Abstract: TH-PO0369
Effect of SGLT2 Inhibitors on Crescentic Glomerulonephritis
Session Information
- Glomerular Diseases: Genetics to Therapeutics
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Meegoda Dewage, Tharindi, Sorbonne Universite, Paris, Île-de-France, France
- Melis, Lisa, Sorbonne Universite, Paris, Île-de-France, France
- Cohen, Camille, Assistance Publique - Hopitaux de Paris, Paris, Île-de-France, France
- Gallazzini, Morgan, Centre de Recherche sur l'Inflammation, Paris, Île-de-France, France
- El Karoui, Khalil, Assistance Publique - Hopitaux de Paris, Paris, Île-de-France, France
Group or Team Name
- Common and Rare Kidney Diseases
Background
Crescentic glomerulonephritis (CrGN) is a severe disease characterized by the development of a glomerular cell crescent due to the accumulation of parietal epithelial cells (PECs) in Bowman's space. Some subpopulations of PEC (major component of the crescent) share a protein expression profile with proximal tubular cells, including the expression of the sodium/glucose co-transporter SGLT2. Current treatments (immunosuppressants) of CrGNs do not target mechanisms related to crescent establishment, and are associated with significant side effects. Thus, we propose to study in an innovative way the impact of early treatment with SGLT2 inhibitor (iSGLT2/gliflozins) in CrGNs.
Methods
In vivo, we will use a CrGN model on C57BL/6J mice by injection of nephrotoxic serum (NTS), whether or not treated with dapagliflozin. In vitro, we will use a primary culture of murine PECs, exposed to HB-EGF (a growth factor involved in their activation), and whether or not treated with dapagliflozine. In parallel, the expression of SGLT2 on biopsies of CRGN patients was analyzed.
Results
We highlight the expression of SGLT2 in crescents on biopsies of patients with CrGN and in animals. In animals, we showed that DAPA limited the formation of crescents and the expression of PEC activation markers (CD44, CD9 and Claudine I), and improved renal function (uremia and creatinineemia). In addition, in vitro, it also limits the activation, migration and proliferation of PECs. In parallel, through a metabolomics study (in vitro), we show an increase in glycolysis pathway products in activated PECs. We hypothesized a possible role of glycolytic metabolism in our pathological activation models. As a result, we blocked the glycolysis pathway (by a glucose analogue: 2-DG), and observed a decrease of crescents in vivo, activation and migration/proliferation of in vitro PECs. These data support the hypothesis that activation of PECs is accompanied by an increase in glycolysis and the beneficial effects of iSGLT2 could potentially involve a decrease in this glycolytic signature.
Conclusion
These results suggest a beneficial role in SGLT2 inhibition in CrGNs with a potential role of the glycolysis pathway, thus opening a new perspective for the use of iSGLT2 in these diseases.
Funding
- Government Support – Non-U.S.