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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:1910.)
© 2007 American Heart Association, Inc.

Vascular Biology

Exacerbation of Albuminuria and Renal Fibrosis in Subtotal Renal Ablation Model of Adiponectin-Knockout Mice

Koji Ohashi; Hirotsugu Iwatani; Shinji Kihara; Yasuhiko Nakagawa; Noriyuki Komura; Koichi Fujita; Norikazu Maeda; Makoto Nishida; Fumie Katsube; Iichiro Shimomura; Takahito Ito; Tohru Funahashi

From the Departments of Metabolic Medicine (K.O., S.K., Y.N., N.K., K.F., N.M., M.N., F.K., I.S., T.F.) and Nephrology (H.I., T.I.), Graduate School of Medicine, Osaka University, Japan.

Correspondence to Shinji Kihara, MD, PhD, Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. E-mail kihara{at}imed2.med.osaka-u.ac.jp

Objective— Obesity is recognized increasingly as a major risk factor for kidney disease. We reported previously that plasma adiponectin levels were decreased in obesity, and that adiponectin had defensive properties against type 2 diabetes and hypertension. In this study, we investigated the role of adiponectin for kidney disease in a subtotal nephrectomized mouse model.

Methods and Results— Subtotal (5/6) nephrectomy was performed in adiponectin-knockout (APN-KO) and wild-type (WT) mice. The procedure resulted in significant accumulation of adiponectin in glomeruli and interstitium in the remnant kidney. Urinary albumin excretion, glomerular hypertrophy, and tubulointerstitial fibrosis were significantly worse in APN-KO mice compared with WT mice. Intraglomerular macrophage infiltration and mRNA levels of vascular cell adhesion molecule (VCAM)-1, MCP-1, tumor necrosis factor (TNF)-, transforming growth factor (TGF)-β1, collagen type I/III, and NADPH oxidase components were significantly increased in KO mice compared with WT mice. Treatment of APN-KO mice with adenovirus-mediated adiponectin resulted in amelioration of albuminuria, glomerular hypertrophy, and tubulointerstitial fibrosis and reduced the elevated levels of VCAM-1, MCP-1, TNF-, TGF-β1, collagen type I/III, and NADPH oxidase components mRNAs to the same levels as those in WT mice.

Conclusions— Adiponectin accumulates to the injured kidney, and prevents glomerular and tubulointerstitial injury through modulating inflammation and oxidative stress.

Obesity is a major risk factor for kidney disease. Adiponectin has many protective properties for obesity-related diseases. In this study, we investigated the role of adiponectin for kidney disease in a nephrectomized mouse model. Adiponectin accumulates to the injured kidney and prevents kidney injury through modulating inflammation and oxidative stress.

Key Words: adiponectin • obesity • subtotal nephrectomy • inflammation • oxidative stress

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