Background: End-stage renal disease (ESRD) is a disease with an aging population and a high prevalence of cognitive impairment affecting quality of life, health care costs and mortality. Structural changes in the brain with decreased white matter integrity have been observed in ESRD. Understanding the changes in cognition and associated changes in brain structure after renal transplantation can help define the mechanisms underlying cognitive impairment in ESRD. Methods: We conducted a prospective, observational cohort study in ESRD patients listed for renal transplantation and followed them post-transplantation. We assessed their cognitive function with a battery of neuropsychological tests and brain white matter integrity with diffusion tensor imaging (DTI) both before transplant and 3 months after transplant. Results: Eleven patients, aged 56.5 ± 10.7 years, completed the study. Cognitive measures of memory and executive function improved after the transplant, specifically on tests of logical memory I (p = 0.004), logical memory II (p = 0.003) and digit symbol (p < 0.0001). DTI metrics also improved post the transplant with an increase in fractional anisotropy (p = 0.01) and decrease in mean diffusivity (p = 0.004). These changes were more prominent in tracts associated with memory and executive function. Conclusions: Cognitive function, particularly memory and executive function, improve post the transplant with concurrent improvements in white matter integrity in tracts associated with memory and executive function. These data suggest that abnormalities in cognition and brain structure seen in the ESRD population are at least partially reversible.

Keywords:
Renal transplantation, End-stage renal disease, Brain magnetic resonance imaging, Brain white matter integrity, Diffusion tensor imaging, Fractional anisotropy, Cognitive impairment
1.
Murray AM, Tupper DE, Knopman DS, Gilbertson DT, Pederson SL, Li S, et al: Cognitive impairment in hemodialysis patients is common. Neurology 2006;67:216-223.
2.
Kurella M, Mapes DL, Port FK, Chertow GM: Correlates and outcomes of dementia among dialysis patients: the dialysis outcomes and practice patterns study. Nephrol Dial Transplant 2006;21:2543-2548.
3.
Drew DA, Weiner DE, Tighiouart H, Scott T, Lou K, Kantor A, et al: Cognitive function and all-cause mortality in maintenance hemodialysis patients. Am J Kidney Dis 2015;65:303-311.
4.
Ikram MA, Vernooij MW, Hofman A, Niessen WJ, van der Lugt A, Breteler MM: Kidney function is related to cerebral small vessel disease. Stroke 2008;39:55-61.
5.
Drew DA, Bhadelia R, Tighiouart H, Novak V, Scott TM, Lou KV, et al: Anatomic brain disease in hemodialysis patients: a cross-sectional study. Am J Kidney Dis 2013;61:271-278.
6.
Hsieh TJ, Chang JM, Chuang HY, Ko CH, Hsieh ML, Liu GC, et al: End-stage renal disease: in vivo diffusion-tensor imaging of silent white matter damage. Radiology 2009;252:518-525.
7.
Ozcan H, Yucel A, Avşar UZ, Cankaya E, Yucel N, Gözübüyük H, et al: Kidney transplantation is superior to hemodialysis and peritoneal dialysis in terms of cognitive function, anxiety, and depression symptoms in chronic kidney disease. Transplant Proc 2015;47:1348-1351.
8.
Voineskos AN, Rajji TK, Lobaugh NJ, Miranda D, Shenton ME, Kennedy JL, et al: Age-related decline in white matter tract integrity and cognitive performance: a DTI tractography and structural equation modeling study. Neurobiol Aging 2012;33:21-34.
9.
Chen Y, Wang A, Tang J, Wei D, Li P, Chen K, et al: Association of white matter integrity and cognitive functions in patients with subcortical silent lacunar infarcts. Stroke 2015;46:1123-1126.
10.
Zhang R, Liu K, Yang L, Zhou T, Qian S, Li B, et al: Reduced white matter integrity and cognitive deficits in maintenance hemodialysis ESRD patients: a diffusion-tensor study. Eur Radiol 2015;25:661-668.
11.
Kim HS, Park JW, Bai DS, Jeong JY, Hong JH, Son SM, et al: Diffusion tensor imaging findings in neurologically asymptomatic patients with end stage renal disease. NeuroRehabilitation 2011;29:111-116.
12.
Chen CL, Lai PH, Chou KJ, Lee PT, Chung HM, Fang HC: A preliminary report of brain edema in patients with uremia at first hemodialysis: evaluation by diffusion-weighted MR imaging. AJNR Am J Neuroradiol 2007;28:68-71.
13.
Chou MC, Hsieh TJ, Lin YL, Hsieh YT, Li WZ, Chang JM, et al: Widespread white matter alterations in patients with end-stage renal disease: a voxelwise diffusion tensor imaging study. AJNR Am J Neuroradiol 2013;34:1945-1951.
14.
Murray AM, Pederson SL, Tupper DE, Hochhalter AK, Miller WA, Li Q, et al: Acute variation in cognitive function in hemodialysis patients: a cohort study with repeated measures. Am J Kidney Dis 2007;50:270-278.
15.
Shirk SD, Mitchell MB, Shaughnessy LW, Sherman JC, Locascio JJ, Weintraub S, et al: A web-based normative calculator for the uniform data set (UDS) neuropsychological test battery. Alzheimers Res Ther 2011;3:32.
16.
