Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis
N Engl J Med. 2008 Aug 7;359(6):584-92. doi: 10.1056/NEJMoa0706130.
Orlando M Gutiérrez 1 , Michael Mannstadt, Tamara Isakova, Jose Alejandro Rauh-Hain, Hector Tamez, Anand Shah, Kelsey Smith, Hang Lee, Ravi Thadhani, Harald Jüppner, Myles Wolf
1 Renal Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, USA.
DOI: 10.1056/NEJMoa0706130
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.
2008 Massachusetts Medical Society
Biomarkers / blood
Fibroblast Growth Factor-23
Fibroblast Growth Factors / blood*
Kidney Failure, Chronic / blood*
Kidney Failure, Chronic / ethnology
Kidney Failure, Chronic / mortality
Kidney Failure, Chronic / therapy
Phosphates / blood
Proportional Hazards Models
Racial Groups
Renal Dialysis / mortality*
FGF23 protein, human
Fibroblast Growth Factors
R01DK076116/DK/NIDDK NIH HHS/United States
K30RR02229207/RR/NCRR NIH HHS/United States
K23 RR017376/RR/NCRR NIH HHS/United States
K23RR017376/RR/NCRR NIH HHS/United States
K08 DK081669/DK/NIDDK NIH HHS/United States