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Vitamin D and Klotho in Chronic Kidney Disease

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Abstract

Klotho, originally identified as an aging suppressor, forms a complex with the fibroblast growth factor (FGF) receptor and functions as an obligatory co-receptor for FGF23, a bone-derived hormone that regulates phosphate and vitamin D metabolism. The identification and characterization of the klotho-FGF23 axis has considerably advanced our understanding of chronic kidney disease-mineral and bone disorder (CKD-MBD). By acting as a co-factor for FGFR in FGF23 signaling, klotho plays a central role in the pathogenesis of disturbances of phosphate and vitamin D metabolism in CKD. Klotho also exists as a soluble circulating protein, which is produced by cleavage of the extracellular region. Although the detailed mechanism remains to be determined, soluble klotho has been shown to possess multiple functions. Accumulating data suggest that both transmembrane and soluble form of klotho is deficient in patients with CKD and such klotho deficiency contributes to the pathogenesis of secondary hyperparathyroidism, vascular calcification, left ventricular hypertrophy, and worsening of kidney injury. In this chapter, we present recent insights into the role of the klotho-FGF23 axis in the altered metabolism of phosphate and vitamin D in CKD. We also discuss the reported multifunctional roles of soluble klotho and their potential involvement in the pathophysiology of CKD-MBD.

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Authors and Affiliations

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

    Hirotaka Komaba MD, PhD

  2. Department of Oral Medicine, Infection & Immunity, Harvard School of Dental Medicine, Boston, MA, USA

    Beate Lanske MD

Authors
  1. Hirotaka Komaba MD, PhD
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  2. Beate Lanske MD
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Correspondence to Hirotaka Komaba MD, PhD .

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Editors and Affiliations

  1. Ramsay-Générale de Santé, Clinique du Landy, Saint Ouen, France

    Pablo A. Ureña Torres

  2. San Paolo Hospital, DiSS University of Milan, Milan, Italy

    Mario Cozzolino

  3. VU University Medical Center, Amsterdam, The Netherlands

    Marc G. Vervloet

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Komaba, H., Lanske, B. (2016). Vitamin D and Klotho in Chronic Kidney Disease. In: Ureña Torres, P., Cozzolino, M., Vervloet, M. (eds) Vitamin D in Chronic Kidney Disease. Springer, Cham. https://doi.org/10.1007/978-3-319-32507-1_9

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  • DOI: https://doi.org/10.1007/978-3-319-32507-1_9

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