Agganis BT, Weiner DE, Giang LM, Scott T, Tighiouart H, Griffith JL, et al: Depression and cognitive function in maintenance hemodialysis patients. Am J Kidney Dis 2010;56:704-712.
17.
Hedayati SS, Minhajuddin AT, Toto RD, Morris DW, Rush AJ: Validation of depression screening scales in patients with CKD. Am J Kidney Dis 2009;54:433-439.
18.
Topolski TD, LoGerfo J, Patrick DL, Williams B, Walwick J, Patrick MB: The rapid assessment of physical activity (RAPA) among older adults. Prev Chronic Dis 2006;3:A118.
19.
Carpenter PA, Just MA, Reichle ED: Working memory and executive function: evidence from neuroimaging. Curr Opin Neurobiol 2000;10:195-199.
20.
Ohtani T, Nestor PG, Bouix S, Saito Y, Hosokawa T, Kubicki M: Medial frontal white and gray matter contributions to general intelligence. PLoS One 2014;9:e112691.
21.
Kozlovskiy SA, Vartanov AV, Pyasik MM, Nikonova EY: Functional role of corpus callosum regions in human memory functioning. Int J Psychophysiol 2012;85:396-397.
22.
Grieve SM, Williams LM, Paul RH, Clark CR, Gordon E: Cognitive aging, executive function, and fractional anisotropy: a diffusion tensor MR imaging study. AJNR Am J Neuroradiol 2007;28:226-235.
23.
Kinnunen KM, Greenwood R, Powell JH, Leech R, Hawkins PC, Bonnelle V, et al: White matter damage and cognitive impairment after traumatic brain injury. Brain 2011;134(pt 2):449-463.
24.
Newcombe VF, Correia MM, Ledig C, Abate MG, Outtrim JG, Chatfield D, et al: Dynamic changes in white matter abnormalities correlate with late improvement and deterioration following TBI: a diffusion tensor imaging study. Neurorehabil Neural Repair 2016;30:49-62.
25.
Radić J, Ljutić D, Radić M, Kovačić V, Dodig-Ćurković K, Šain M: Kidney transplantation improves cognitive and psychomotor functions in adult hemodialysis patients. Am J Nephrol 2011;34:399-406.
26.
Kramer L, Madl C, Stockenhuber F, Yeganehfar W, Eisenhuber E, Derfler K, et al: Beneficial effect of renal transplantation on cognitive brain function. Kidney Int 1996;49:833-838.
27.
Teschan PE, Ginn HE, Bourne JR, Ward JW: Neurobehavioral responses to ‘middle molecule' dialysis and transplantation. Trans Am Soc Artif Intern Organs 1976;22:190-194.
28.
Griva K, Thompson D, Jayasena D, Davenport A, Harrison M, Newman SP: Cognitive functioning pre- to post-kidney transplantation - a prospective study. Nephrol Dial Transplant 2006;21:3275-3282.
29.
Harciarek M, Biedunkiewicz B, Lichodziejewska-Niemierko M, Debska-Slizień A, Rutkowski B: Cognitive performance before and after kidney transplantation: a prospective controlled study of adequately dialyzed patients with end-stage renal disease. J Int Neuropsychol Soc 2009;15:684-694.
30.
Schmithorst VJ, Wilke M, Dardzinski BJ, Holland SK: Cognitive functions correlate with white matter architecture in a normal pediatric population: a diffusion tensor MRI study. Hum Brain Mapp 2005;26:139-147.
31.
Fletcher P, McKenna PJ, Friston KJ, Frith CD, Dolan RJ: Abnormal cingulate modulation of fronto-temporal connectivity in schizophrenia. Neuroimage 1999;9:337-342.
32.
Spence SA, Liddle PF, Stefan MD, Hellewell JS, Sharma T, Friston KJ, et al: Functional anatomy of verbal fluency in people with schizophrenia and those at genetic risk. Focal dysfunction and distributed disconnectivity reappraised. Br J Psychiatry 2000;176:52-60.
33.
Oishi K, Faria AV, Hsu J, Tippett D, Mori S, Hillis AE: Critical role of the right uncinate fasciculus in emotional empathy. Ann Neurol 2015;77:68-74.
34.
Dervan L, Poliakov A, Friedman SD, Shaw D, Pihoker C, Roberts JS, et al: Change in fractional anisotropy during treatment of diabetic ketoacidosis in children. Pediatr Res 2014;75:62-66.
35.
Liao Y, Huang X, Wu Q, Yang C, Kuang W, Du M, et al: Is depression a disconnection syndrome? Meta-analysis of diffusion tensor imaging studies in patients with MDD. J Psychiatry Neurosci 2013;38:49-56.
36.
Gons RA, Tuladhar AM, de Laat KF, van Norden AG, van Dijk EJ, Norris DG, et al: Physical activity is related to the structural integrity of cerebral white matter. Neurology 2013;81:971-976.
37.
Okamoto Y, Kemp GJ, Isobe T, Sato E, Hirano Y, Shoda J, et al: Changes in diffusion tensor imaging (DTI) eigenvalues of skeletal muscle due to hybrid exercise training. Magn Reson Imaging 2014;32:1297-1300.
38.
Dineley KT, Hogan D, Zhang WR, Taglialatela G: Acute inhibition of calcineurin restores associative learning and memory in Tg2576 APP transgenic mice. Neurobiol Learn Mem 2007;88:217-224.
© 2016 S. Karger AG, Basel
2016
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.