Fibroblast Growth Factor 23 and Risks of Mortality and End-Stage Renal Disease in Patients With Chronic Kidney Disease

Study Questions:

Do plasma levels of fibroblast growth factor 23 (FGF-23) predict end-stage renal disease (ESRD) and mortality in patients with chronic kidney disease (CKD)?

Methods:

This was a prospective study of 3,879 participants with CKD stages 2 through 4, who enrolled in the Chronic Renal Insufficiency Cohort between June 2003 and September 2008. The main outcome was all-cause mortality and ESRD.

Results:

During a median follow-up of 3.5 years, 266 participants died (20.3/1,000 person-years) and 410 reached ESRD (33.0/1,000 person-years). In adjusted analyses, higher levels of FGF-23 were independently associated with a greater risk of death, with a hazard ratio (HR) of 1.5 per standard deviation (SD) of natural log-transformed FGF-23. Mortality risk increased by quartile of FGF-23: the HR was 1.3 for the second quartile, 2.0 for the third quartile, and 3.0 for the fourth quartile. Elevated FGF-13 was independently associated with a significantly higher risk of ESRD among participants with GFR between 30 and 44 ml/min/1.73 m2 (HR, 1.3 per SD of natural log-transformed FGF-23) and 45 ml/min/1.73 m2 or higher (HR, 1.7), but not less than 30 ml/min/1.73 m2.

Conclusions:

Elevated FGF-23 is an independent risk factor for ESRD in patients with relatively preserved kidney function, and for mortality across the spectrum of CKD.

Perspective:

Plasma levels of FGF-23 are known to rise with renal failure, possibly as a mechanism to maintain normal serum phosphate levels. Previous studies have shown that higher levels of FGF-23 in patients undergoing dialysis are associated with increased mortality. The current study expands this observation by demonstrating that FGF-23 is predictive of adverse outcomes even in patients with relatively mild kidney disease. Furthermore, the adjusted analysis suggests that FGF-23 may actually be a mediator of adverse events rather than just a biomarker of more severe renal dysfunction. This raises the possibility that therapeutic targeting of FGF-23 may be beneficial in patients with kidney disease.

Keywords: Renal Dialysis, Follow-Up Studies, Biological Markers, Kidney Failure, Chronic, Risk Factors, Fibroblast Growth Factors, Renal Insufficiency, Chronic


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