Phosphate and Vitamin D in Chronic Kidney Disease

Editor(s): Razzaque, M.S. (Boston, MA)
 

Parathyroid Function in Chronic Kidney Disease: Role of FGF23-Klotho Axis

Koizumi M. · Komaba H. · Fukagawa M.

Author affiliations

Division of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine, Isehara, Japan

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Razzaque MS (ed): Phosphate and Vitamin D in Chronic Kidney Disease. Contrib Nephrol. Basel, Karger, 2013, vol 180, pp 110-123
https://doi.org/10.1159/000346791

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Article / Publication Details

Published online: May 03, 2013
Cover Date: 2013

Number of Print Pages: 14
Number of Figures: 1
Number of Tables: 0

ISBN: 978-3-318-02369-5 (Print)
eISBN: 978-3-318-02370-1 (Online)

Abstract

The parathyroid gland plays a central role in the regulation of mineral metabolism. In patients with chronic kidney disease (CKD), circulating levels of parathyroid hormone (PTH) are progressively increased as kidney function declines, as a result of phosphate retention, hypocalcemia, decreased production of 1,25-dihydroxyvitamin D [1,25(OH)2D], endogenous changes within the parathyroid gland, and skeletal resistance to the actions of PTH. In addition, the identification of fibroblast growth factor 23 (FGF23) and its cofactor Klotho offers important implications for the deeper understanding of disordered mineral metabolism in CKD. In early CKD, increased FGF23 to maintain neutral phosphate balance results in suppression of renal 1,25(OH)2D production and thereby triggers the early development of secondary hyperparathyroidism. FGF23 also acts directly on the parathyroid to decrease PTH synthesis and secretion, but this effect is blunted in advanced stages of CKD, due to decreased expression of the Klotho-FGF receptor 1 complex and increased concentrations of C-terminal FGF23 that competes with full-length FGF23 for binding to the receptor complex. Recent clinical studies also reported that high levels of FGF23 are associated with morbidity and mortality as well as treatment resistance to active vitamin D, suggesting the potential of FGF23 as a novel biomarker to guide treatment of disordered phosphate metabolism in CKD. This review will discuss the pathogenesis of secondary hyperparathyroidism, particularly focusing on the emerging role of the FGF23-Klotho axis in patients with CKD.

© 2013 S. Karger AG, Basel



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Article / Publication Details

Published online: May 03, 2013
Cover Date: 2013

Number of Print Pages: 14
Number of Figures: 1
Number of Tables: 0

ISBN: 978-3-318-02369-5 (Print)
eISBN: 978-3-318-02370-1 (Online)

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