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Please use this identifier to cite or link to this item: http://hdl.handle.net/10564/2765

Title: Decreased renal α-Klotho expression in early diabetic nephropathy in humans and mice and its possible role in urinary calcium excretion.
Other Titles: 早期糖尿病性腎症での腎臓におけるα-Klotho 発現の低下とその尿中カルシウム排世に対する役割についての検討
Authors: Asai, Osamu
Nakatani, Kimihiko
Tanaka, Tomohiro
Sakan, Hirokazu
Imura, Akihiro
Yoshimoto, Shuhei
Samejima, Ken-ichi
Yamaguchi, Yukinari
Matsui, Masaru
Akai, Yasuhiro
Konishi, Noboru
Iwano, Masayuki
Nabeshima, Yoichi
Saito, Yoshihiko
Keywords: diabetic nephropathy
hypercalciuria
hypoxia
Issue Date: Mar-2012
Publisher: Nature Publishing Group
Citation: Kidney international Vol.81 No.6 p.539-547
Abstract: Hypercalciuria is one of the early manifestations of diabetic nephropathy. We explored here the role of α-Klotho, a protein expressed predominantly in distal convoluted tubules that has a role in calcium reabsorption. We studied 31 patients with early diabetic nephropathy and compared them with 31 patients with IgA nephropathy and 7 with minimal change disease. Renal α-Klotho expression was significantly lower and urinary calcium excretion (UCa/UCr) significantly higher in diabetic nephropathy than in IgA nephropathy or minimal change disease. Multiple regression analyses indicated that α-Klotho mRNA was inversely correlated with calcium excretion. We next measured these parameters in a mouse model of streptozotocin (STZ)-induced diabetic nephropathy, characterized by glomerular hyperfiltration, as seen in early diabetic nephropathy. We also confirmed a reduction of renal α-Klotho mRNA down to almost 50% and enhanced calcium excretion in mice with STZ-induced diabetic nephropathy in comparison with nondiabetic mice. Hypercalciuria was exacerbated in heterozygous α-Klotho knockout mice in comparison with wild-type mice, each with STZ-induced diabetic nephropathy. Thus, α-Klotho expression was decreased in distal convoluted tubules in diabetic nephropathy in humans and mice. Renal loss of α-Klotho may affect urinary calcium excretion in early diabetic nephropathy.
Description: 博士(医学)・乙第1293号・平成24年5月28日
© 2012 International Society of Nephrology
URI: http://hdl.handle.net/10564/2765
ISSN: 00852538
Appears in Collections:2012年度

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