Associations between structural and functional changes to the kidney in diabetic humans and mice

Type 1 and Type 2 diabetic patients are at high risk of developing diabetic nephropathy (DN). Renal functional decline is gradual and there is high variability between patients, though the reason for the variability is unknown. Enough diabetic patients progress to end stage renal disease to make diabetes the leading cause of renal failure. The first symptoms of DN do not appear for years or decades after the onset of diabetes. During and after the asymptomatic period structural changes develop in the diabetic kidney. Typically, but not always, the first symptom of DN is albuminuria. Loss of renal filtration rate develops later. This review examines the structural abnormalities of diabetic kidneys that are associated with and possibly the basis for advancing albuminuria and declining GFR. Mouse models of diabetes and genetic manipulations of these models have become central to research into mechanisms underlying DN. This article also looks at the value of these mouse models to understanding human DN as well as potential pitfalls in translating the mouse results to humans.