title: Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis.
abstract: BACKGROUND
  Fibroblast growth factor 23 (FGF-23) is a hormone that increases the rate of urinary excretion of phosphate and inhibits renal production of 1,25-dihydroxyvitamin D, thus helping to mitigate hyperphosphatemia in patients with kidney disease. Hyperphosphatemia and low 1,25-dihydroxyvitamin D levels are associated with mortality among patients with chronic kidney disease, but the effect of the level of FGF-23 on mortality is unknown.
  
  
  METHODS
  We examined mortality according to serum phosphate levels in a prospective cohort of 10,044 patients who were beginning hemodialysis treatment and then analyzed FGF-23 levels and mortality in a nested case-control sample of 200 subjects who died and 200 who survived during the first year of hemodialysis treatment. We hypothesized that increased FGF-23 levels at the initiation of hemodialysis would be associated with increased mortality.
  
  
  RESULTS
  Serum phosphate levels in the highest quartile (>5.5 mg per deciliter [1.8 mmol per liter]) were associated with a 20% increase in the multivariable adjusted risk of death, as compared with normal levels (3.5 to 4.5 mg per deciliter [1.1 to 1.4 mmol per liter]) (hazard ratio, 1.2; 95% confidence interval [CI], 1.1 to 1.4). Median C-terminal FGF-23 (cFGF-23) levels were significantly higher in case subjects than in controls (2260 vs. 1406 reference units per milliliter, P<0.001). Multivariable adjusted analyses showed that increasing FGF-23 levels were associated with a monotonically increasing risk of death when examined either on a continuous scale (odds ratio per unit increase in log-transformed cFGF-23 values, 1.8; 95% CI, 1.4 to 2.4) or in quartiles, with quartile 1 as the reference category (odds ratio for quartile 2, 1.6 [95% CI, 0.8 to 3.3]; for quartile 3, 4.5 [95% CI, 2.2 to 9.4]; and for quartile 4, 5.7 [95% CI, 2.6 to 12.6]).
  
  
  CONCLUSIONS
  Increased FGF-23 levels appear to be independently associated with mortality among patients who are beginning hemodialysis treatment. Future studies might investigate whether FGF-23 is a potential biomarker that can be used to guide strategies for the management of phosphorus balance in patients with chronic kidney disease.
authors.affiliation: Renal Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, USA.
authors.forename: Orlando M
authors.initials: OM
authors.lastname: Gutiérrez
authors.forename: Michael
authors.initials: M
authors.lastname: Mannstadt
authors.forename: Tamara
authors.initials: T
authors.lastname: Isakova
authors.forename: Jose Alejandro
authors.initials: JA
authors.lastname: Rauh-Hain
authors.forename: Hector
authors.initials: H
authors.lastname: Tamez
authors.forename: Anand
authors.initials: A
authors.lastname: Shah
authors.forename: Kelsey
authors.initials: K
authors.lastname: Smith
authors.forename: Hang
authors.initials: H
authors.lastname: Lee
authors.forename: Ravi
authors.initials: R
authors.lastname: Thadhani
authors.forename: Harald
authors.initials: H
authors.lastname: Jüppner
authors.forename: Myles
authors.initials: M
authors.lastname: Wolf
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000208:ethnology / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D010710:Phosphates / Q000097:blood; D016016:Proportional Hazards Models; D011446:Prospective Studies; D044469:Racial Groups; D006435:Renal Dialysis / Q000401:mortality*; D012307:Risk Factors
chemical_list: D015415:Biomarkers; C000717427:FGF23 protein, human; D010710:Phosphates; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23