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

Abstract

Fibroblast growth factor 23 (FGF-23) is an endocrine hormone that regulates phosphorus metabolism. Circulating levels of FGF-23 increase progressively as kidney function declines, eventually reaching concentrations in patients with chronic kidney disease that are among the highest in any condition commonly encountered in clinical practice.¹ Fibroblast growth factor 23 levels increase in chronic kidney disease as an appropriate physiological adaptation to maintain neutral phosphate balance and normal serum phosphate levels in the setting of reduced renal capacity for phosphate excretion. Preventing increases in serum phosphate is likely beneficial in chronic kidney disease given reports of greater risk of adverse renal and cardiovascular outcomes in association with overt hyperphosphatemia and even modest elevations in serum phosphate within the normal range.^2,3 However, small studies suggest that an elevated FGF-23 level is an independent risk factor for mortality among patients undergoing dialysis,^4,5 and for more rapid loss of kidney function in earlier stages of chronic kidney disease.^6,7 Whether FGF-23 is associated with greater risks of mortality and end-stage renal disease in the much larger population of patients with earlier stages of chronic kidney disease is unknown. We tested the hypothesis that an elevated FGF-23 level is an independent risk factor for death and end-stage renal disease in a large, racially and ethnically diverse, prospective cohort study of individuals with chronic kidney disease stages 2 through 4.