A short story of Klotho and FGF23: a deuce of dark side or the savior?
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.
Division of Nephrology, Department of Medicine, Akdeniz University Medical School, Antalya, 07070, Turkey, ersoy@akdeniz.edu.tr.
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D002318:Cardiovascular Diseases / Q000209:etiology / Q000401:mortality; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000502:physiology*; D005966:Glucuronidase / Q000502:physiology*; D006801:Humans; D000090265:Klotho Proteins; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000209:etiology / Q000503:physiopathology
C000717427:FGF23 protein, human; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D005966:Glucuronidase; D000090265:Klotho Proteins