Abstract
Elevated serum levels of the phosphaturic hormone fibroblast growth factor 23 (FGF23) are strongly associated with chronic kidney disease (CKD) progression and mortality, and are also independently associated with left ventricular hypertrophy, a major contributor to cardiovascular disease (CVD) and death in CKD patients. As FGF23 levels rise long before serum phosphate in CKD, FGF23 is a more sensitive biomarker of disordered phosphate metabolism and its associated renal and CVD toxicity.
This review will address the novel possibility that FGF23 contributes directly to CVD in patients with CKD. We will summarize the basic principles of FGF-mediated signal transduction and review the current literature on effects of FGF family members on the heart as well as FGF23 signaling in 'classic' target cells, in order to flesh out the novelty underlying FGF23-induced cell signaling in the heart. By doing so we will speculate on why such a direct cardiac effect has not been described before, and suggest a novel target for pharmacological intervention.
By demonstrating direct pathological effects of FGF23 on the heart, novel findings from a recent translational study reposition FGF23 from biomarker of risk, to mechanism of disease. Therefore the pharmacological interference with FGF23 and/or its cardiac receptor in CKD patients could be beneficial to prevent or treat CVD.
