A short story of Klotho and FGF23: a deuce of dark side or the savior?
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Fibroblast growth factor 23 (FGF23) is an osteocyte and osteoblast derived peptide hormone, which requires Klotho as a cofactor for its biologic actions. FGF23 acts as a phosphaturic agent and it is capable of reducing serum inorganic phosphate (Pi) via direct inhibition of renal NaPi-2a transporter in the proximal tubuli, as well as indirectly, via the suppression of calcitriol synthesis. In patients with chronic kidney disease (CKD), circulating FGF23 levels are markedly elevated, while Klotho production is decreased. Experimental observations indicating that lack of activities of both Klotho and FGF23 may cause decreased life span, premature aging and accelerated atherosclerosis and generalized vascular calcifications have raised the question whether FGF23 could be a new risk factor and predictor of cardiovascular (CV) disease in both renal and non-renal patient groups. Clinical studies, however, have yielded conflicting results. Some of these studies have found that serum FGF23 is independently associated with mortality and CV events in CKD patients, while others have failed to show any relationship. Furthermore, some studies have even suggested that FGF23 may have a protective role against vascular calcifications and CV disease. Thus, there is clearly a need for further research in this area, and special interest should be paid to the physiologic consequences of high FGF23/low Klotho state, which is typical for patients with CKD.
KeywordsChronic kidney disease Fibroblast growth factor 23 Klotho Cardiovascular disease Phosphatonins
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- 10.Brownstein CA, Adler F, Nelson-Williams C, Iijima J, Li P, Imura A, Nabeshima Y, Reyes Mugica M, Carpenter TO, Lifton RP (2008) A translocation causing increased alpha-Klotho level results in hypophosphatemic rickets and hyperparathyroidism. PNAS 105(9):3455–3460PubMedCentralPubMedCrossRefGoogle Scholar
- 12.Parker BD, Schurgers LJ, Brandenburg VM, Christenson RH, Vermeer C, Ketteler M et al (2010) The associations of fibroblast growth factor 23 and uncarboxylated matrix Gla protein with mortality in coronary artery disease: the Heart and Soul Study. Ann Intern Med 152(10):640–648PubMedCentralPubMedCrossRefGoogle Scholar
- 25.Desjardins L, Liabeuf S, Renard C, Lenglet A, Lemke HD, Choukroun G, Drueke TB, Massy ZA (2012) European uremic toxin (EUTox) Work Group. FGF23 is independently associated with vascular calcification but not bone mineral density in patients at various CKD stages. Osteoporos Int 23(7):2017–2025PubMedCrossRefGoogle Scholar
- 26.Schoppet M, Hofbauer LC, Brinskelle-Schmal N, Varennes A, Goudable J, Richard M, Hawa G, Chapurlat R, Szulc P (2012) Serum level of the phosphaturic factor FGF23 is associated with abdominal aortic calcification in men: the STRAMBO study. J Clin Endocrinol Metab 97(4):E575–E583PubMedCrossRefGoogle Scholar