New insights into the FGF23-Klotho axis

• Published in: Seminars in nephrology Vol. 34; no. 6; p. 586
• Main Authors: Olauson, Hannes, Vervloet, Marc G, Cozzolino, Mario, Massy, Ziad A, Ureña Torres, Pablo, Larsson, Tobias E
• Format: Journal Article
• Language: English
• Published: United States 01.11.2014
• Subjects: Animals; Biomarkers - blood; Fibroblast Growth Factors - genetics; Fibroblast Growth Factors - metabolism; Gene Expression Regulation; Glucuronidase - deficiency; Glucuronidase - genetics; Glucuronidase - metabolism; Humans; Hyperparathyroidism, Secondary - etiology; Hyperparathyroidism, Secondary - metabolism; Phosphates - metabolism; Renal Insufficiency, Chronic - complications; Renal Insufficiency, Chronic - metabolism; parathyroid hormone; chronic kidney disease; Fibroblast growth factor-23; calcium; FGF-23; vitamin D; phosphate
• ISSN: 1558-4488
• DOI: 10.1016/j.semnephrol.2014.09.005

Abnormal mineral metabolism is a hallmark in patients with advanced chronic kidney disease (CKD). Hyperphosphatemia, and the homeostatic mechanisms controlling phosphate metabolism, have received particular attention over the past decade. The phosphate-regulating hormone fibroblast growth factor-23 (FGF23) was discovered through studies of rare hypophosphatemic disorders, whereas Klotho, which subsequently turned out to be a co-receptor for FGF23, was identified in a mouse model showing hyperphosphatemia and multiple aging-like traits. The FGF23-Klotho endocrine axis is a pivotal regulator of mineral metabolism. In CKD, early onset of Klotho deficiency contributes to renal FGF23 resistance and a maladaptive increase in circulating FGF23. FGF23 is an early biomarker of renal injury and increased FGF23 predicts adverse clinical outcomes, in particular cardiovascular disease. A paradigm of FGF23 excess and Klotho deficiency is proposed, in which FGF23 preferentially stimulates left ventricular hypertrophy, and loss of Klotho augments fibrosis, endothelial dysfunction, and vascular calcification. The clinical benefit of FGF23 and Klotho measurements remain uncertain, nevertheless, the FGF23-Klotho axis is a solid candidate for a novel diagnostic and therapeutic target in CKD.