Polycystin dysfunction and cardiac electrical abnormalities in ADPKD

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is one of the most common inherited kidney disorders characterized by the progressive formation of renal cysts. It is a systemic disease with significant extra-renal manifestations. Among these, cardiac electrical abnormalities are increasingly recognized as clinically important yet underappreciated contributors to cardiovascular morbidity and mortality. Beyond cyst formation, pathogenic variants in PKD1 or PKD2, which encode polycystin-1 (PC1) and polycystin-2 (PC2), respectively, interfere with calcium homeostasis, mechanotransduction, and mitochondrial function in both kidney and heart tissues. These molecular changes trigger a cascade of pathological events, including RAAS activation, TGF-driven fibrosis, and oxidative stress, leading to structural and electrical remodeling of the heart. These alterations contribute to cardiac electrical remodeling, manifesting clinically as QT interval and corrected QT (QT/QTc) prolongation, left ventricular hypertrophy, atrial fibrillation, ventricular arrhythmias, and other electrocardiographic abnormalities. Despite growing evidence, cardiac electrical abnormalities in ADPKD remain understudied in clinical practice. Early detection of subclinical cardiovascular abnormalities may be facilitated by electrocardiographic monitoring, cardiac imaging, and complementary biomarker assessment. Additionally, findings from iPSC-derived cardiomyocyte models support the translational potential of personalized drug-screening platforms. This review summarizes current evidence linking polycystin dysfunction to cardiac electrical abnormalities in ADPKD by integrating molecular mechanisms with experimental and clinical findings. It also highlights the need for integrated cardio-renal approaches to improve cardiovascular surveillance, risk stratification, and future therapeutic development in ADPKD.