The role of FGF23 in CKD--with or without Klotho.
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.
Division of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine, Isehara 259-1193, Japan.
Hirotaka
H
Komaba
Masafumi
M
Fukagawa
D015415:Biomarkers; D001847:Bone Diseases / Q000378:metabolism; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000502:physiology*; D005966:Glucuronidase / Q000378:metabolism; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000209:etiology; D007676:Kidney Failure, Chronic / Q000378:metabolism; D000090265:Klotho Proteins; D010281:Parathyroid Hormone / Q000097:blood; D051436:Renal Insufficiency, Chronic / Q000378:metabolism*
D015415:Biomarkers; C000717427:FGF23 protein, human; D010281:Parathyroid Hormone; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D005966:Glucuronidase; D000090265:Klotho Proteins