Abstract: FR-PO0795
Dapagliflozin with Losartan but Not Olmesartan Has Add-On Protective Effect in Experimental Alport Syndrome
Session Information
- Glomerular Diseases: Cell Homeostasis and Novel Injury Mechanisms
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Horizono, Jun, Department of Molecular Medicine, Graduate School of Pharmaceutical Science, Kumamoto University, Kumamoto, Japan
- Suico, Mary Ann, Department of Molecular Medicine, Graduate School of Pharmaceutical Science, Kumamoto University, Kumamoto, Japan
- Kaseda, Shota, Department of Molecular Medicine, Graduate School of Pharmaceutical Science, Kumamoto University, Kumamoto, Japan
- Shuto, Tsuyoshi, Department of Molecular Medicine, Graduate School of Pharmaceutical Science, Kumamoto University, Kumamoto, Japan
- Kai, Hirofumi, Department of Molecular Medicine, Graduate School of Pharmaceutical Science, Kumamoto University, Kumamoto, Japan
Background
The sodium-glucose co-transporter 2 inhibitors (SGLT2i) have been shown to slow the progression of proteinuria and reduce the risk of end-stage kidney disease in clinical trials for chronic kidney disease (CKD), including Alport syndrome. Treatment with angiotensin receptor blockers (ARBs) is recommended for CKD patients who have increased proteinuria and a low estimated glomerular filtration rate. Thus, the use of SGLT2i in combination with ARBs is expected to increase. However, which combination of ARB and SGLT2i is more effective remains controversial. In the present study, we investigated the add-on effect of the SGLT2i dapagliflozin on losartan and olmesartan in a CKD mouse model.
Methods
We administered dapagliflozin, losartan, and olmesartan singly, or the combination of dapagliflozin and each ARB via drinking water to the Alport mouse model (Col4a5-G5X), and evaluated the renal function and survival of Alport mice.
Results
Losartan and olmesartan monotherapy suppressed proteinuria in Alport mice, with the effect being more substantial for olmesartan. Dapagliflozin alone did not decrease proteinuria in Alport mice. Dapagliflozin combined with losartan suppressed proteinuria more than losartan alone, but dapagliflozin did not exhibit an add-on effect on olmesartan. Consistently, losartan and olmesartan monotherapy, but not dapagliflozin, extended the lifespan of Alport mice. Dapagliflozin with losartan imparted longer survival than losartan alone. The combination of olmesartan and dapagliflozin was comparable to that of olmesartan monotherapy. Notably, Alport mice survival in the three treatment groups - olmesartan alone, losartan and dapagliflozin, and olmesartan and dapagliflozin - were almost identical. These findings suggest that the add-on effect of dapagliflozin varies depending on the ARB, and that their combination needs careful evaluation for maximum benefit.
Conclusion
The present study demonstrated the add-on effect of dapagliflozin to losartan and the renoprotective effect of olmesartan monotherapy. Our findings highlight the need for future studies that scrutinize the clinical data on which types of RAS inhibitors are used in combination with SGLT2 inhibitors in CKD patients.