NDT Advance Access originally published online on September 27, 2005
Nephrology Dialysis Transplantation 2005 20(12):2661-2669; doi:10.1093/ndt/gfi096
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In a type 2 diabetic nephropathy rat model, the improvement of obesity by a low calorie diet reduces oxidative/carbonyl stress and prevents diabetic nephropathy
1 Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, Tokyo, 2 Institute of Medical Sciences and Division of Nephrology, Hypertension and Metabolism, Tokai University School of Medicine, Kanagawa, 3 Department of Anatomy and Internal Medicine, Fujita Health University School of Medicine, Japan, 4 Department of Medical Education and Informatics, Tokai University School of Medicine, Kanagawa and 5 Service de Nephrologie, Universite Catholique de Louvain, Brussels, Belgium
Correspondence and offprint requests to: Toshio Miyata, Institute of Medical Sciences and Division of Nephrology, Hypertension and Metabolism, Bohseidai, Isehara, Kanagawa 259-1193, Japan. Email: t-miyata{at}is.icc.u-tokai.ac.jp
Background. The present study has been undertaken to unravel the critical factors involved in the progression of diabetic nephropathy (DN).
Methods. A unique type 2 diabetic rat model with a wide range of metabolic derangements and hypertension has been utilized, the spontaneously hypertensive/NIH-corpulent rat SHR/NDmcr-cp(cp/cp). It develops histologically evident glomerular injury and tubulointerstitial damage, including mesangial activation, podocyte injury, and inflammatory cell infiltration in the tubulointerstitium.
Results. A low calorie diet for 22 weeks significantly improves obesity, proteinuria and renal morphological alterations. The correction of renal injury is independent of blood pressure control. Obesity correction, although partial, normalizes the renal content of pentosidine taken as a marker of oxidative stress and advanced glycation end products (AGEs). This occurs despite the fact that, in this model, improvement of glucose control and hyperlipidaemia is limited. Proteinuria and body weight are highly correlated with renal pentosidine content, while proteinuria and body weight are also correlated with each other. Diabetic renal injury is thus inhibited by a low calorie diet with an attendant reduction of oxidative stress and AGE formation, despite sustained hypertension.
Conclusion. The present findings suggest a direct role of obesity in the generation of a localized oxidative stress and AGE formation, directly responsible for DN.
Keywords: advanced glycation end product; multiple risk factor intervention; pentosidine; proteinuria; renoprotection
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