title: The role of hepcidin-25 in kidney transplantation.
abstract: BACKGROUND
  Hepcidin-25 is a peptide hormone involved in iron absorption and homeostasis and found at increased serum levels in conditions involving systemic inflammation, renal dysfunction, and increased adiposity. Hepcidin may play a role in the pathogenesis of anemia, but its role in kidney transplantation is undefined.
  
  
  METHODS
  This study enrolled 100 stable patients beyond 12 months after transplantation, from a large single United Kingdom center. Serum hepcidin-25 level, and relevant demographic and laboratory data pertinent to posttransplantation anemia, were measured and collected. Independent predictors of serum hepcidin were evaluated, and the relationship between hepcidin and hemoglobin, assessed.
  
  
  RESULTS
  Independent associations were seen between higher hepcidin levels and allograft dysfunction (estimated glomerular filtration rate), increased inflammation (high-sensitivity C-reactive peptide), higher transferrin saturation (a marker of iron stores), and the use of marrow-suppressive medication (P<0.05 for all). Higher fat tissue index (whole-body multifrequency bioimpedance measurement) was also associated with higher hepcidin levels, but this relationship did not persist after adjustment for inflammation (high-sensitivity C-reactive peptide). In turn, inflammation was associated with increased fat tissue index (P=0.01) and male gender (P=0.04). A nonlinear association between serum hepcidin level and hemoglobin was seen, with a progressive fall in hemoglobin as hepcidin levels rose to 100 ng/mL, but little effect thereafter (P=0.009). This association was independent of renal dysfunction and female gender, both of which were also independently associated with a lower hemoglobin level.
  
  
  CONCLUSIONS
  These results highlight possible mechanisms of hemoglobin reduction in kidney transplantation patients, and the therapeutic opportunities from understanding the role of hepcidin in this context.
authors.affiliation: Department of Nephrology and Kidney Transplantation, Queen Elizabeth Hospital Birmingham, Birmingham, UK.
authors.forename: Winnie
authors.initials: W
authors.lastname: Chan
authors.forename: Douglas
authors.initials: D
authors.lastname: G Ward
authors.forename: Andrew
authors.initials: A
authors.lastname: McClean
authors.forename: Jos
authors.initials: J
authors.lastname: A Bosch
authors.forename: David
authors.initials: D
authors.lastname: Jones
authors.forename: Okdeep
authors.initials: O
authors.lastname: Kaur
authors.forename: Mark
authors.initials: M
authors.lastname: Drayson
authors.forename: Alison
authors.initials: A
authors.lastname: Whitelegg
authors.forename: Tariq
authors.initials: T
authors.lastname: Iqbal
authors.forename: Philip G
authors.initials: PG
authors.lastname: McTernan
authors.forename: Chris
authors.initials: C
authors.lastname: Tselepis
authors.forename: Richard
authors.initials: R
authors.lastname: Borrows
mesh_terms: D050154:Adiposity / Q000502:physiology; D000328:Adult; D023181:Antimicrobial Cationic Peptides / Q000097:blood / Q000502:physiology*; D002097:C-Reactive Protein / Q000378:metabolism; D015331:Cohort Studies; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology; D006454:Hemoglobins / Q000378:metabolism*; D064451:Hepcidins; D006801:Humans; D007668:Kidney / Q000502:physiology*; D016030:Kidney Transplantation / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012189:Retrospective Studies; D012737:Sex Factors; D006113:United Kingdom
chemical_list: D023181:Antimicrobial Cationic Peptides; D006454:Hemoglobins; D064451:Hepcidins; C545475:hepcidin 25, human; D002097:C-Reactive Protein