• Tamara Isakova, Huiliang Xie, Wei Yang, Dawei Xie, Amanda Hyre Anderson, Julia Scialla, Patricia Wahl, Orlando M Gutiérrez, Susan Steigerwalt, Jiang He, Stanley Schwartz, Joan Lo, Akinlolu Ojo, James Sondheimer, Chi-yuan Hsu, James Lash, Mary Leonard, John W Kusek, Harold I Feldman, Myles Wolf, and Chronic Renal Insufficiency Cohort (CRIC) Study Group.
• Division of Nephrology and Hypertension, Department of Medicine, University of Miami, Miller School of Medicine, 1120 NW 14th St, Miami, FL 33136, USA.
• JAMA. 2011 Jun 15; 305 (23): 243224392432-9.

ContextA 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.ObjectiveTo evaluate FGF-23 as a risk factor for adverse outcomes in patients with chronic kidney disease.Design, Setting, And ParticipantsA 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.Main Outcome MeasuresAll-cause mortality and end-stage renal disease.ResultsAt 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).ConclusionElevated 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.

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