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Decreased renal α-Klotho expression in early diabetic nephropathy in humans and mice and its possible role in urinary calcium excretion.
MedLine Citation:
PMID:  22217880     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.Kidney International advance online publication, 4 January 2012; doi:10.1038/ki.2011.423.
Authors:
Osamu Asai; Kimihiko Nakatani; Tomohiro Tanaka; Hirokazu Sakan; Akihiro Imura; Shuhei Yoshimoto; Ken-Ichi Samejima; Yukinari Yamaguchi; Masaru Matsui; Yasuhiro Akai; Noboru Konishi; Masayuki Iwano; Yoichi Nabeshima; Yoshihiko Saito
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-1-04
Journal Detail:
Title:  Kidney international     Volume:  -     ISSN:  1523-1755     ISO Abbreviation:  -     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-1-5     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0323470     Medline TA:  Kidney Int     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
First Department of Internal Medicine, Nara Medical University, Kashihara, Japan.
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