Abstract Body: Background and Purpose
Chronic kidney disease (CKD) is associated with an increased risk of stroke and worse outcomes, yet it is often asymptomatic, with an estimated 90% of individuals unaware they have CKD until its later stages. Due to the functional and anatomical similarities of the kidney and brain microvasculature, the effects of early-stage CKD on brain health warrant further investigation. This study aimed to explore the association between estimated glomerular filtration rate (eGFR), a measure of how well the kidneys filter toxins and waste from the blood, and white matter hyperintensity (WMH), an MRI biomarker of cerebral small vessel disease linked to stroke and vascular cognitive impairment.

Methods
We performed a cross-sectional post-hoc analysis of the Atherosclerosis Risk in Communities (ARIC) cohort at study visit 7 (2018-2019), including participants with WMH measured on MRI and eGFR estimated by the CKD-EPI. While eGFR had a standard distribution and did not require transformation, WMH was right-skewed so we standardized it to total intracranial volume and created a z-score for analysis (Figure 1).

Results
We included 661 individuals (mean age 81.1±4.7, 56.6% female, 22.1% Black) with a mean WMH burden of 20.0±16.8 mL. In a linear regression model adjusted for age, sex, race, hypertension, diabetes, prior stroke, current smoking, current alcohol use, systolic blood pressure, and APOE genotype, lower eGFR was significantly associated with higher WMH (β = -0.008; 95% CI -0.013, -0.003; p < 0.001) (Figure 2). Sensitivity analysis using the same adjustments but predicting the top tertile of WMH in a logistic regression and using a categorical approach to eGFR (<30, 30-60, 60-90, >90) confirmed the results of our primary analysis (Figure 3).

Discussion
We found a significant independent association between impaired kidney function and increased WMH burden, even in the early stages of CKD. These findings emphasize the importance of early CKD detection and management to preserve brain health. Future research should investigate the bidirectionality of this relationship, particularly in the context of acute ischemic injury, focusing on the shared mechanisms of renal and neurovascular dysfunction to develop more effective prevention and therapeutic strategies aimed at reducing the burden of disease in our aging population.