[CKD-MBD (Chronic Kidney Disease-Mineral and Bone Disorder). Role of FGF23-Klotho axis in CKD-MBD].
FGF23 is a novel bone-derived hormone that plays an important role in the regulation of phosphate and 1,25-dihydroxy vitamin D metabolism. FGF23 binds to FGF receptor1 (FGFR1) -Klotho complex in the kidney and thereby induces phosphaturia and suppresses 1,25-dihydroxyvitamin D synthesis. 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 secondary hyperparathyroidism. In patients undergoing dialysis, FGF23 levels are markedly elevated in response to hyperphosphatemia and active vitamin D therapy, which in turn cause hypophosphatemia and reduced 1,25-dihydroxyvitamin D after kidney transplantation. FGF23 also acts directly on the parathyroid to decrease parathyroid hormone synthesis and secretion; however, in end-stage CKD patients, markedly elevated FGF23 fails to suppress the secretion of parathyroid hormone. Recent data suggest that this parathyroid resistance to FGF23 may be caused by decreased expression of FGFR1-Klotho complex in hyperplastic parathyroid glands. Further elucidation of FGF23-Klotho axis will help us to improve the understanding of the pathogenesis of CKD-mineral and bone disorder.
Komaba
Hirotaka
H
Division of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine.
D015519:Bone Density; D001851:Bone Diseases, Metabolic / Q000209:etiology* / Q000378:metabolism; D002908:Chronic Disease; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000502:physiology*; D005966:Glucuronidase / Q000502:physiology*; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000209:etiology; D007674:Kidney Diseases / Q000209:etiology*; D000090265:Klotho Proteins; D010281:Parathyroid Hormone / Q000378:metabolism; D010758:Phosphorus / Q000378:metabolism; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000502:physiology; D014807:Vitamin D / Q000378:metabolism
C000717427:FGF23 protein, human; D010281:Parathyroid Hormone; D014807:Vitamin D; D010758:Phosphorus; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1; D005966:Glucuronidase; D000090265:Klotho Proteins