Supplementary Material for: Association between Kidney Function and the Burden of Cerebral Small Vessel Disease: An Updated Meta-Analysis and Systematic Review

Introduction: Due to anatomical and functional similarities in microvascular beds, the brain and kidney share distinctive susceptibilities to vascular injury and common risk factors of small vessel disease. The aim of this updated meta-analysis is to explore the association between kidney function and the burden of cerebral small vessel disease (CSVD). Methods: PubMed, EMBASE, and Cochrane Library were systematically searched for observational studies that explored the association between the indicators of kidney function and CSVD neuroimaging markers. The highest-adjusted risk estimates and their 95% confidence intervals (CIs) were aggregated using random-effect models. Results: Twelve longitudinal studies and 51 cross-sectional studies with 57,030 subjects met the inclusion criteria of systematic review, of which 52 were included in quantitative synthesis. According to the pooled results, we found that low estimated glomerular filtration rate (eGFR 2) was associated with cerebral microbleeds (odds ratio (OR) = 1.55, 95% CI = 1.26–1.90), white matter hyperintensities (OR = 1.40, 95% CI = 1.05–1.86), and lacunar infarctions (OR = 1.50, 95% CI = 1.18–1.92), but not with severe perivascular spaces (OR = 1.20, 95% CI = 0.77–1.88). Likewise, patients with proteinuria (OR = 1.75, 95% CI = 1.47–2.09) or elevated serum cystatin C (OR = 1.51, 95% CI = 1.25–1.83) also had an increased risk of CSVD. Conclusion: The association between kidney function and CSVD has been comprehensively updated through this study, that kidney insufficiency manifested as low eGFR, proteinuria, and elevated serum cystatin C was independently associated with CSVD burden