Fibroblast growth factor 23: associations with cardiovascular disease and mortality in chronic kidney disease

Abstract

Fibroblast growth factor-23 (FGF-23) has emerged as an important hormone involved in phosphorus and vitamin D homeostasis. Chronic kidney disease (CKD) is the most common clinical condition in which FGF-23 levels are persistently and markedly elevated. Abnormal phosphate homeostasis and high circulating levels of FGF-23 are early complications of CKD. Although increases in FGF-23 levels may help maintain serum phosphate levels in the normal range in CKD, the long-term effects of its sustained elevated levels are unclear. Patients with CKD have high risks of developing end-stage renal disease (ESRD), cardiovascular disease, and premature death. Recent prospective studies in populations with predialysis CKD, ESRD on hemodialysis, and kidney transplant recipients demonstrate that elevated FGF-23 levels are independently associated with cardiovascular events and mortality. It was originally thought that FGF-23 was only a biomarker of disturbed phosphate balance; however, recent studies have shown that FGF-23 can have a direct effect on the heart, inducing left ventricular hypertrophy. This suggests that elevated FGF-23 levels may be a novel mechanism that explains the poor cardiovascular outcomes in CKD patients. Interventional studies are required in order to clarify the relation of causality between FGF-23 and cardiovascular mortality in this population.