Chronic Kidney Disease Induces Proarrhythmic Remodeling.

Area of Science:

• Nephrology
• Cardiology
• Molecular Biology

Background:

• Patients with chronic kidney disease (CKD) face elevated risks of cardiac arrhythmias and sudden cardiac death.
• The underlying mechanisms linking CKD to cardiac dysfunction remain incompletely understood.

Purpose of the Study:

• To investigate the intricate relationship between chronic kidney disease progression and cardiac remodeling.
• To elucidate the structural, electrophysiological, and molecular changes in the heart associated with CKD.

Main Methods:

• Utilized murine models of CKD induced by adenine-rich diet.
• Performed electrocardiography, optical mapping with voltage-sensitive dyes, and patch-clamp electrophysiology.
• Conducted global transcriptional profiling to identify key molecular pathways involved.

Main Results:

• CKD mice exhibited significant QT prolongation and bradycardia, indicating cardiac electrical instability.
• Isolated cardiomyocytes showed altered sodium and potassium currents, contributing to prolonged action potential duration.
• Dysregulated expression of RNA-binding motif protein 3 (RBM3) and cold-inducible RNA-binding protein (CIRP) was identified.
• Female sex emerged as a protective factor against CKD progression and cardiac complications.

Conclusions:

• Novel insights into the association between CKD and proarrhythmic cardiac remodeling were established.
• Cardiac cellular stress response pathways, involving RBM3 and CIRP, are implicated in CKD-induced heart rhythm disorders.
• Targeting these stress pathways presents a promising therapeutic strategy for managing cardiac sequelae of CKD.