Normalization of Cerebral Blood Flow, Neurochemicals, and White Matter Integrity After Kidney Transplantation

Background: Chronic kidney disease (CKD) is associated with abnormalities in cerebral blood flow (CBF), cerebral neurochemical concentrations and white matter integrity, each of which are associated with adverse clinical consequences in the non-CKD population, and may explain the high prevalence of dementia and stroke in end stage kidney disease (ESKD). Since cognition improves after kidney transplantation (KT), we examined these brain abnormalities pre-to post-KT to identify potential reversibility in ESKD-associated brain abnormalities. Methods: We measured the effects of KT on CBF assessed by arterial spin labeling, cerebral neurochemical concentrations (N-acetylaspartate, choline, glutamate and glutamine, myo-inositol and total creatine) measured by magnetic resonance spectroscopic imaging, and white matter integrity measured by fractional anisotropy (FA) and mean diffusivity (MD) with diffusion tensor imaging. We used a linear mixed model analysis to compare longitudinal, repeated brain MRI measurements pre-KT, and 3 months and 12 months post-KT, and also compared findings with healthy controls. Results: 29 ESKD patients and 19 age-matched healthy controls participated in the study. 22 patients underwent post-KT MRI. CBF, which was higher pre-KT than in controls (p=0.003), decreased post-KT (p<0.0001) to values in controls. KT also normalized concentrations of osmotic neurochemicals choline (p<0.0001) and myo-inositol (p=0.0003) that were higher pre-KT compared to controls. Post-KT, FA increased (p=0.001) and MD decreased (p=0.0001). Conclusions: Brain abnormalities in CKD are reversible and normalize with KT. Further studies are needed to understand the mechanisms underlying these brain abnormalities and to explore interventions to mitigate them even in patients who cannot be transplanted.