Opposite effects of diabetes on nephrotoxic and ischemic acute tubular necrosis.
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 less than 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 less than 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.
Wald
H
H
Nephrology and Hypertension Services, Hadassah University Hospital, Jerusalem, Israel.
Markowitz
H
H
Zevin
S
S
Popovtzer
M M
MM
D058186:Acute Kidney Injury / Q000150:complications*; D000818:Animals; D002712:Chlorides; D002857:Chromium / Q000032:analysis; D017608:Chromium Compounds; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D003928:Diabetic Nephropathies / Q000150:complications*; D004195:Disease Models, Animal; D007511:Ischemia; D007668:Kidney / Q000098:blood supply / Q000201:enzymology; D007683:Kidney Tubular Necrosis, Acute / Q000150:complications*; D008297:Male; D008627:Mercuric Chloride; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000032:analysis
D002712:Chlorides; D017608:Chromium Compounds; D002857:Chromium; D008627:Mercuric Chloride; C017133:chromous chloride; D000254:Sodium-Potassium-Exchanging ATPase