title: Effects of intravenous iron on fibroblast growth factor 23 (FGF23) in haemodialysis patients: a randomized controlled trial.
abstract: Intravenous iron affects serum levels of intact fibroblast growth factor-23 (iFGF23) and its cleavage product c-terminal FGF23 (cFGF23) in iron-deficient people with normal renal function. We hypothesized that intravenous iron modulates iFGF23 and cFGF23 in haemodialysis patients differently according to the type of iron used.
  
  
  
  Prevalent, stable haemodialysis patients requiring protocol-based intravenous iron therapy were randomized to a single 200 mg dose of either ferric carboxymaltose (FCM) or iron sucrose (IS). The primary outcome was change in iFGF23 and cFGF23 from pre-infusion to Day 2 post-infusion. Serum hepcidin, ferritin and phosphate were also measured. Pair-wise comparisons utilised the Wilcoxon rank sum test; linear mixed models with an interaction term for treatment and time evaluated between-group effects.
  
  
  
  Forty-two participants completed the study. In those randomized to FCM (n = 22), median (interquartile range) values pre-infusion and Day 2, respectively, were 843 pg/mL (313-1922) and 576 pg/mL (356-1296, p = 0.05) for iFGF23, 704RU/mL (475-1204) and 813RU/mL (267-1156, p = 0.04) for cFGF23, and 1.53 mmol/L (1.14-1.71) and 1.37 (1.05-1.67, p = 0.03) for phosphate. These parameters did not change following IS. Both serum ferritin (p < 0.001) and hepcidin (p < 0.001) increased in both groups, and the increase in hepcidin was greater in the FCM group (p = 0.03 for between-group difference).
  
  
  
  Contrary to iron-deficient people with normal renal function, haemodialysis patients given protocol-driven intravenous FCM demonstrated a fall in iFGF23 and a rise in cFGF23, changes not evident with IS. This suggests a differential effect of intravenous iron treatment according to both formulation and renal function.
  
  
  
  Australian and New Zealand Clinical Trials Register ACTRN12614000548639 . Registered 22 May 2014 (retrospectively registered).
authors.affiliation: Eastern Health Clinical School, Monash University, Box Hill, VIC, Australia.|Department of Renal Medicine, Eastern Health, Box Hill, VIC, Australia.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Roberts
authors.affiliation: Eastern Health Clinical School, Monash University, Box Hill, VIC, Australia.|Department of Renal Medicine, Eastern Health, Box Hill, VIC, Australia.
authors.forename: Louis
authors.initials: L
authors.lastname: Huang
authors.affiliation: Eastern Health Clinical School, Monash University, Box Hill, VIC, Australia.|Department of Renal Medicine, Eastern Health, Box Hill, VIC, Australia.
authors.forename: Darren
authors.initials: D
authors.lastname: Lee
authors.affiliation: Eastern Health Clinical School, Monash University, Box Hill, VIC, Australia.|Department of Renal Medicine, Eastern Health, Box Hill, VIC, Australia.
authors.forename: Robert
authors.initials: R
authors.lastname: MacGinley
authors.affiliation: Department of Renal Medicine, Eastern Health, Box Hill, VIC, Australia.
authors.forename: Stefanie M A
authors.initials: SM
authors.lastname: Troster
authors.affiliation: Eastern Health Clinical School, Monash University, Box Hill, VIC, Australia.|Department of Renal Medicine, Eastern Health, Box Hill, VIC, Australia.
authors.forename: Annette B
authors.initials: AB
authors.lastname: Kent
authors.affiliation: Institute of Pharmaceutical Science, King's College, London, UK.
authors.forename: Sukhvinder S
authors.initials: SS
authors.lastname: Bansal
authors.affiliation: Department of Renal Medicine, King's College Hospital, London, UK.
authors.forename: Iain C
authors.initials: IC
authors.lastname: Macdougall
authors.affiliation: Eastern Health Clinical School, Monash University, Box Hill, VIC, Australia. Lawrence.McMahon@easternhealth.org.au.|Department of Renal Medicine, Eastern Health, Box Hill, VIC, Australia. Lawrence.McMahon@easternhealth.org.au.
authors.forename: Lawrence P
authors.initials: LP
authors.lastname: McMahon
mesh_terms: D061605:Administration, Intravenous; D000368:Aged; D005260:Female; D005290:Ferric Compounds / Q000008:administration & dosage*; D000077605:Ferric Oxide, Saccharated; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood* / Q000187:drug effects; D005937:Glucaric Acid / Q000008:administration & dosage*; D006397:Hematinics / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008320:Maltose / Q000008:administration & dosage / Q000031:analogs & derivatives*; D008875:Middle Aged; D006435:Renal Dialysis; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000628:therapy*
chemical_list: C000717427:FGF23 protein, human; D005290:Ferric Compounds; D006397:Hematinics; D005346:Fibroblast Growth Factors; C522335:ferric carboxymaltose; D008320:Maltose; D000089703:Fibroblast Growth Factor-23; D000077605:Ferric Oxide, Saccharated; D005937:Glucaric Acid
keywords: Fibroblast growth factor-23; Haemodialysis; Hepcidin; Iron infusion; Randomized controlled trial