Abstract: PO2231
A Novel Model of CKD and Heart Failure with Preserved Ejection Fraction
Session Information
- Pathology and Lab Medicine: Basic
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
Category: Pathology and Lab Medicine
- 1601 Pathology and Lab Medicine: Basic
Authors
- Chade, Alejandro R., University of Mississippi Medical Center, Jackson, Mississippi, United States
- Williams, Maxx, University of Mississippi Medical Center, Jackson, Mississippi, United States
- Engel, Jason E., University of Mississippi Medical Center, Jackson, Mississippi, United States
- Hall, Michael, University of Mississippi Medical Center, Jackson, Mississippi, United States
Background
Chronic kidney disease (CKD) has high cardiovascular mortality. We developed a model of CKD that shows major pathological features: low GFR (+/- 60 ml/min), renal inflammation, fibrosis, microvascular disease, and hypertension. We aim to define the cardiac phenotype of the model and, if present, the pathological traits involved
Methods
CKD was induced in 6 pigs (bilateral renovascular disease and dyslipidemia) and observed for 14 weeks. Renal hemodynamics (RBF, GFR) were quantified by multi-detector C, cardiac morphology and function by echocardiography, and mean arterial pressure (MAP) by telemetry. Blood was collected to measure circulating inflammatory cytokines (TNF-α, MCP-1), markers of inflammation (C-reactive protein), and biomarkers of heart failure (ANP, BNP, NT-proBNP). Pigs were then euthanized and kidneys and hearts collected for ex vivo studies. Normal pigs were used as time-matched controls
Results
Loss of renal function was accompanied by left ventricular hypertrophy, left atrial dilatation, diastolic dysfunction (E/A ratio) with preserved ejection fraction (pEF), elevated ANP, BNP, and NT-proBNP, and hypertension (MAP of 131.2 mm/Hg, p<0.05 vs. normal). CKD also increased renal (but not cardiac) mRNA expression of TNF-α, MCP-1, and IL-6, accompanied by increased circulating inflammatory cytokines (Figure)
Conclusion
CKD leads to cardiac abnormalities that meet the criteria of heart failure with pEF (HFpEF). Our data suggest that hypertension and inflammatory mediators (possibly from kidney origin) target the heart and may contribute to HFpEF pathophysiology. HFpEF associates with CKD in about 50% of cases and has no specific treatment. Our study offers a new experimental platform to increase our understanding of CKD-HFpEF and to test new treatments in a translational fashion
Funding
- Other NIH Support