Background and purpose: The CHA2DS2-VASc score has immense prognostic value in patients with embolic stroke of undetermined source (ESUS). We aimed to determine the usefulness of advanced renal dysfunction and its addition to the CHA2DS2-VASc score in improving predictive accuracy. Methods: In total, 3775 ESUS patients were enrolled from a nationwide hospital-based prospective study. Advanced renal dysfunction was defined as estimated glomerular filtration rate <30 ml/min per 1.73 m2 or patients under dialysis. Clinical outcomes included recurrent stroke and 1-year all-cause mortality. Poor functional outcome was defined as a modified Rankin Scale >2 at first-, third-, and sixth-month post-stroke. The renal (R)-CHA2DS2-VASc score was derived by including advanced renal dysfunction in the CHA2DS2-VASc score. Risk stratification improvement after including advanced renal dysfunction was assessed using C statistic, integrated discrimination improvement (IDI), and category-free net reclassification index (NRI). Results: After adjusting for confounding factors and CHA2DS2-VASc score, advanced renal dysfunction showed significant associations with all-cause mortality (HR: 2.88, 95% CI: 1.92–4.34) and poor functional outcome at third- (OR: 2.69, 95% CI: 1.47–4.94) and sixth-month post-stroke (OR: 2.67, 95% CI: 1.47–4.83). IDI and NRI showed that incorporating advanced renal dysfunction significantly improved risk discrimination over the original CHA2DS2-VASc score. R-CHA2DS2-VASc score ≥2 increased risk by 1.94-fold (95% CI: 1.15–3.27) for all-cause mortality, and ≥4 increased risk by 1.62-fold (95% CI: 1.05–2.50) of poor functional outcome at third-month post-stroke and by 1.81-fold (95% CI: 1.19–2.75) at sixth-month post-stroke. Conclusions: Advanced renal dysfunction was significantly associated with clinical and functional outcomes in ESUS patients and may improve prognostic impact of the CHA2DS2-VASc score.
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