Causal Links Between Renal Function and Cardiac Structure, Function, and Disease Risk.

Abstract

Chronic kidney disease (CKD) increases the risk of adverse cardiovascular outcomes. However, the causal relationships between renal function and cardiovascular diseases (CVD) remain incompletely understood. This study aimed to determine the causal relationships between genetic susceptibility to impaired renal function and the risk of CVD endpoints, as well as cardiac structure and function detectable by cardiac magnetic resonance imaging (CMR). Bidirectional Mendelian randomization (MR) analyses were conducted using summary-level data from genome-wide association studies. The exposures were blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR), urine albumin-to-creatinine ratio (UACR), and CKD. The outcomes included atrial fibrillation, coronary artery disease (CAD), myocardial infarction, heart failure, stroke, and various CMR parameters. Sensitivity analyses, multivariable MR adjusting for cardiometabolic traits, and replication in the FinnGen cohort were performed. Elevated BUN levels (OR 1.505; 95% CI 1.077 to 2.103; P = 0.017) were causally associated with increased CAD risk, but this relationship was attenuated after adjusting for cardiometabolic traits. Increased UACR was causally linked to higher risks of CAD (OR 1.260; 95% CI 1.042 to 1.523; P = 0.017), myocardial infarction (OR 1.424; 95% CI 1.137 to 1.783; P = 0.002), and stroke (OR 1.182; 95% CI 1.012 to 1.379; P = 0.035), with the association for stroke remaining significant after multivariable adjustment. Reduced eGFR was causally related to decreases in ascending aorta diameter, proximal pulmonary artery diameter, right atrial size, left ventricular stroke volume, and right ventricular volumes, even after accounting for potential confounders. CKD was causally associated with a reduced pulmonary artery-to-aorta ratio and proximal pulmonary artery diameter. This comprehensive MR study establishes causal roles of genetic susceptibility to impaired renal function influencing cardiovascular outcomes and cardiac structure.