It remains unclear whether the difference between the estimated glomerular filtration rate based on cystatin C and creatinine (eGFRdiff) is associated with cerebral small vessel disease (CSVD). We investigated the correlation of eGFRdiff with SCVD and further evaluated the mediating role of blood pressure.

This prospective cohort study included 35,590 neurologically healthy participants at baseline (2006 to 2010) from the UK Biobank. eGFRdiff is divided into two indicators: absolute difference (eGFRabdiff) and ratio (eGFRrediff) based on the calculation between cystatin C and creatinine. CSVD was assessed by calculating white matter hyperintensity volume (WMHV) from T2-FLAIR brain MRI scans (conducted between 2014 and 2021), with values normalized to intracranial volume and log-transformed. Multiple linear regression models and mediation analysis was used to evaluate the associations of eGFRdiff with WMHV.

Participants with negative eGFRabdiff had higher WMHV (β = 0.07, 95 % confidence interval [CL] = 0.04 ∼ 0.10), while participants with positive eGFRabdiff had smaller WMHV (β = -0.05, 95 %CL = -0.09 ∼ -0.02), compared to midrange eGFRabdiff group. Meanwhile, participants with eGFRrediff ≤ 0.7 had higher WMHV compared with participants with eGFRrediff > 0.7 (β = 0.08, 95 %CL = 0.01∼ 0.15) .In addition, hypertension mediated the associations between eGFRdiff and WMHV (12.6 % ∼13.2 %).

eGFRdiff was independently associated with WMHV. Our findings suggested that monitoring eGFRdiff has potential benefits in identifying the burden of CSVD in the general population in future.