Kidney Week

Abstract: TH-PO1012

Evaluation of the SGLT2 Inhibitor Dapagliflozin as an Alternative Treatment of Kidney Impairment in a 5/6 Nephrectomy Model Associated with Obesity

Session Information

• CKD: Epidemiology, Risk Factors, and Prevention - 1
  October 24, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

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, Sao Paulo, São Paulo, Brazil

Desiree Rita Denelle Bernardo, MS, MSc

• Canale, Daniele, Universidade de Sao Paulo Faculdade de Medicina, Sao Paulo, São Paulo, Brazil

Daniele Canale, PhD

• Nascimento, Mariana Moura, Universidade de Sao Paulo Faculdade de Medicina, Sao Paulo, São Paulo, Brazil

Mariana Moura Nascimento, MSc

• Shimizu, Maria HM, Universidade de Sao Paulo Faculdade de Medicina, Sao Paulo, São Paulo, Brazil

Maria HM Shimizu, PhD

• Seguro, Antonio C., Universidade de Sao Paulo Faculdade de Medicina, Sao Paulo, São Paulo, Brazil

Antonio C. Seguro, MD, PhD

• de Braganca, Ana Carolina, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, São Paulo, Brazil

Ana Carolina de Braganca, PhD

• Volpini, Rildo A., Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, São Paulo, Brazil

Rildo A. Volpini, PhD

Background

Chronic kidney disease is a global health burden, characterized by functional and structural renal changes as decreased GFR, inflammation and fibrosis. Obesity is a chronic disease directly related to diabetes mellitus and hypertension, the main disorders responsible for the progression to end-stage kidney disease. Lately, the alternative use of SGLT2 inhibitors has been offering new perspectives for the treatment of kidney diseases, regardless their glucosuric effects. We evaluated the effects of dapagliflozin (DAPA) as an alternative treatment on renal impairment in an obesity-associated 5/6 nephrectomy (Nx) model.

Methods

We followed male wistar rats during a 100-day protocol. On day 40, all the rats were submitted to Nx surgery and followed up until the end of the protocol. The animals were divided into four groups according to the diet: standard (N); hyperlipidic (N+H); standard+DAPA (N+D); and hyperlipidic+DAPA (N+H+D). DAPA (50 mg/kg diet) was offered from the 1st day after Nx surgery. We evaluated anthropometric data, biochemical parameters, GFR, renal protein expression of SGLT1 and GLUT2, as well as renal tissue levels of SGLT2, TGF-β, collagen 3 (COL-3) and MCP-1 by ELISA.

Results

N+H animals presented a lower GFR, increased anthropometrical and metabolic parameters, and enhanced renal tissue levels of TGF-β, COL-3 and MCP-1. N+H+D showed improved renal function, metabolic parameters, and a restoration of plasma glucose levels. Most importantly, treatment with dapagliflozin prevented the renal expression of TGF-β, COL-3 and MCP-1 in this obesity-associated Nx model. The results are described in Figure 1 (Table 1).

Conclusion

The use of dapagliflozin prevented the renal fibrosis formation and inflamation observed in our 5/6 nephrectomy model associated with obesity. Financial support: FAPESP 2022/07409-0, 2023/06387-6.

Funding

• Government Support – Non-U.S.