title: Hepcidin and disordered mineral metabolism in chronic kidney disease.
abstract: BACKGROUND
  Hepcidin regulates iron homeostasis by blocking iron absorption from the gut and iron release from macrophage and hepatocyte stores. Hepcidin levels are elevated in kidney failure and thus, are thought to contribute to dysregulation of iron homeostasis in chronic kidney disease (CKD). However, the primary factors associated with increased hepcidin levels in CKD patients have not been well-defined. In particular, few studies examined the relationships between hepcidin and disorders of mineral metabolism, which are among the earliest and most common complications of CKD.
  
  
  METHODS
  We examined the associations between hepcidin, iron indexes, and markers of mineral metabolism in 125 patients from across the spectrum of pre-dialysis CKD. Bioactive hepcidin levels were measured in serum samples by competitive ELISA.
  
  
  RESULTS
  Hepcidin was inversely associated with eGFR and linearly associated with ferritin (p < 0.001 for both). In unadjusted analyses, increased serum phosphate and parathyroid hormone (PTH) and decreased 1,25-dihydroxyvitamin D (1,25(OH)2D) levels were associated with increased hepcidin. When examined in forward stepwise regression analysis, higher phosphate and PTH levels and lower 1,25(OH)2D and FGF23 levels were selected as independent predictors of higher hepcidin levels, whereas there was no association between eGFR and hepcidin.
  
  
  CONCLUSIONS
  Abnormalities in phosphate and vitamin D metabolism were associated with increased hepcidin levels independently of eGFR in CKD patients. These findings suggest that disorders of mineral metabolism may promote increased hepcidin secretion in CKD. Whether inflammation mediates these associations requires further study.
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine, University of Miami, Miller School of Medicine, Miami, FL, USA.
authors.forename: C
authors.initials: C
authors.lastname: Carvalho
authors.forename: T
authors.initials: T
authors.lastname: Isakova
authors.forename: G
authors.initials: G
authors.lastname: Collerone
authors.forename: G
authors.initials: G
authors.lastname: Olbina
authors.forename: M
authors.initials: M
authors.lastname: Wolf
authors.forename: M
authors.initials: M
authors.lastname: Westerman
authors.forename: O M
authors.initials: OM
authors.lastname: Gutiérrez
mesh_terms: D000900:Anti-Bacterial Agents / Q000097:blood*; D023181:Antimicrobial Cationic Peptides / Q000097:blood*; D003430:Cross-Sectional Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005919:Glomerular Filtration Rate; D064451:Hepcidins; D006801:Humans; D007501:Iron / Q000097:blood*; D008297:Male; D008903:Minerals / Q000097:blood*; D012044:Regression Analysis; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000503:physiopathology
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; C000717427:FGF23 protein, human; C578702:HAMP protein, human; D064451:Hepcidins; D008903:Minerals; D000089703:Fibroblast Growth Factor-23; D007501:Iron