The FGF23 and Klotho system beyond mineral metabolism

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Abstract
FGF23 is a bone-derived hormone that acts primarily on the kidney to induce phosphaturia and suppress synthesis of 1,25-dihydroxyvitamin D3. The unique feature of FGF23 is that it requires Klotho as an obligate co-receptor. The FGF23–Klotho system has emerged as an endocrine axis indispensable for maintaining phosphate homeostasis. Mineral and bone disorders associated with chronic kidney disease (CKD-MBD) can be viewed as a series of events triggered by a compensatory response of the FGF23–Klotho system to excess phosphate intake relative to the residual nephron number. Furthermore, the fact that disruption of the FGF23–Klotho system causes phosphate retention and a syndrome resembling aging in mammals has led to the notion that phosphate accelerates aging. The aging-like pathology caused by phosphate, or phosphatopathy, may be unique to the higher organisms having the Klotho gene and provides new insights into the molecular mechanism of aging in humans.
Funding Information
  • Japan Society for the Promotion of Science (KAKENHI Grant Number 16H05302, 16K15470)
  • Japan Agency for Medical Research and Development
  • Vehicle Racing Commemorative Foundation
  • Takeda Science Foundation
  • Salt Science Research Foundation
  • National Institute of Diabetes and Digestive and Kidney Diseases

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