annalisa
authors.initials: A
authors.lastname: Castagna
authors.forename: Giovanna
authors.initials: G
authors.lastname: Como
authors.forename: Natascia
authors.initials: N
authors.lastname: Campostrini
authors.forename: Raffaela
authors.initials: R
authors.lastname: Rametta
authors.forename: Paola
authors.initials: P
authors.lastname: Dongiovanni
authors.forename: Piergiorgio
authors.initials: P
authors.lastname: Messa
authors.forename: Silvia
authors.initials: S
authors.lastname: Fargion
mesh_terms: D000328:Adult; D000368:Aged; D000740:Anemia / Q000097:blood / Q000209:etiology* / Q000235:genetics; D023181:Antimicrobial Cationic Peptides / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D004920:Erythropoiesis; D005260:Female; D005293:Ferritins / Q000097:blood; D005838:Genotype; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000235:genetics; D007501:Iron / Q000097:blood*; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications / Q000235:genetics / Q000628:therapy*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D006435:Renal Dialysis; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D055815:Young Adult
chemical_list: D023181:Antimicrobial Cationic Peptides; D015415:Biomarkers; C578702:HAMP protein, human; C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D002097:C-Reactive Protein; D005293:Ferritins; D007501:Iron