Abstract: TH-PO1171
Characterization of Renal Protection by SGLT2 Inhibitor in the Adenine Nephropathy Model
Session Information
- CKD: Mechanisms, AKI, and Beyond - 1
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2303 CKD (Non-Dialysis): Mechanisms
Authors
- Jagarlapudi, Srinath, Pfizer Global Research and Development, Cambridge, Massachusetts, United States
- Keenan, Rose Ann, Pfizer Global Research and Development, Cambridge, Massachusetts, United States
- Sun, Zhongyuan, Pfizer Global Research and Development, Cambridge, Massachusetts, United States
- Culver, Jeffrey A., Pfizer Global Research and Development, Cambridge, Massachusetts, United States
- Romoli, Simone, Pfizer Global Research and Development, Cambridge, Massachusetts, United States
- Swanson, Tyler, Pfizer Global Research and Development, Cambridge, Massachusetts, United States
- Feliers, Denis, Pfizer Global Research and Development, Cambridge, Massachusetts, United States
Group or Team Name
- Cardio-Renal Team-IMRU.
Background
SGLT2 inhibition protects renal function in diabetic and non-diabetic kidney disease. Here we tested its effect on adenine nephropathy, a model of rapidly progressing chronic kidney disease.
Methods
Adenine (0.15%)-fed mice were treated with SGLT2 inhibitor dapagliflozin (30 mg/kg, once a day) for 6 weeks. Renal function was assessed with the transdermal glomerular filtration rate technique. Proteomics and metabolomics were performed in isolated kidney cortex.
Results
Dapagliflozin prevented decline in renal function in adenine-fed mice. Renal proteomics revealed that dapa preserved energy metabolism and prevented inflammation and fibrosis in adenine-fed mice. Despite a 700-fold increase in urinary glucose excretion in dapa-treated mice, plasma glucose was unchanged. We hypothesized that increased glucose production compensated for the urinary losses. Gluconeogenesis occurs in the renal proximal tubules, using glutamine as a substrate. Renal cortex metabolomics and proteomics showed that glycolysis was increased in adenine-fed mice and that SGLT2 inhibition caused a switch to gluconeogenesis in these mice.
Conclusion
SGLT2 inhibition is renoprotective in a model of rapidly progressing kidney disease, accompanied by massive glucosuria and a switch from glucose utilization to production by the kidney. This study suggests that renal gluconeogenesis contributes to the maintenance of normoglycemia during SGLT2 inhibition.
Funding
- Commercial Support – Pfizer Inc