Innate immune cell-mediated mechanisms of ventricular arrhythmia in chronic kidney disease

• Applicant: Dr. Frederick Sinha
• Subject Area: Cardiology, Angiology
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 581560347

Sudden cardiac death (SCD) is a major cause of mortality worldwide. Chronic kidney disease (CKD) is one of the most frequent comorbidities in cardiovascular disease and increases the likelihood of myocardial infarction (MI) followed by fatal arrhythmias dramatically. Despite known mechanisms, the link between CKD and arrhythmia remains unclear, resulting in limited treatment options and poor outcomes. Recent work from the Kumowski/Nahrendorf group (host laboratory for this fellowship) has revealed that cells of the innate immune system play a central role in cardiac electrical stability. They demonstrated that following myocardial infarction, neutrophils release inflammatory mediators that induce oxidative stress and membrane injury, thereby facilitating ventricular tachycardia. Furthermore, they showed that myocardial infarction shifts macrophage numbers from protecting, resident macrophages to proinflammatory, recruited macrophages. This shift led to arrhythmia susceptibility and increased mortality, establishing innate immune cells as key regulators of cardiac electrophysiology.CKD induces a chronic pro-inflammatory state characterized by endothelial activation, chemokine secretion, and enhanced recruitment of neutrophil and pro-inflammatory macrophage populations. We hypothesize that CKD amplifies pro-arrhythmic neutrophil activity and shifts the cardiac macrophage landscape from protective resident cells toward recruited, inflammatory macrophages. This immune dysregulation may increase electrical instability and ventricular tachyarrhythmia burden that can be aggravated by myocardial infarction. To test this hypothesis, the project will integrate CKD and MI mouse models with advanced immunophenotyping, single-cell transcriptomics, and functional cardiac analyses. By combining my expertise in renal physiology with the host laboratory’s pioneering work in cardio-immunology, this study aims to uncover fundamental pathways through which CKD drives lethal ventricular arrhythmias. This may help to identify novel immune-modulatory targets to prevent sudden cardiac death in CKD.

• DFG Programme: WBP Fellowship
• International Connection: USA
• Hosts: Dr. Nina Kumowski; Professor Dr. Matthias Nahrendorf