title: Comparison of calcium acetate and sevelamer on vascular function and fibroblast growth factor 23 in CKD patients: a randomized clinical trial.
abstract: BACKGROUND
  Fibroblast growth factor 23 (FGF-23) is a marker of endothelial dysfunction and atherosclerotic complications in patients with chronic kidney disease (CKD). Because previous studies suggested that sevelamer may exert effects on FGF-23 level and endothelial function independently of its phosphate-lowering action, we tested the effect of sevelamer versus calcium acetate on vascular function and FGF-23 levels.
  
  
  METHODS
  Randomized prospective open-label trial.
  
  
  METHODS
  Patients with stage 4 CKD with hyperphosphatemia (n = 100).
  
  
  METHODS
  An 8-week intervention with sevelamer (n = 47) and calcium acetate (n = 53).
  
  
  RESULTS
  The primary study outcome was change in flow-mediated vasodilatation in the forearm. The secondary outcome was change in FGF-23 levels.
  
  
  RESULTS
  Serum phosphate levels decreased in both treatment arms (P < 0.001), but more markedly in the sevelamer group (P < 0.001). Flow-mediated vasodilatation increased from 6.1% to 7.1% (P < 0.001) in sevelamer-treated patients, whereas it was unchanged in the calcium-acetate group (6.0% vs 6.0%). In a combined analysis, treatment-induced changes in flow-mediated vasodilatation were (P < 0.001) associated with simultaneous changes in FGF-23 levels (-27.1% [-33.2% to -8.8%] for the sevelamer group; 3.5% [-8.4% to 12.1%] for the calcium acetate group), as well as with C-reactive protein and fetuin A levels. These relationships were confirmed in multiple regression analysis adjusting for changes in serum phosphate levels and other factors.
  
  
  CONCLUSIONS
  Unblinded randomized controlled study that cannot establish mechanisms of effect.
  
  
  CONCLUSIONS
  In hyperphosphatemic patients with stage 4 CKD, treatment with phosphate lowering induces measurable improvements in flow-mediated vasodilatation. Furthermore, independently of serum phosphate level, FGF-23 level changes induced by phosphate binders are associated with simultaneous changes in flow-mediated vasodilatation. These observations are compatible with the hypothesis that FGF-23 may contribute to vascular dysfunction in this population.
authors.affiliation: Department of Nephrology, Gülhane School of Medicine, Etlik-Ankara, Turkey. mahmutiyilmaz@yahoo.com
authors.forename: Mahmut Ilker
authors.initials: MI
authors.lastname: Yilmaz
authors.forename: Alper
authors.initials: A
authors.lastname: Sonmez
authors.forename: Mutlu
authors.initials: M
authors.lastname: Saglam
authors.forename: Halil
authors.initials: H
authors.lastname: Yaman
authors.forename: Selim
authors.initials: S
authors.lastname: Kilic
authors.forename: Tayfun
authors.initials: T
authors.lastname: Eyileten
authors.forename: Kayser
authors.initials: K
authors.lastname: Caglar
authors.forename: Yusuf
authors.initials: Y
authors.lastname: Oguz
authors.forename: Abdulgaffar
authors.initials: A
authors.lastname: Vural
authors.forename: Mujdat
authors.initials: M
authors.lastname: Yenicesu
authors.forename: Francesca
authors.initials: F
authors.lastname: Mallamaci
authors.forename: Carmine
authors.initials: C
authors.lastname: Zoccali
mesh_terms: D000085:Acetates / Q000494:pharmacology / Q000627:therapeutic use*; D000328:Adult; D017610:Calcium Compounds / Q000494:pharmacology / Q000627:therapeutic use; D002614:Chelating Agents / Q000494:pharmacology / Q000627:therapeutic use; D002908:Chronic Disease; D015897:Comorbidity; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D005542:Forearm / Q000098:blood supply*; D006801:Humans; D054559:Hyperphosphatemia / Q000097:blood / Q000453:epidemiology; D007674:Kidney Diseases / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology; D008875:Middle Aged; D010710:Phosphates / Q000097:blood; D011073:Polyamines / Q000494:pharmacology / Q000627:therapeutic use*; D011446:Prospective Studies; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology*; D000069603:Sevelamer; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D000085:Acetates; D017610:Calcium Compounds; D002614:Chelating Agents; C000717427:FGF23 protein, human; D010710:Phosphates; D011073:Polyamines; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D000069603:Sevelamer; C120662:calcium acetate