Pathogenesis and Treatment of Diabetic Nephropathy

Diabetic nephropathy is a major cause of end-stage kidney disease (ESKD) in patients with both type 1 and type 2 diabetes. Almost 30% of type 1 or 2 diabetic patients develop diabetic nephropathy despite strict blood glucose and/or blood pressure control. In human glomeruli, the expansion of diffuse mesangial matrices, exudative lesions and/or segmental nodular sclerosis are pathological characteristics of diabetic nephropathy. The spontaneous mouse model, i. e. the KK-Ay mouse, was produced through the transfer of the yellow obese gene (Ay allele) into the KK mouse. The diabetic phenotype in this mouse is more severe than that in KK mouse. In 2006, Ito et al. reported that the pathological changes in the glomeruli of KK-Ay mice were consistent with those in the early stage of human diabetic nephropathy 1) . In electron microscopy, a diffuse thickening of the glomerular basement membrane (GBM) was observed in this model mouse. Advanced glycation end products (AGEs) and the transforming growth factor-β (TGF-β) protein appeared to be localized in the glomerular mesangial matrices. The KK-Ay mouse, especially in terms of histopathological findings, is considered to be a suitable animal model for type 2 diabetic nephropathy 2) . The objective of this review is to introduce a new strategy for the treatment of type 2 diabetic nephropathy using the KK-Ay mouse.