AbstractBackgroundChronic 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.MethodsWe measured the effects of KT on CBF assessed by arterial spin labeling, cerebral neurochemical concentrations (N-acetylaspartate, choline, glutamate and glutamine, myoinositol 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.Results29 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).ConclusionsBrain 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.Significance statementKidney disease is accompanied by brain structural and physiological abnormalities and increased risk of dementia and stroke. Renal replacement therapy with dialysis does not normalize these brain abnormalities. We evaluated these brain abnormalities before and after kidney transplantation and demonstrated that unlike dialysis, kidney transplantation normalizes cerebral blood flow, neurochemical concentrations and white matter integrity. These changes persist beyond initial post-transplantation period and thus cannot be attributed to peri-procedural interventions like steroids. These results indicate reversibility of brain abnormalities in kidney disease. Further studies are needed to understand the mechanisms underlying these abnormalities and explore interventions for prevention and mitigation in patients who cannot be transplanted.
Multiple Factors Involved in the Pathogenesis of White Matter Lesions
