Kidney function and microstructural integrity of brain white matter

Objective: To investigate the association of kidney function with white matter microstructural integrity. Methods: We included 2,726 participants with a mean age of 56.6 years (45% men) from the population-based Rotterdam Study. Albumin-to-creatinine ratio, and estimated glomerular filtration rate (eGFR), using serum cystatin C (eGFRcys) and creatinine (eGFRcr), were measured to evaluate kidney function. Diffusion-MRI was used to assess microstructural integrity of the normal-appearing white matter. Multiple linear regression models, adjusted for macrostructural MRI markers and cardiovascular risk factors, were used to model the association of kidney function with white matter microstructure. Results: Participants had average eGFRcr of 86.1 mL/min/1.73m², average eGFRcys of 86.2 mL/min/1.73m², and median albumin-to-creatinine ratio of 3.4 mg/g. Lower eGFRcys was associated with worse global white matter microstructural integrity, reflected as lower fractional anisotropy (standardized difference per SD: 20.053, 95% confidence interval [CI]: 20.092, 20.014) and higher mean diffusivity (0.036, 95% CI: 0.001, 0.070). Similarly, higher albumin-to-creatinine ratio was associated with lower fractional anisotropy (-0.044, 95%CI: -0.078, -0.011). There was no linear association between eGFRcr and white matter integrity. Subgroup analyses showed attenuation of the associations after excluding subjects with hypertension. The associations with global diffusion tensor imaging measures did not seem to be driven by particular tracts, but rather spread across multiple tracts in various brain regions. Conclusions: Reduced kidney function is associated with worse white matter microstructural integrity. Our findings highlight the importance for clinicians to consider concomitant macroand microstructural changes of the brain in patients with impaired kidney function.