3, 4 In addition to glomerular lesions, tubulointerstitial lesions contribute significantly to the decline in renal function in human diabetic nephropathy.The decline in renal function is associated with both glomerulosclerosis and tubulointerstitial fibrosis. The histopathological features of diabetic nephropathy in humans include glomerular hypertrophy, a thickening of the glomerular basement membrane, and mesangial matrix expansion, including the formation of glomerular nodular lesions known as Kimmelstiel-Wilson nodules. 2 Clinically, albuminuria is the hallmark biomarker for the diagnosis of diabetic nephropathy, and it is also used to stage diabetic nephropathy. In humans, diabetic nephropathy manifests as a clinical syndrome consisting of albuminuria, a progressive decline in renal function, and an increased risk of developing cardiovascular disease. Therefore, a novel and more beneficial treatment to suppress diabetic nephropathy has to be developed. 2 Some patients with advanced diabetic nephropathy rapidly progress to ESRD, despite having received adequate multifactorial treatment. 1 Multifactorial management, including diet therapy and glycemic, blood pressure (BP), and lipid control, is recommended for diabetic nephropathy. Among the vascular complications of diabetes, diabetic nephropathy develops in 40% of patients and remains the leading cause of end-stage renal disease (ESRD) worldwide. Long-term diabetes results in vascular changes and dysfunction, and complications of diabetes are the major causes of morbidity and mortality in diabetic patients. The prevalence of diabetes mellitus has been increasing worldwide in recent years. Keywords: diabetic nephropathy, rodent model, albuminuria, mesangial matrix expansion, tubulointerstitial fibrosis In this review, we focus on rodent models of diabetes and discuss the utility and limitations of these models for the study of diabetic nephropathy. Therefore, the validation of an animal model reproducing human diabetic nephropathy will significantly facilitate our understanding of the underlying genetic mechanisms that contribute to the development of diabetic nephropathy. Furthermore, the genetic background and strain of each mouse model result in differences in susceptibility to diabetic nephropathy with albuminuria and the development of glomerular and tubulointerstitial lesions. However, the currently available rodent models of diabetes can be useful in the study of diabetic nephropathy by increasing our understanding of the features of each diabetic rodent model. A rodent model that strongly exhibits all these features of human diabetic nephropathy has not yet been developed. An animal model of diabetic nephropathy should exhibit progressive albuminuria and a decrease in renal function, as well as the characteristic histological changes in the glomeruli and the tubulointerstitial lesions that are observed in cases of human diabetic nephropathy. In addition, db/db mice, KK- Ay mice, Zucker diabetic fatty rats, Wistar fatty rats, Otsuka Long-Evans Tokushima Fatty rats and Goto-Kakizaki rats serve as rodent models of type 2 diabetes. Akita diabetic mice that have an Ins2+/ C96Y mutation and OVE26 mice that overexpress calmodulin in pancreatic β-cells serve as a genetic model of type 1 diabetes. Streptozotocin (STZ)-induced diabetic animals are widely used as a model of type 1 diabetes. Rodent models are useful for elucidating the pathogenesis of diseases and testing novel therapies, and many type 1 and type 2 diabetic rodent models have been established for the study of diabetes and diabetic complications. Therefore, novel therapies for the suppression of diabetic nephropathy must be developed. Munehiro Kitada, 1,2 Yoshio Ogura, 2 Daisuke Koya 1,2ġDivision of Anticipatory Molecular Food Science and Technology, Medical Research Institute, 2Department of Diabetology and Endocrinology, Kanazawa Medical University, Uchinada, Ishikawa, JapanĪbstract: Diabetic nephropathy is the most common cause of end-stage renal disease.
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