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Abstract: FR-OR47

Cytokines of Kidney Origin Are Retained in the Heart and Induce Cardiac Injury in CKD: A Renal-Cardio Axis

Session Information

Category: Pathology and Lab Medicine

  • 1600 Pathology and Lab Medicine

Authors

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

Chronic kidney disease (CKD) is a major contributor to heart failure (HF), but the mechanisms underpinning CKD-induced HF remain to be fully elucidated. We hypothesize that inflammatory signaling from the kidney drives the development of cardiac injury in CKD.

Methods

CKD was induced in 4 pigs (bilateral renovascular disease and dyslipidemia) and observed for 14 weeks. Normal pigs served as controls. Renal hemodynamics (RBF, GFR) were quantified by multi-detector CT, and cardiac morphology and function by echocardiography. Renal vein, coronary sinus, and systemic blood was collected to quantify renal and cardiac gradients of TNF-α and IL-6. In a biomimetic heart culture system, pig heart slices were exposed to plasma from CKD or normal pigs and contractile/relaxation kinetics and sarcoplasmic-reticulum Ca+2 dynamics were investigated.

Results

Loss of renal function in CKD was accompanied by positive renal (renal release) and negative cardiac (cardiac retention) cytokine gradients, left ventricular (LV) hypertrophy, diastolic dysfunction (E/A, E/e’ ratio) and abnormal LV strain. Cardiomyocytes exposed to CKD plasma showed impaired contractility and speed of relaxation, and altered Ca+2 cycling, which improved after TNF-α and IL-6 neutralization (Figure).

Conclusion

This study supports a link between TNF-α/IL-6 inflammatory signaling from the kidney in causing cardiac dysfunction in CKD. Cardiac impairment in vivo was mirrored by altered cardiomyocytes kinetics and Ca+2 cycling after exposure to CKD plasma in vitro, supporting an inflammatory renal-cardio axis in CKD-to-HF pathophysiology.

Funding

  • Other NIH Support