title: Cinacalcet lowering of serum fibroblast growth factor-23 concentration may be independent from serum Ca, P, PTH and dose of active vitamin D in peritoneal dialysis patients: a randomized controlled study.
abstract: BACKGROUND
  Elevated serum level of fibroblast growth factor-23 (FGF23) is associated with adverse outcomes in dialyzed patients.
  
  
  OBJECTIVE
  The CUPID study compared the efficacy of a cinacalcet-based regimen with conventional care (vitamin D and P binders) for achieving the stringent NKF-K/DOQI targets for peritoneal dialysis (PD) patients. Additionally, we analyzed change in FGF23 levels between two treatments to explore the cinacalcet effect in lowering FGF23.
  
  
  METHODS
  Multicenter, open-labeled, randomized controlled study.
  
  
  METHODS
  Seven university-affiliated hospitals in Korea.
  
  
  METHODS
  Overall, 66 peritoneal dialysis patients were enrolled.
  
  
  METHODS
  Sixty six patients were randomly assigned to treatment with either cinacalcet + oral vitamin D (cinacalcet group, n = 33) or oral vitamin D alone (control group, n = 33) to achieve K/DOQI targets. CUPID included a 4-week screening for vitamin D washout, a 12-week dose-titration, and a 4-week assessment phases. We calculated mean values of iPTH, Ca, P, Ca x P, during assessment phase and final FGF23 to assess the outcome.
  
  
  METHODS
  Achievement of >30% reduction of iPTH from baseline (primary) and FGF23 reduction (secondary).
  
  
  RESULTS
  72.7% (n = 24) of the cinacalcet group and 93.9% (n = 31) of the control group completed the study. Cinacalcet group received 30.2 ± 18.0 mg/day of cinacalcet and 0.13 ± 0.32 μg/d oral vitamin D (P < 0.001 vs. control with 0.27 ± 0.18 μg/d vitamin D). The proportion of patients who reached the primary endpoint was not statistically different (48.5% vs. 51.5%, cinacalcet vs. control, P = 1.000). After treatment, cinacalcet group experienced a significant reduction in FGF23 levels (median value from 3,960 to 2,325 RU/ml, P = 0.002), while an insignificant change was shown for control group (from 2,085 to 2,415 RU/ml). The percent change of FGF23 after treatment was also significantly different between the two groups (- 42.54% vs. 15.83%, P = 0.008). After adjustment, cinacalcet treatment was independently associated with the serum FGF23 reduction.
  
  
  CONCLUSIONS
  Cinacalcet treatment was independently associated with the reduction of FGF23 in our PD patients.
  
  
  BACKGROUND
  Controlled trials NCT01101113.
authors.affiliation: Department of Internal Medicine, Seoul National University, Seoul, Korea.
authors.forename: Hyo Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: Hyunsuk
authors.initials: H
authors.lastname: Kim
authors.forename: Nara
authors.initials: N
authors.lastname: Shin
authors.forename: Ki Young
authors.initials: KY
authors.lastname: Na
authors.forename: Yong Lim
authors.initials: YL
authors.lastname: Kim
authors.forename: Daejung
authors.initials: D
authors.lastname: Kim
authors.forename: Jae Hyun
authors.initials: JH
authors.lastname: Chang
authors.forename: Young Rim
authors.initials: YR
authors.lastname: Song
authors.forename: Young-Hwan
authors.initials: YH
authors.lastname: Hwang
authors.forename: Yon Su
authors.initials: YS
authors.lastname: Kim
authors.forename: Curie
authors.initials: C
authors.lastname: Ahn
authors.forename: Joongyub
authors.initials: J
authors.lastname: Lee
authors.forename: Kook-Hwan
authors.initials: KH
authors.lastname: Oh
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002118:Calcium / Q000097:blood*; D000069449:Cinacalcet; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000037:antagonists & inhibitors / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009281:Naphthalenes / Q000494:pharmacology*; D010281:Parathyroid Hormone / Q000097:blood*; D010530:Peritoneal Dialysis / Q000009:adverse effects; D010758:Phosphorus / Q000097:blood*; D014807:Vitamin D / Q000097:blood*
chemical_list: D015415:Biomarkers; C000717427:FGF23 protein, human; D009281:Naphthalenes; D010281:Parathyroid Hormone; D014807:Vitamin D; D010758:Phosphorus; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D002118:Calcium; D000069449:Cinacalcet