Abstract: SA-PO963
Pathophysiology of CKD-Left Ventricular Diastolic Dysfunction: Role of Renal TNF-α and IL-6 Inflammatory Signaling
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 their actual pathophysiological connection remains to be fully elucidated. We developed a translational swine model that recapitulates human CKD and left ventricular diastolic dysfunction (CKD-LVDD). We hypothesized that increased pro-inflammatory cytokine signaling of renal origin imposes cardiac structural and functional abnormalities in swine CKD-LVDD
Methods
CKD-LVDD pigs (n=6 each) were studied for 14 weeks, after inhibition of renal inflammatory signaling (IRIS) achieved by a single intra-renal administration of a biopolymer fused peptide inhibitor of NF-κB (SynB1-ELP-p50i) 8 weeks earlier. Untreated CKD-LVDD and Normal pigs served as controls (n=6 each). Using a specific pig Luminex, circulating levels (inferior vena cava blood, IVC) of inflammatory cytokines were measured. Tumor necrosis factor (TNF)-α and interleukin (IL)-6 levels were distinctly elevated, confirmed by (ELISA), also measured in renal vein (RV) and coronary sinus (CS) blood, and their renal (RV-IVC) and cardiac (CS-IVC) gradients quantified. Cardiac morphology, function (echocardiography), and fibrosis were also quantified.
Results
TNF-α and IL-6 levels were higher in CKD-LVDD (A), paired with a positive renal and a negative cardiac gradient (B), and increased cardiac protein, but not gene, expression levels (C). IRIS improved TNF-α and IL-6 renal and cardiac gradients (B), decreased their cardiac protein expression (C), and ameliorated cardiac fibrosis and diastolic dysfunction (D).
Conclusion
Our study supports a crosstalk between the kidney and the heart in CKD, suggesting that inflammatory signaling of renal origin (partly led by TNF-α and IL-6) may impose cardiac abnormalities towards development of LVDD in CKD.
Funding
- NIDDK Support