[HTML][HTML] Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis

OM Gutiérrez, M Mannstadt, T Isakova… - … England Journal of …, 2008 - Mass Medical Soc
OM Gutiérrez, M Mannstadt, T Isakova, JA Rauh-Hain, H Tamez, A Shah, K Smith, H Lee
New England Journal of Medicine, 2008Mass Medical Soc
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 …
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.
The New England Journal Of Medicine