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Updated: Jun 22, 2026
A Large Animal Model for Acute Kidney Injury by Temporary Bilateral Renal Artery Occlusion
Published on: February 2, 2021
Hyperglycemic kidney damage in an animal model of prolonged critical illness
Ilse Vanhorebeek1, Jan Gunst, Björn Ellger
1Department of Intensive Care Medicine, Katholieke Universiteit Leuven, Leuven, Belgium.
Abstract:
Acute kidney injury frequently complicates critical illness and increases mortality; maintaining normoglycemia with insulin has been shown to reduce the incidence of intensive care unit (ICU)-acquired kidney injury. Here we tested the mechanisms by which this intervention might achieve its goal, using a rabbit model of burn-induced prolonged critical illness in which blood glucose and insulin were independently regulated at normal or elevated levels. Hyperglycemia caused elevated plasma creatinine and severe morphological kidney damage that correlated with elevated cortical glucose levels. Renal cortical perfusion and oxygen delivery were lower in hyperglycemic/hyperinsulinemic rabbits, compared to other groups, but this did not explain the elevated creatinine. Mitochondrial respiratory chain activities were severely reduced in the hyperglycemic groups (30-40% residual activity), and were inversely correlated with plasma creatinine and cortical glucose. These activities were much less affected by normoglycemia, and hyperinsulinemia was not directly protective. Mitochondrial damage, evident at day 3, preceded the structural injury evident at 7 days. Our study found that hyperglycemia evoked cellular glucose overload in the kidneys of critically ill rabbits, and this was associated with mitochondrial dysfunction and renal injury. Normoglycemia, independent of insulinemia, protected against this damage.
Insights
Maintaining normal blood sugar levels (normoglycemia) protects kidneys during critical illness. This study shows hyperglycemia causes kidney injury by impairing mitochondria, independent of insulin levels.
Area of Science:
- Nephrology
- Critical Care Medicine
- Mitochondrial Biology
Background:
- Acute kidney injury (AKI) is a common complication of critical illness, increasing mortality.
- Normoglycemia achieved with insulin therapy has been observed to reduce intensive care unit (ICU)-acquired AKI.
Purpose of the Study:
- To investigate the mechanisms by which normoglycemia protects against AKI in critical illness.
- To determine the role of hyperglycemia and hyperinsulinemia in renal injury.
Main Methods:
- A rabbit model of burn-induced critical illness was used.
- Blood glucose and insulin levels were independently regulated at normal or elevated levels.
- Renal function, morphology, cortical glucose, perfusion, oxygen delivery, and mitochondrial respiratory chain activities were assessed.
Main Results:
- Hyperglycemia led to elevated plasma creatinine and severe kidney damage, correlated with cortical glucose levels.
- Mitochondrial respiratory chain activities were significantly reduced in hyperglycemic groups, preceding structural kidney injury.
- Normoglycemia protected against renal injury, independent of insulin levels; hyperinsulinemia was not directly protective.
Conclusions:
- Hyperglycemia causes cellular glucose overload in the kidneys during critical illness, leading to mitochondrial dysfunction and renal injury.
- Normoglycemia, independent of insulin, is protective against AKI in this model.
- Mitochondrial dysfunction is an early event in hyperglycemia-induced kidney injury.
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