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The role of FGF23 in CKD—with or without Klotho

Nature Reviews Nephrology volume 8, pages 484–490 (2012)Cite this article

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Abstract

During the past few years, fibroblast growth factor 23 (FGF23) has emerged as a central player of disordered mineral metabolism in patients with chronic kidney disease (CKD). The physiological actions of FGF23 are to promote phosphaturia, decrease production of 1,25-dihydroxyvitamin D and suppress secretion of parathyroid hormone mediated through FGF receptors and the co-receptor Klotho. Recent epidemiological studies demonstrate strong associations between elevated FGF23 levels in patients with CKD and poor clinical outcomes. In patients with end-stage renal disease, markedly increased levels of FGF23 fail to exert Klotho-dependent effects owing to the absence of a functioning kidney and downregulation of the parathyroid complex of Klotho and FGF receptor 1. In this setting, FGF23 may exert a toxic effect on the cardiovascular system in a Klotho-independent manner. Future research should examine whether treatment to attenuate the pathogenic action of FGF23 provides survival benefits in patients with CKD.

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Figure 1: Synthesis, secretion, and structure of FGF23.
Figure 2: Klotho-dependent and Klotho-independent effects of FGF23 in ESRD.

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  1. Division of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine, 143 Shimo-Kasuya, Isehara, 259-1193, Japan

    Hirotaka Komaba & Masafumi Fukagawa

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Both authors contributed equally to discussion of content for the article, researching data to include in the manuscript and reviewing and editing of the manuscript before submission.

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Correspondence to Masafumi Fukagawa.

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H. Komaba has received speakers bureau honoraria from Bayer Yakuhin, Chugai Pharmaceutical and Kyowa Hakko Kirin. M. Fukagawa has received speakers bureau honoraria and grant/research support from Bayer Yakuhin, Chugai Pharmaceutical and Kyowa Hakko Kirin.

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Komaba, H., Fukagawa, M. The role of FGF23 in CKD—with or without Klotho. Nat Rev Nephrol 8, 484–490 (2012). https://doi.org/10.1038/nrneph.2012.116

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