Related Experiment Video
Updated: Jul 21, 2026
A Large Animal Model for Acute Kidney Injury by Temporary Bilateral Renal Artery Occlusion
Published on: February 2, 2021
Opposite effects of diabetes on nephrotoxic and ischemic acute tubular necrosis
1Nephrology and Hypertension Services, Hadassah University Hospital, Jerusalem, Israel.
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 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.
Insights
Diabetes mellitus did not universally protect against acute tubular necrosis (ATN). While it offered protection against nephrotoxic ATN, it worsened outcomes in ischemic ATN models.
Area of Science:
- Nephrology
- Diabetology
- Pathophysiology
Background:
- Diabetes mellitus is a complex metabolic disorder with potential systemic effects.
- Acute tubular necrosis (ATN) is a significant cause of acute kidney injury.
- The impact of diabetes on ATN pathogenesis requires further elucidation.
Purpose of the Study:
- To investigate the effect of streptozotocin-induced diabetes mellitus on two distinct models of acute tubular necrosis (ATN).
- To compare the outcomes of nephrotoxic (HgCl2) and ischemic (renal artery clamping) ATN in diabetic versus non-diabetic rats.
Main Methods:
- Streptozotocin was used to induce diabetes mellitus in rats.
- Two models of ATN were employed: HgCl2-induced nephrotoxicity and 60-minute renal artery ischemia.
- Renal function was assessed by measuring creatinine clearance (CrCl) at 24 and 48 hours post-insult.
Main Results:
- In the HgCl2 model, diabetic rats showed less severe reduction in CrCl and partial recovery at 48 hours compared to controls.
- In the ischemic model, diabetic rats exhibited higher mortality rates and more severe CrCl reduction than control rats.
- Diabetes aggravated the ischemic insult, leading to poorer outcomes and increased mortality.
Conclusions:
- Streptozotocin-induced diabetes does not provide general protection against ATN.
- Diabetes confers protection against nephrotoxic ATN but exacerbates ischemic ATN.
- The differential effects of diabetes on ATN subtypes warrant further investigation into underlying mechanisms.
More Related Videos
Related Concept Videos
01:10Nephrons
01:29Acute Kidney Injury II: Pathophysiology
01:30Acute Kidney Injury IV: Diagnostic Studies and Prevention
01:20Acute Kidney Injury V: Interprofessional Care
01:22Acute Kidney Injury VI: Nursing Management
01:28Diabetic Nephropathy