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Please use this identifier to cite or link to this item: http://hdl.handle.net/10564/2743

Title: Reduced renal α-Klotho expression in CKD patients and its effect on renal phosphate handling and vitamin D metabolism.
Other Titles: 慢性腎臓病症例での腎臓におけるα-Klotho発現の低下とその腎臓でのリン制御とビタミンD代謝に対する影響についての検討
Authors: Sakan, Hirokazu
Nakatani, Kimihiko
Asai, Osamu
Imura, Akihiro
Tanaka, Tomohiro
Yoshimoto, Shuhei
Iwamoto, Noriyuki
Kurumatani, Norio
Iwano, Masayuki
Nabeshima, Yo-ichi
Konishi, Noboru
Saito, Yoshihiko
Issue Date: 23-Jan-2014
Publisher: Public Library of Science
Citation: PloS one Vol.9 No.1 p.e86301
Abstract: Renal α-Klotho (α-KL) plays a fundamental role as a co-receptor for fibroblast growth factor 23 (FGF23), a phosphaturic hormone and regulator of 1,25(OH)2 vitamin D3 (1,25VitD3). Disruption of FGF23-α-KL signaling is thought to be an early hallmark of chronic kidney disease (CKD) involving reduced renal α-KL expression and a reciprocal rise in serum FGF23. It remains unclear, however, whether the rise in FGF23 is related to the loss of renal α-KL. We evaluated α-KL expression in renal biopsy samples and measured levels of several parameters of mineral metabolism, as well as soluble α-KL (sKL), in serum and urinary samples from CKD patients (n = 236). We found that although renal α-KL levels were significantly reduced and serum FGF23 levels were significantly elevated in early and intermediate CKD, serum phosphate levels remained within the normal range. Multiple regression analysis showed that the increases in FGF23 were significantly associated with reduced renal function and elevated serum phosphate, but were not associated with loss of renal α-KL. Moreover, despite falling renal α-KL levels, the increase in FGF23 enhanced urinary fractional excretion of phosphate and reduced serum 1,25VitD3 levels in early and intermediate CKD, though not in advanced CKD. Serum sKL levels also fell significantly over the course of CKD, and renal α-KL was a significant independent determinant of sKL. These results demonstrate that FGF23 levels rise to compensate for renal failure-related phosphate retention in early and intermediate CKD. This enables FGF23-α-KL signaling and a neutral phosphate balance to be maintained despite the reduction in α-KL. In advanced CKD, however, renal α-KL declines further. This disrupts FGF23 signaling, and serum phosphate levels significantly increase, stimulating greater FGF23 secretion. Our results also suggest the serum sKL concentration may be a useful marker of renal α-KL expression levels.
Description: 博士(医学)・乙第1340号・平成26年7月22日
© 2014 Sakan Hirokazu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
URI: http://hdl.handle.net/10564/2743
ISSN: 19326203
Academic Degrees and number: 24601B1340
Degree-granting date: 2014-07-22
Degree name: 博士(医学)
Degree-granting institutions: 奈良県立医科大学
Appears in Collections:2014年度

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