Endocrine Abstracts

FGF23 secretion is increased in response to 1,25(OH)2 vitaminD3 (1,25D) and an oral phosphorus (P) load. Patients with chronic kidney disease (CKD) are unable to excrete their dietary P which contributes to an increased secretion of the two major phosphaturic hormones, PTH and FGF23. The increased FGF23 would normally bind to its receptor, klotho-FGFR1 in the renal tubules to increase P clearance and decrease the synthesis of 1,25D. Increased FGF23, P and PTH levels are all associated with an increased mortality in CKD. Physiologically, FGF23 acts on its receptor klotho-FGFR1 in the parathyroid to decrease PTH expression and parathyroid cell proliferation but in advanced CKD there is a decrease in the expression of klotho-FGFR1 both in the parathyroid in the kidney. This is associated with high levels of both FGF23 and PTH. In turn, the high levels of PTH act on bone cells to increase FGF23. We recently showed that PTH acts directly on osteoblast like cells to increase FGF23 expression. Remarkably, parathyroidectomy in rats both prevents and corrects the high FGF23 due to short-term experimental uremia. In patients a decrease in PTH leads to a decrease in serum FGF23. Therefore, in CKD, the high levels of PTH are necessary to maintain the high levels of FGF23. Experimental CKD is associated with low renal klotho levels and the administration of klotho has been shown to bind to TGFβ1 and improve renal function. Dialysis patients’ course is often complicated by left ventricular hypertrophy (LVH) and cardiac failure. FGF23 acts directly on cardiomyocytes to cause LVH and the progression to LVH in CKD correlates with the high levels of FGF23. Moreover, administration of an FGFR blocker attenuated LVH in experimental CKD. Therefore, FGF23 expression is increased by P, 1,25D and PTH and it has important actions on the kidney, parathyroid and heart.

Declaration of interest: The author declares that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported, however funding details are unavailable.