New insights into the role of fibroblast growth factor 23 in chronic kidney disease.
Fibroblast growth factor 23 (FGF23) is a recently identified bone-derived hormone that regulates phosphate and 1,25-dihydroxyvitamin D metabolism. FGF23 principally acts in the kidney to induce urinary phosphate excretion and suppress 1,25-dihydroxyvitamin D synthesis in the presence of FGF receptor 1 (FGFR1) and its coreceptor Klotho. FGF23 also acts in the parathyroid to decrease parathyroid hormone synthesis and secretion. In patients with chronic kidney disease (CKD), circulating FGF23 levels are progressively increased to compensate for persistent phosphate retention, but this results in reduced renal production of 1,25-dihydroxyvitamin D and leads to hypersecretion of parathyroid hormone. In patients undergoing dialysis, FGF23 levels are markedly elevated in response to hyperphosphatemia and active vitamin D therapy, but fail to suppress the secretion of parathyroid hormone, presumably due to decreased expression of the Klotho-FGFR1 complex. In these patients, FGF23 can be used as a predictor of future development of refractory hyperparathyroidism. FGF23 also plays a central role in the pathogenesis of post-transplant hypophosphatemia in kidney transplant recipients. Furthermore, recent studies suggest that FGF23 could be an independent predictor of mortality in dialysis patients, indicating its potential role as a sensitive biomarker of disordered phosphate metabolism. This brief review summarizes recent insights into the role of FGF23 in the pathogenesis of mineral and bone disorders in CKD.
Nakai
Kentaro
K
Division of Nephrology and Kidney Center, Kobe University School of Medicine, Kobe, Japan.
Komaba
Hirotaka
H
Fukagawa
Masafumi
M
D000818:Animals; D002908:Chronic Disease; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000502:physiology*; D005966:Glucuronidase / Q000378:metabolism; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism*; D007676:Kidney Failure, Chronic / Q000378:metabolism; D016030:Kidney Transplantation; D000090265:Klotho Proteins; D010710:Phosphates / Q000378:metabolism; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000378:metabolism; D014807:Vitamin D / Q000378:metabolism
C000717427:FGF23 protein, human; D010710:Phosphates; D014807:Vitamin D; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D051496:Receptor, Fibroblast Growth Factor, Type 1; D005966:Glucuronidase; D000090265:Klotho Proteins