UK Biobank guideline review links higher UMOD levels to lower aortic regurgitation progression riskHigher UMOD levels linked to lower risk of needing aortic valve replacement surgery in patients with aortic regurgitation

BackgroundAortic regurgitation (AR) frequently remains asymptomatic for prolonged periods, with guideline recommendations for intervention largely guided by imaging-based assessment of left ventricular remodeling. While renal dysfunction has been linked to adverse outcomes in AR, prior studies have predominantly focused on advanced disease stages and post-interventional outcomes, with limited data on pre-interventional progression, offering limited insight into pre-interventional disease progression or biologically informed approaches to risk stratification.MethodsWe investigated renal biomarkers in individuals with AR from the UK Biobank (n = 2,493) and assessed associations with time to aortic valve replacement (AVR) using Cox proportional hazards models. Associations with cardiovascular imaging and hemodynamic phenotypes were examined via logistic regression. To place clinical findings in a biological context, we performed genome-wide colocalization analyses between AR phenotypes, blood pressure, and renal traits, followed by regulatory annotation, single-cell RNA sequencing (Kidney Cell Atlas), and phenome-wide association analyses.ResultsAmong patients with AR, higher circulating UMOD levels were independently associated with a lower risk of subsequent AVR (adjusted HR per SD 0.57, 95% CI 0.34–0.98; p = 0.041), whereas conventional renal markers (creatinine, urea, microalbumin) showed no association. UMOD levels were strongly associated with lower arterial stiffness (β = −5.32 ± 0.27; p