Associations of microalbuminuria with brain atrophy and white matter hyperintensities in hypertensive sibships

Background: Because of similarities between brain and kidney microvascular disease, there may be a relationship between measures of renal microvascular disease and brain structural changes in middle aged or elderly individuals. Objective: To determine whether the urine albumin/creatinine ratio (UACR), a measure of renal microvascular disease, is associated with brain atrophy and white matter hyperintensities. Methods: As part of a larger study of the genetics of hypertension, we performed brain imaging and assessed microalbuminuria and other vascular risk factors including diabetes, hypertension, hyperlipidemia and hyperhomocysteinemia in 1253 individuals from hypertensive sibships (age mean 63.8 years, range 50 to 91; 65% women; 49% African-American; 78% hypertensive). Semi-automated quantitative measurements of brain atrophy (BA) ventricular volume, and white matter hyperintensities (WMH) were carried out on the brain MR scans. Results: In logistic regression models, elevated UACR was associated with greater BA (odds ratio (OR) = 1.70 (95% CI 1.14, 2.54) and burden of WMH (OR = 2.06 (95% CI 1.37, 3.10) after controlling for demographic factors, blood glucose, hypertension severity, duration of smoking and serum homocysteine. In contrast to elevated UACR, the associations with elevated creatinine or reduced glomerular filtration rate and WMH were not significant in the fully adjusted models. Conclusions: In this cohort with an overrepresentation of hypertensives, elevated UACR was independently associated with both brain atrophy and white matter hyperintensities. Brain volume loss and WMH burden might represent expressions of microvascular disease that share common mechanisms with nephrosclerosis.