Normalization of Cerebral Blood Flow, Neurochemicals, and White Matter Integrity after Kidney Transplantation
Authors: Lepping Rebecca J. , Montgomery Robert N. , Sharma Palash , Mahnken Jonathan D. , Vidoni Eric D. , Choi In-Young , Sarnak Mark J. , Brooks William M. , Burns Jeffrey M. , Gupta Aditi 
Published: October 2020

Significance Statement
Kidney disease is accompanied by structural and physiologic brain abnormalities and increased risk of dementia and stroke. Because RRT with dialysis does not normalize these brain abnormalities, the authors evaluated the possible benefit of kidney transplantation. Using magnetic resonance imaging methods to measure brain abnormalities before and after kidney transplantation, they demonstrated that this intervention normalizes cerebral blood flow, neurochemical concentrations, and white matter integrity. They also found that these changes persist beyond the initial post-transplantation period and thus, cannot be attributed to periprocedural interventions, such as steroids. Their findings suggest that brain abnormalities in kidney disease may be reversible. Further studies are needed to understand the mechanisms underlying these brain abnormalities and to explore interventions to prevent and mitigate them in patients who cannot undergo kidney transplantation.

Background
CKD is associated with abnormalities in cerebral blood flow, cerebral neurochemical concentrations, and white matter integrity. Each of these is associated with adverse clinical consequences in the non-CKD population, which may explain the high prevalence of dementia and stroke in ESKD. Because cognition improves after kidney transplantation, comparing these brain abnormalities before and after kidney transplantation may identify potential reversibility in ESKD-associated brain abnormalities.

Methods
In this study of patients with ESKD and age-matched healthy controls, we used arterial spin labeling to assess the effects of kidney transplantation on cerebral blood flow and magnetic resonance spectroscopic imaging to measure cerebral neurochemical concentrations (N-acetylaspartate, choline, glutamate, glutamine, myo-inositol, and total creatine). We also assessed 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 magnetic resonance imaging measurements before, 3 months after, and 12 months after transplantation and compared these findings with those of healthy controls.

Results
Study participants included 29 patients with ESKD and 19 controls; 22 patients completed post-transplant magnetic resonance imaging. Cerebral blood flow, which was higher in patients pretransplant compared with controls (P=0.003), decreased post-transplant (P<0.001) to values in controls. Concentrations of neurochemicals choline and myo-inositol that were higher pretransplant compared with controls (P=0.001 and P<0.001, respectively) also normalized post-transplant (P<0.001 and P<0.001, respectively). FA increased (P=0.001) and MD decreased (P<0.001) post-transplant.

Conclusions
Certain brain abnormalities in CKD are reversible and normalize with kidney transplantation. 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.

Clinical Trial registry name and registration number:
Cognitive Impairment and Imaging Correlates in End Stage Renal Disease, NCT01883349