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Kidney Week

Abstract: SA-PO962

Pathophysiology and Molecular Characterization of a Novel Model of CKD and Left Ventricular Diastolic Dysfunction (CKD-LVDD Model)

Session Information

  • CKD: Pathobiology - II
    November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

  • 2203 CKD (Non-Dialysis): Mechanisms

Authors

  • Chade, Alejandro R., The University of Mississippi Medical Center, Jackson, Mississippi, United States
  • Eirin, Alfonso, Mayo Clinic Minnesota, Rochester, Minnesota, United States
Background

Chronic kidney disease (CKD) is an independent risk factor for the development of heart failure, but the underlying mechanisms remain unknown. We developed a translational swine model of CKD and left ventricular diastolic dysfunction (CKD-LVDD) that replicates human disease and showed that cardiac abnormalities associate with a marked renal release of inflammatory cytokines to the systemic circulation, suggesting a potential pathophysiological connection. We examined whether the cardiac transcriptomic landscape is altered in CKD-LVDD pigs compared to normal controls.

Methods

CKD-LVDD and normal pigs (n=6 each) were studied for 14 weeks. Cardiac morphology and function (echocardiography) and renal hemodynamics (multi-detector CT) were quantified in vivo. mRNA-sequencing studies were performed (n=3 each) and expression profiles for dysregulated (fold change >1.4 or <0.7 and p<0.05) mRNAs in CKD-LVDD pigs were functionally interpreted by gene ontology analysis. Cardiac remodeling, inflammation, calcium cycling, and mitochondrial morphology.

Results

Cardiac abnormalities in CKD-LVDD were associated to differentially expressed calcium signaling, mitochondrial, and inflammatory genes, accompanied by cardiac fibrosis, mitochondrial damage, M1 macrophage infiltration, and altered calcium cycling vs. normal controls.

Conclusion

Our integrated pathophysiology and molecular data from a translational model of disease may set the stage for future specific interventions to ameliorate the development of LVDD in CKD.

Funding

  • NIDDK Support