The progression of diabetes‐induced renal injury in Dahl salt‐sensitive rats

Abstract

Diabetic nephropathy (DN) is the most common cause of chronic kidney failure in the US. However, little is known about the pathogenesis of DN because the lack of an appropriate rodent model. The aim of the present study was to determine whether the induction of diabetes in Dahl salt-sensitive (SS) rats would promote similar renal abnormalities as seen in patients with DN. Nine week-old SS rats were treated with either (1) vehicle or (2) streptozotocin (STZ, 50 mg/kg, i.p.) to induce diabetes and given insulin implants (2 U/day, s.c) to maintain plasma glucose between 300–400 mg/dL. Rats were fed a low salt diet to minimize the development of hypertension. At 18 weeks of age, protein excretion increased to 338±37 mg/day in STZ treated rats versus 54±6 mg/day in vehicle treated rats. Plasma blood urea nitrogen (BUN) levels were 67% higher in the STZ group compared to the vehicle group. Transforming growth factor beta and matrix metalloproteinase-2 protein levels were significantly elevated in the kidneys of the STZ group versus that seen in the vehicle group. STZ treated rats exhibited renal histological abnormalities typical of diabetes including mesangial expansion, glomeruloslcerosis, and interstitial fibrosis. These results indicate that SS rats treated with STZ develop progressive renal injury and display renal histopathological lesions characteristic to those seen in patients with DN. NIH grants HL36279 and HL29587