Albuminuria and Cerebral Small Vessel Disease: A Systematic Review and Meta-Analysis.

Abstract

To determine whether albuminuria, a marker of systemic endothelial dysfunction, is associated with cerebral small vessel disease (SVD). Systematic review following the Meta-analyses Of Observational Studies in Epidemiology guidelines; independent reviewers searched Pubmed/Medline and Scopus, data were extracted, studies were evaluated on quality, and random-effects models were implemented for meta-analysis. Observational studies quantifying an association between albuminuria and cerebral SVD. Adults. Magnetic resonance imaging-defined markers of cerebral SVD; white matter hyperintensities (WMHs), lacunar infarcts (LIs), cerebral microbleeds (CMBs), and enlarged perivascular spaces (EPVSs). Of 31 eligible studies comprising 23,056 participants identified, 27 were included in quantitative synthesis. Most of the studies were cross-sectional and of varying quality. On meta-analysis, albuminuria was associated with greater risk of WMHs (odds ratio (OR)=1.70, 95% confidence interval (CI)=1.43-2.01; 13,548 subjects, 2,665 cases; I2 =44%), LIs (OR=1.86, 95% CI=1.49-2.31; 12,857 subjects, 998 cases; I2 =27%), CMBs (OR=1.78, 95% CI=1.30-2.43; 7,645 subjects; 748 cases; I2 =39%), and EPVSs in the basal ganglia (OR=1.78, 95% CI=1.02-3.09; 1,388 subjects, 399 cases; I2 =37%) and centrum semiovale (OR=3.27, 95% CI=1.49-7.20; 1,146 subjects, 460 cases; I2 =66%). Sensitivity analyses for high-quality and general population studies, but also studies controlling for cardiovascular disease risk factors and renal function, confirmed the findings and resolved the moderate heterogeneity and publication bias that were evident in the overall analyses. Albuminuria is independently associated with cerebral SVD, indicating shared microvascular pathology in the kidney and the brain. The results suggest that peripheral systemic microvascular disease biomarkers could be useful in the evaluation of brain microvascular damage.