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Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis.

Publication ,  Journal Article
Gutiérrez, OM; Mannstadt, M; Isakova, T; Rauh-Hain, JA; Tamez, H; Shah, A; Smith, K; Lee, H; Thadhani, R; Jüppner, H; Wolf, M
Published in: N Engl J Med
August 7, 2008

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.

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Published In

N Engl J Med

DOI

EISSN

1533-4406

Publication Date

August 7, 2008

Volume

359

Issue

6

Start / End Page

584 / 592

Location

United States

Related Subject Headings

  • Risk Factors
  • Renal Dialysis
  • Racial Groups
  • Prospective Studies
  • Proportional Hazards Models
  • Phosphates
  • Odds Ratio
  • Multivariate Analysis
  • Middle Aged
  • Male
 

Citation

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Gutiérrez, O. M., Mannstadt, M., Isakova, T., Rauh-Hain, J. A., Tamez, H., Shah, A., … Wolf, M. (2008). Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis. N Engl J Med, 359(6), 584–592. https://doi.org/10.1056/NEJMoa0706130
Gutiérrez, Orlando M., Michael Mannstadt, Tamara Isakova, Jose Alejandro Rauh-Hain, Hector Tamez, Anand Shah, Kelsey Smith, et al. “Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis.N Engl J Med 359, no. 6 (August 7, 2008): 584–92. https://doi.org/10.1056/NEJMoa0706130.
Gutiérrez OM, Mannstadt M, Isakova T, Rauh-Hain JA, Tamez H, Shah A, et al. Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis. N Engl J Med. 2008 Aug 7;359(6):584–92.
Gutiérrez, Orlando M., et al. “Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis.N Engl J Med, vol. 359, no. 6, Aug. 2008, pp. 584–92. Pubmed, doi:10.1056/NEJMoa0706130.
Gutiérrez OM, Mannstadt M, Isakova T, Rauh-Hain JA, Tamez H, Shah A, Smith K, Lee H, Thadhani R, Jüppner H, Wolf M. Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis. N Engl J Med. 2008 Aug 7;359(6):584–592.

Published In

N Engl J Med

DOI

EISSN

1533-4406

Publication Date

August 7, 2008

Volume

359

Issue

6

Start / End Page

584 / 592

Location

United States

Related Subject Headings

  • Risk Factors
  • Renal Dialysis
  • Racial Groups
  • Prospective Studies
  • Proportional Hazards Models
  • Phosphates
  • Odds Ratio
  • Multivariate Analysis
  • Middle Aged
  • Male