New Insights Into the FGF23-Klotho Axis

作者：Olauson Hannes; Vervloet Marc G; Cozzolino Mario; Massy Ziad A; Torres Pablo Urena; Larsson Tobias E^*

来源：Seminars in Nephrology, 2014, 34(6): 586-597.

DOI：10.1016/j.semnephrol.2014.09.005

• Fibroblast growth factor-23
• FGF-23
• calcium
• phosphate
• vitamin D
• parathyroid hormone
• chronic kidney disease

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.

• 出版日期2014-11