The role of FGF23 in CKD—with or without Klotho

Abstract

During the past few years, fibroblast growth factor 23 (FGF23) has emerged as a central player of disordered mineral metabolism in patients with chronic kidney disease (CKD). The physiological actions of FGF23 are to promote phosphaturia, decrease production of 1,25-dihydroxyvitamin D and suppress secretion of parathyroid hormone mediated through FGF receptors and the co-receptor Klotho. Recent epidemiological studies demonstrate strong associations between elevated FGF23 levels in patients with CKD and poor clinical outcomes. In patients with end-stage renal disease, markedly increased levels of FGF23 fail to exert Klotho-dependent effects owing to the absence of a functioning kidney and downregulation of the parathyroid complex of Klotho and FGF receptor 1. In this setting, FGF23 may exert a toxic effect on the cardiovascular system in a Klotho-independent manner. Future research should examine whether treatment to attenuate the pathogenic action of FGF23 provides survival benefits in patients with CKD.