Abstract: FR-PO0156
Advanced Mouse Models of Diabetic Kidney Disease (DKD) in Type 2 Diabetes
Session Information
- Diabetic Kidney Disease: Metabolic, Mitochondrial, and Inflammatory Mechanisms
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Cardiovascular-Kidney-Metabolic Health
- 601 Cardiovascular-Kidney-Metabolic Health: Basic
Authors
- Luo, Kaiming, WuXi AppTec, Shanghai, China
- Li, Dan, WuXi AppTec, Shanghai, China
- Qi, Hao, WuXi AppTec, Shanghai, China
Background
Globally, diabetic kidney disease (DKD) is a major long-term complication of type 1 and type 2 diabetes, affecting 20%–40% of diabetic patients, among whom 40%–50% eventually progress to end-stage renal disease. Research on mid-to-late-stage DKD is hindered by an extremely long phenotypic onset period, typically over 40 weeks. There is therefore an urgent need to develop appropriate animal models that recapitulate the mid-to-late stages of diabetes within a shorter timeframe (<20 weeks). To support the development of novel therapeutic strategies for halting DKD progression, we established two mouse models mimicking the mid-to-late stages of type 2 diabetes.
Methods
Model 1#: Male db/db mice (8–10 weeks old) were injected with Renin-encoding AAV two weeks prior to unilateral nephrectomy (UNx). Renin adeno-associated virus was delivered to induce hypertension and thereby accelerate DKD progression in db/db mice.
Model 2#: Global eNOS knockout was generated on a db/db diabetic background. eNOS deficiency in db/db mice exacerbates endothelial dysfunction and glomerular hyperfiltration, further accelerating the onset and progression of diabetic renal injury.
In-life and terminal evaluations included blood and urinary biochemistry, blood glucose, blood pressure, glomerular filtration rate (GFR), and pathological examinations via H&E, PAS and IHC staining.
Results
In Model 1#, mice exhibited elevated urinary ACR and KIM-1 levels, as well as increased serum creatinine and BUN. Blood pressure was elevated as expected. The Renin-AAV UNx db/db model showed markedly increased histological scores, accompanied by renal interstitial inflammatory infiltration, tubular damage, interstitial fibrosis and glomerulosclerosis, which recapitulate the key pathological features of late-stage DKD.
Consistently, Model 2# (BKS-db-eNOS KO mice) displayed increased urinary ACR and blood pressure. GFR was significantly decreased in BKS-db-eNOS KO mice, indicating impaired renal function. H&E and PAS staining revealed aggravated tubular injury, tubular atrophy and dilation, interstitial fibrosis, and a higher glomerulosclerotic index.
Conclusion
Either the Renin-AAV UNx db/db model or the BKS-db-eNOS KO model is well-suited for investigating mid-to-late diabetic nephropathy, and provides reliable platforms for preclinical studies on late-stage DKD.