1. Decreased renal α-Klotho expression in early diabetic nephropathy in humans and mice and its possible role in urinary calcium excretion
- Author
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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, and Saito, Yoshihiko
- Subjects
hypoxia ,diabetic nephropathy ,urologic and male genital diseases ,female genital diseases and pregnancy complications ,hypercalciuria - 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., 博士（医学）・乙第1293号・平成24年5月28日, © 2012 International Society of Nephrology
- Published
- 2012