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Abstract: SA-PO242

Effects of Non-Steroidal Mineralocorticoid Antagonist (Finerenone) in Western Diet-Induced Kidney Disease

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • Myakala, Komuraiah, Georgetown University Medical Center, Washington, District of Columbia, United States
  • de Carvalho Ribeiro, Patricia, Georgetown University Medical Center, Washington, District of Columbia, United States
  • Wang, Xiaoxin, Georgetown University Medical Center, Washington, District of Columbia, United States
  • Korolowicz, Kyle E., Georgetown University Medical Center, Washington, District of Columbia, United States
  • Rodriguez, Olga C., Georgetown University Medical Center, Washington, District of Columbia, United States
  • Albanese, Chris, Georgetown University Medical Center, Washington, District of Columbia, United States
  • Levi, Moshe, Georgetown University Medical Center, Washington, District of Columbia, United States
Background

Mineralocorticoid receptor (MR) overactivation plays a crucial role in the pathogenesis of chronic kidney disease, several cardiovascular and arterial diseases. Clinical studies demonstrated the beneficial effects of steroidal MR antagonists (MRAs) spironolactone and eplerenone on kidney disease. However, long term usage of MRAs increases the risk of hyperkalemia with reduced kidney function. We aim to test the non-steroidal MR antagonist Finerenone as a novel treatment of kidney disease in a mouse model of diet induced obesity and insulin resistance.

Methods

2-month old C57BL/6J mice fed on low fat (LF) or western diet (WD) were treated with vehicle or FINERENONE for 6-months until they were 8 months old. Food intake and body weight was measured for every week during the entire study period. At the end of the study, 24-hour urine collected and serum and tissues were harvested for further evaluation. Blood pressure also measured via tail cuff. To assess the kidney function, dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) was performed using Gadoxetate disodium (Eovist).

Results

The body weight and kidney weight were increased significantly in mice fed WD compared to LF fed mice (N=12), which were significantly reduced with Finerenone administration although the blood glucose levels did not change between all the groups. The WD fed mice exhibited significantly increased albuminuria, which was decreased with Finerenone treatment. In kidney of mice fed WD, we detected increased expression levels of pro-inflammatory cytokines MCP1 and TNFα, innate immunity pathways TLR2, STING and STAT3, and senescence marker p21. Their expression was significantly decreased with Finerenone. The DCE-MRI indicated that mice fed WD showed a more rapid and sustained uptake of Eovist in the kidney compared to mice fed LF, suggestive of reduced clearance capacity. In contrast, finerenone treatment in WD fed mice exhibited Eovist uptake and clearance rates more similar to those seen in the LF diet control mice.

Conclusion

Our data shows that administration of Finerenone exhibits renal protective role and prevent the progression of kidney disease in a mouse model of diet induced obesity and insulin resistance.

Funding

  • Commercial Support