FGF23-parathyroid interaction: implications in chronic kidney disease.
Over the past few years there have been considerable advances in our understanding of the physiological regulation of mineral homeostasis. One of the most important breakthroughs is the identification of fibroblastic growth factor 23 (FGF23) and its role as a key regulator of phosphate and 1,25-dihydroxyvitamin D metabolism. FGF23 exerts its biological functions by binding to its cognate receptor in the presence of Klotho as a cofactor. FGF23 principally acts on the kidney to induce urinary phosphate excretion and suppresses 1,25-dihydroxyvitamin D synthesis, thereby indirectly modulating parathyroid hormone secretion. FGF23 also acts directly on the parathyroid to decrease parathyroid hormone synthesis and secretion. In patients with chronic kidney disease, FGF23 levels increase progressively to compensate for phosphate retention, but these elevated FGF23 levels fail to suppress the secretion of parathyroid hormone, particularly in the setting of uremia. Recent data suggest that this parathyroid resistance to FGF23 may be caused by decreased expression of Klotho-FGFR1 complex in hyperplastic parathyroid glands. This review summarizes recent insights into the role of FGF23 in mineral homeostasis and discusses the involvement of its direct and indirect interaction with the parathyroid gland, particularly focusing on the pathophysiology of secondary hyperparathyroidism in chronic kidney disease.
Komaba
Hirotaka
H
Division of Nephrology and Kidney Center, Kobe University School of Medicine, Kobe, Japan.
Fukagawa
Masafumi
M
D000818:Animals; D002908:Chronic Disease; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000502:physiology*; D006801:Humans; D006965:Hyperplasia / Q000209:etiology; D007674:Kidney Diseases / Q000209:etiology*; D010280:Parathyroid Glands / Q000473:pathology; D010281:Parathyroid Hormone / Q000502:physiology*; D014511:Uremia / Q000209:etiology
C000717427:FGF23 protein, human; D010281:Parathyroid Hormone; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23