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Abstract: SA-PO1138

Mitigation of Kidney Fibrosis and Inflammation with Dapagliflozin Treatment in Obese Rats Under 5/6 Nephrectomy

Session Information

Category: CKD (Non-Dialysis)

  • 2301 CKD (Non-Dialysis): Epidemiology, Risk Factors, and Prevention

Authors

  • Bernardo, Desiree Rita Denelle, Universidade de Sao Paulo Faculdade de Medicina, São Paulo, SP, Brazil
  • Canale, Daniele, Universidade de Sao Paulo Faculdade de Medicina, São Paulo, SP, Brazil
  • Nascimento, Mariana Moura, Universidade de Sao Paulo Faculdade de Medicina, São Paulo, SP, Brazil
  • Seguro, Antonio C., Universidade de Sao Paulo Faculdade de Medicina, São Paulo, SP, Brazil
  • Shimizu, Maria HM, Universidade de Sao Paulo Faculdade de Medicina, São Paulo, SP, Brazil
  • de Braganca, Ana Carolina, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, São Paulo, SP, Brazil
  • Volpini, Rildo A., Universidade de Sao Paulo Faculdade de Medicina de Ribeirao Preto, Ribeirao Preto, SP, Brazil
Background

Obesity is a chronic disease related directly and indirectly to the progression of chronic kidney disease (CKD). Lately, sodium glucose co-transporter 2 (SGLT2) inhibitors, initially developed as glucose lowering agents, have been offering new perspectives for the treatment of kidney diseases. Thus, we hypothesized that dapagliflozin could mitigate inflammatory cell infiltration and interstitial fibrosis in an obesity-associated 5/6 nephrectomy (Nx) model.

Methods

Male Wistar rats (8 weeks old) were followed during a 100-day protocol and submitted to Nx surgery on day 40. The animals were randomly allocated to four groups according to the diet: standard (N); hyperlipidic (N+H); standard+dapagliflozin (N+D); and hyperlipidic+dapagliflozin (N+H+D). Dapagliflozin (50 mg/kg diet) treatment was administered daily after Nx surgery. Kidney tissues analysis were evaluated by ELISA, Multiplex assays and molecular techniques.

Results

The expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, MCP-1), and pro-fibrotic markers (TGF-β1, EGF, VEGF and Col-3) were significantly increased in the N+H group. In addition, we noted a higher expression of Glut2, Sglt2 and leptin in the N+H group when compared with N and N+D groups. In contrast, dapagliflozin treatment was capable to mitigate the levels of these factors, and to elevate the expression of Glut2 and Sglt1 in the N+H+D rats. The data are described in Table 1.

Conclusion

Our data indicate that treatment with dapagliflozin exerts a protective effect on obesity-associated kidney disease progression. Financial support: São Paulo Research Foundation (FAPESP) - Grants # 2022/07409-0, 2022/05519-3, 2023/06387-6, 2024/09066-9.

Funding

  • Government Support – Non-U.S.

Digital Object Identifier (DOI)