Decreased renal α-Klotho expression in early diabetic nephropathy in humans and mice and its possible role in urinary calcium excretion

被引：147

作者：

Asai, Osamu ^{[1
]}

Nakatani, Kimihiko ^{[1
,2
]}

Tanaka, Tomohiro ^{[3
]}

Sakan, Hirokazu ^{[1
]}

Imura, Akihiro ^{[3
]}

Yoshimoto, Shuhei ^{[1
]}

Samejima, Ken-ichi ^{[1
]}

Yamaguchi, Yukinari ^{[1
]}

Matsui, Masaru ^{[1
]}

Akai, Yasuhiro ^{[1
]}

Konishi, Noboru ^{[2
]}

Iwano, Masayuki ^{[1
,4
]}

Nabeshima, Yoichi ^{[3
]}

Saito, Yoshihiko ^{[1
,5
]}

机构：

[1] Nara Med Univ, Dept Internal Med 1, Kashihara, Nara 6348522, Japan

[2] Nara Med Univ, Dept Pathol, Kashihara, Nara 6348522, Japan

[3] Kyoto Univ, Grad Sch Med, Dept Pathol & Tumor Biol, Kyoto, Japan

[4] Univ Fukui, Fac Med Sci, Dept Gen Med, Div Nephrol, Fukui, Japan

[5] Nara Med Univ, Dept Regulatory Med Blood Pressure, Kashihara, Nara 6348522, Japan

来源：

KIDNEY INTERNATIONAL | 2012年 / 81卷 / 06期

关键词：

diabetic nephropathy; hypercalciuria; hypoxia; CA2+ CHANNELS TRPV5; STREPTOZOTOCIN; MELLITUS; RAT; HYPERCALCIURIA; AMELIORATION; CAPILLARIES; ASSOCIATION; GLOMERULI; TRANSPORT;

D O I：

10.1038/ki.2011.423

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

Hypercalciuria is one of the early manifestations of diabetic nephropathy. We explored here the role of alpha-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 alpha-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 alpha-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 alpha-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 alpha-Klotho knockout mice in comparison with wild-type mice, each with STZ-induced diabetic nephropathy. Thus, alpha-Klotho expression was decreased in distal convoluted tubules in diabetic nephropathy in humans and mice. Renal loss of a-Klotho may affect urinary calcium excretion in early diabetic nephropathy. Kidney International (2012) 81, 539-547; doi: 10.1038/ki.2011.423; published online 4 January 2012

引用

页码：539 / 547

页数：9

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