Opposite Effects of Diabetes on Nephrotoxic and Ischemic Acute Tubular Necrosis

Abstract

Abstract

The effect of streptozotocin-induced diabetes mellitus on two different models of acute tubular necrosis (ATN), was studied: (i) the nephrotoxic model of HgCl₂-induced ATN and (ii) the ischemic model of renal artery clamping for 60 min. Induction of ATN with HgCl₂ in normal rats decreased CrCl from 0.67 ± 0.05 to 0.1 ± 0.019 ml/min (P < 0.001) after 24 hr, and it deteriorated further to 0.03 ± 0.013 ml/min after 48 hr; whereas, in the diabetic rats, HgCl₂ decreased CrCl from 0.98 ± 0.11 only to 0.31 ± 0.037 ml/min (P < 0.0001), but CrCl recovered to 0.50 ± 0.08 ml/min after 48 hr.

Bilateral clamping of renal arteries for 60 min in control and diabetic rats extremely decreased CrCl in both groups. Twenty-four hours after clamping, two of nine rats from the diabetic group died, whereas none from the control group died. Forty-eight hours after clamping, all nine rats from the diabetic group died, whereas only two rats from the control group died, and in the four surviving rats CrCl recovered slightly. Our study shows that streptozotocin-induced diabetes could not confer a general protection against ATN. It was protective against a nephrotoxic insult but aggravated the ischemic insult. An attempt to reconcile these discrepant effects is made in the Discussion.