Kidney Week

Abstract: SA-PO319

Ezetimibe Protects from Renal Dysfunction in a Mouse Model of Alport Syndrome

Session Information

• Cellular Crosstalk in Glomerular Diseases - II
  October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1201 Glomerular Diseases: Fibrosis and Extracellular Matrix

Authors

• Molina David, Judith T., 1Katz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida. , Miami, Florida, United States

Judith T. Molina David,

• Kim, Jin Ju, 1Katz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida. , Miami, Florida, United States

Jin Ju Kim,

• Varona Santos, Javier T., 1Katz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida. , Miami, Florida, United States

Javier T. Varona Santos,

• Merscher, Sandra M., 1Katz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida. , Miami, Florida, United States

Sandra M. Merscher,

• Fornoni, Alessia, 1Katz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida. , Miami, Florida, United States

Alessia Fornoni,

Background

Alport Syndrome (AS) is characterized by renal disease inevitably progressing to end-stage kidney disease (ESKD), and no treatment strategies are currently available. We have recently discovered an important contribution of renal parenchyma lipid accumulation to ESKD in mice affected by AS. We hypothesized that treatment with the lipid-lowering compound ezetimibe (EZ), which targets the cholesterol transport protein Nieman Pick C1-like 1 protein and has been shown to modulate fatty acid uptake in other organs, can prevent renal lipid accumulation and podocyte injury in an experimental mouse model of AS thus improving renal function.

Methods

EZ was administered for 4 weeks by oral gavage at 5 mg/kg to 4-week-old knockout (KO) and wildtype (WT) mice. All mice were sacrificed at 8 weeks of age. The following four groups of mice were analyzed: WT, WT + EZ, KO and KO + EZ.

Results

We detected a significant decrease in the albumin-to-creatinine ratio (ACR) in KO mice treated with EZ when compared to untreated KO mice (p<0.01). Additionally, a decrease of BUN and serum creatinine levels was observed (p<0.05). EZ treatment of KO mice also resulted in a significant reduction in the body weight loss observed during disease progression (p<0.05). Furthermore, EZ normalized renal lipid metabolism as indicated by decreased total kidney cortex triglyceride content in EZ treated KO mice compared to untreated mice (p<0.05).

Conclusion

Based on these results, we conclude that EZ improves renal function in experimental AS and could represent a new repurposing strategy for the treatment of affected patients.

Funding

• Private Foundation Support