Fibroblast Growth Factor 23 in Autosomal Dominant Polycystic Kidney Disease

Fibroblast growth factor 23 (FGF23) is a 23-kDa protein that is synthesized in bone mainly by osteocytes and less in the spleen and brain, which has a key role in the “bone-kidney/parathyroid” axis and most importantly regulating serum phosphate and calcium. Fibroblast growth factor 23 acts mainly as a phosphaturic factor and a suppressor of 1α-hydroxylase activity in the kidney. Moreover, it also inhibits 1α-hydroxylase activity whereas it stimulates the 24-hydroxylase activity, thus leading to a decreased 1,25-dihydroxyvitamin D serum level. These two pathways account together for the hypophosphatemic effect of FGF23. Fibroblast growth factor 23 indirectly mediates secretion of parathyroid hormone (PTH) and also has a direct effect on the parathyroid gland to suppresses PTH synthesis and secretion. However, PTH induces expression and secretion of FGF23 both directly and indirectly. Fibroblast growth factor 23 can stimulate local expression of 1α-hydroxylase in the parathyroid gland, suggesting that it can also indirectly downregulate PTH synthesis through an increased local production of calcitriol.