*Purpose: End stage renal disease (ESRD) is associated with accumulation of uremic metabolites and poor cognitive performance. Alterations in brain metabolites are associated with cognitive impairment in several disease states. We examined whether the brain metabolites were altered in ESRD and whether they normalize post- kidney transplant (KT).

*Methods: We analyzed brain metabolites pre- and 12 weeks post- KT. We used magnetic resonance spectroscopic imaging (MRS) at 3 Tesla (Skyra, Siemens) to measure N-acetylaspartate (NAA), choline (Cho), creatine (Cr), myo-inositol (mI), and glutamate and glutamine (Glx) in a single slice of brain superior to the lateral ventricles. Brain metabolite signals were quantified using LCModel and reported as ratios to creatine for normalization. Comparisons of metabolite concentrations between pre- and post-KT, and ESRD and controls concentrations were made using a paired t-test.

*Results: MRS data from 11 healthy controls (age 54 ± 7, 5/11 men, 10/11 Caucasians) and 18 patients with ESRD (age 51 ± 11, 13 men, 17 Caucasians) were compared. Figure 1 shows the metabolite concentrations in controls, pre-KT and post-KT patients (*: P< 0.05 for pre-KT vs. controls; #: P< 0.05 pre-KT vs. post-KT). The mI/Cr ratio was elevated pre-KT when compared to healthy controls (P= 0.03) and decreased by 7% post-KT (P =0.008). In addition, Cho/Cr ratio was numerically higher in pre-KT ESRD and decreased by 10% post-KT (P <0.001). There was no difference in metabolites between controls and post-KT patients. There were no tissue composition (gray and white matter) differences between the analyzed brain regions.

*Conclusions: Kidney disease is associated with specific metabolic disturbances in the brain that normalize after KT. These improvements may account for improvement in cerebrovascular health and cognition function post-transplant.

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