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Updated: Jul 6, 2025
Assessment of Kidney Function in Mouse Models of Glomerular Disease
Published on: June 30, 2018
SGLT2 inhibitor improves kidney function and morphology by regulating renal metabolism in mice with diabetic kidney
Chunru Yang1, Cheng Xiao1, Xiaojun Zhai1
1Department of Endocrinology, Key Laboratory of Endocrinology National Health Commission, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China.
Background:
Diabetic kidney disease (DKD) is a secondary complication of diabetes mellitus and a leading cause of chronic kidney disease.
Aim:
To investigate the impact of long-term canagliflozin treatment on DKD and elucidate its underlying mechanism.
Methods:
DKD model was established using high-fat diet and streptozotocin in male C57BL/6J mice (n = 30). Mice were divided into five groups and treated for 12 weeks. 1) normal control mice, 2) DKD model, 3) mice treated low-dose of canagliflozin, 4) high-dose of canagliflozin and 5) β-hydroxybutyrate. Mice kidney morphology and function were evaluated, and a metabolomics analysis was performed.
Results:
Canagliflozin treatment reduced blood creatinine and urine nitrogen levels and improved systemic insulin sensitivity and glucose tolerance in diabetic mice. Additionally, a decrease in histological lesions including collagen and lipid deposition in the kidneys was observed. β-hydroxybutyrate treatment did not yield a comparable outcome. The metabolomics analysis revealed that canagliflozin induced alterations in amino acid metabolism profiles in the renal tissue of diabetic mice.
Conclusion:
Canagliflozin protects the kidneys of diabetic mice by increasing the levels of essential amino acids, promoting mitochondrial homeostasis, mitigating oxidative stress, and stimulating the amino acid-dependent tricarboxylic acid cycle.
Insights
Canagliflozin treatment improved kidney function and reduced damage in diabetic mice. This drug enhances essential amino acid levels and supports cellular energy processes, offering a protective effect against diabetic kidney disease.
Area of Science:
- Nephrology
- Endocrinology
- Pharmacology
Background:
- Diabetic kidney disease (DKD) is a major complication of diabetes mellitus.
- DKD is a leading cause of chronic kidney disease globally.
Purpose of the Study:
- To evaluate the long-term effects of canagliflozin on diabetic kidney disease.
- To understand the mechanisms behind canagliflozin's action in DKD.
Main Methods:
- A diabetic kidney disease mouse model was created using a high-fat diet and streptozotocin.
- Mice received varying doses of canagliflozin or β-hydroxybutyrate for 12 weeks.
- Kidney function, morphology, and metabolic profiles were analyzed.
Main Results:
- Canagliflozin treatment lowered creatinine and urea nitrogen levels, improving insulin sensitivity and glucose tolerance.
- Histological analysis showed reduced collagen and lipid deposition in kidneys.
- Metabolomics revealed canagliflozin altered amino acid metabolism in renal tissue.
Conclusions:
- Canagliflozin demonstrates protective effects on kidneys in a diabetic mouse model.
- The drug increases essential amino acids, promotes mitochondrial health, and reduces oxidative stress.
- Canagliflozin stimulates the amino acid-dependent tricarboxylic acid cycle for kidney protection.
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