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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.

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Acknowledgements

Funding was provided by Japan Society for the Promotion of Science (Grant Nos. 16H05302, 16K15470).

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  1. Division of Anti-aging Medicine, Center for Molecular Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan

    Makoto Kuro-o

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  1. Makoto Kuro-o
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Correspondence to Makoto Kuro-o.

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Conflict of interest

This supplement is supported by the grants from The Japanese Society for Kidney Bone Disease (JSKBD) and from the Research Meeting on Kidney and Metabolic Bone Disease.

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Kuro-o, M. The FGF23 and Klotho system beyond mineral metabolism. Clin Exp Nephrol 21 (Suppl 1), 64–69 (2017). https://doi.org/10.1007/s10157-016-1357-6

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  • DOI: https://doi.org/10.1007/s10157-016-1357-6

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