title: Fibroblast growth factor 23 and risks of mortality and end-stage renal disease in patients with chronic kidney disease.
abstract: BACKGROUND
  A high level of the phosphate-regulating hormone fibroblast growth factor 23 (FGF-23) is associated with mortality in patients with end-stage renal disease, but little is known about its relationship with adverse outcomes in the much larger population of patients with earlier stages of chronic kidney disease.
  
  
  OBJECTIVE
  To evaluate FGF-23 as a risk factor for adverse outcomes in patients with chronic kidney disease.
  
  
  METHODS
  A prospective study of 3879 participants with chronic kidney disease stages 2 through 4 who enrolled in the Chronic Renal Insufficiency Cohort between June 2003 and September 2008.
  
  
  METHODS
  All-cause mortality and end-stage renal disease.
  
  
  RESULTS
  At study enrollment, the mean (SD) estimated glomerular filtration rate (GFR) was 42.8 (13.5) mL/min/1.73 m(2), and the median FGF-23 level was 145.5 RU/mL (interquartile range [IQR], 96-239 reference unit [RU]/mL). During a median follow-up of 3.5 years (IQR, 2.5-4.4 years), 266 participants died (20.3/1000 person-years) and 410 reached end-stage renal disease (33.0/1000 person-years). In adjusted analyses, higher levels of FGF-23 were independently associated with a greater risk of death (hazard ratio [HR], per SD of natural log-transformed FGF-23, 1.5; 95% confidence interval [CI], 1.3-1.7). Mortality risk increased by quartile of FGF-23: the HR was 1.3 (95% CI, 0.8-2.2) for the second quartile, 2.0 (95% CI, 1.2-3.3) for the third quartile, and 3.0 (95% CI, 1.8-5.1) for the fourth quartile. Elevated fibroblast growth factor 23 was independently associated with significantly higher risk of end-stage renal disease among participants with an estimated GFR between 30 and 44 mL/min/1.73 m(2) (HR, 1.3 per SD of FGF-23 natural log-transformed FGF-23; 95% CI, 1.04-1.6) and 45 mL/min/1.73 m(2) or higher (HR, 1.7; 95% CI, 1.1-2.4), but not less than 30 mL/min/1.73 m(2).
  
  
  CONCLUSIONS
  Elevated FGF-23 is an independent risk factor for end-stage renal disease in patients with relatively preserved kidney function and for mortality across the spectrum of chronic kidney disease.
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine, University of Miami, Miller School of Medicine, 1120 NW 14th St, Miami, FL 33136, USA.
authors.forename: Tamara
authors.initials: T
authors.lastname: Isakova
authors.forename: Huiliang
authors.initials: H
authors.lastname: Xie
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
authors.forename: Dawei
authors.initials: D
authors.lastname: Xie
authors.forename: Amanda Hyre
authors.initials: AH
authors.lastname: Anderson
authors.forename: Julia
authors.initials: J
authors.lastname: Scialla
authors.forename: Patricia
authors.initials: P
authors.lastname: Wahl
authors.forename: Orlando M
authors.initials: OM
authors.lastname: Gutiérrez
authors.forename: Susan
authors.initials: S
authors.lastname: Steigerwalt
authors.forename: Jiang
authors.initials: J
authors.lastname: He
authors.forename: Stanley
authors.initials: S
authors.lastname: Schwartz
authors.forename: Joan
authors.initials: J
authors.lastname: Lo
authors.forename: Akinlolu
authors.initials: A
authors.lastname: Ojo
authors.forename: James
authors.initials: J
authors.lastname: Sondheimer
authors.forename: Chi-yuan
authors.initials: CY
authors.lastname: Hsu
authors.forename: James
authors.initials: J
authors.lastname: Lash
authors.forename: Mary
authors.initials: M
authors.lastname: Leonard
authors.forename: John W
authors.initials: JW
authors.lastname: Kusek
authors.forename: Harold I
authors.initials: HI
authors.lastname: Feldman
authors.forename: Myles
authors.initials: M
authors.lastname: Wolf
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood*; D002908:Chronic Disease; D018450:Disease Progression; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D005919:Glomerular Filtration Rate; D006801:Humans; D007674:Kidney Diseases / Q000097:blood* / Q000401:mortality*; D007676:Kidney Failure, Chronic / Q000097:blood / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D015415:Biomarkers; C000717427:FGF23 protein, human; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23