Chronic kidney disease (CKD) leads to profound metabolic and hemodynamic changes, which damage other organs, such as heart and brain. The brain abnormalities and cognitive deficit progress with the severity of the CKD and are mostly expressed among hemodialysis patients. They have great socio-economic impact. In this review, we present the current knowledge of involved mechanisms.

Department of Radiology University Hospital Kralovske Vinohrady and 3rd Faculty of Medicine Charles University Prague Czech Republic

See more in PubMed

ADESSO S, MAGNUS T, CUZZOCREA S, CAMPOLO M, RISSIEK B, PACIELLO O, AUTORE G, PINTO A, MARZOCCO S. Indoxyl sulfate affects glial function increasing oxidative stress and neuroinflammation in chronic kidney disease: interaction between astrocytes and microglia. Front Pharmacol. 2017;8:370. doi: 10.3389/fphar.2017.00370. PubMed DOI PMC

AKOUDAD S, PORTEGIES ML, KOUDSTAAL PJ, HOFMAN A, Van der LUGT A, IKRAM MA, VERNOOIJ MW. Cerebral microbleeds are associated with an increased risk of stroke: The Rotterdam study. Circulation. 2015;132:509–516. doi: 10.1161/CIRCULATIONAHA.115.016261. PubMed DOI

ARNOLD R, ISSAR T, KRISHNAN AV, PUSSELL BA. Neurological complications in chronic kidney disease. JRSM Cardiovasc Dis. 2016;5 doi: 10.1177/2048004016677687. 2048004016677687. PubMed DOI PMC

ASSOCIATION AP. Diagnostic and statistical manual of mental disorders (DSM-5®) 2013. PubMed

BROUNS R, De DEYN PP. Neurological complications in renal failure: a review. Clin Neurol Neurosurg. 2004;107:1–16. doi: 10.1016/j.clineuro.2004.07.012. PubMed DOI

BRUCK K, STEL VS, GAMBARO G, HALLAN S, VOLZKE H, ARNLOV J, KASTARINEN M, GUESSOUS I, VINHAS J, STENGEL B, BRENNER H, CHUDEK J, ROMUNDSTAD S, TOMSON C, GONZALEZ AO, BELLO AK, FERRIERES J, PALMIERI L, BROWNE G, CAPUANO V, Van BIESEN W, ZOCCALI C, GANSEVOORT R, NAVIS G, ROTHENBACHER D, FERRARO PM, NITSCH D, WANNER C, JAGER KJ, EUROPEAN CKDBC. CKD prevalence varies across the European general population. J Am Soc Nephrol. 2016;27:2135–2147. doi: 10.1681/ASN.2015050542. PubMed DOI PMC

BUGNICOURT JM, GODEFROY O, CHILLON JM, CHOUKROUN G, MASSY ZA. Cognitive disorders and dementia in CKD: the neglected kidney-brain axis. J Am Soc Nephrol. 2013;24:353–363. doi: 10.1681/ASN.2012050536. PubMed DOI

CATCHLOVE SJ, MacPHERSON H, HUGHES ME, CHEN Y, PARRISH TB, PIPINGAS A. An investigation of cerebral oxygen utilization, blood flow and cognition in healthy aging. PLoS One. 2018;13:e0197055. doi: 10.1371/journal.pone.0197055. PubMed DOI PMC

CHEN HJ, WANG YF, WEN J, XU Q, LU GM, ZHANG LJ. Functional-structural relationship in large-scale brain networks of patients with end stage renal disease after kidney transplantation: A longitudinal study. Hum Brain Mapp. 2020;41:328–341. doi: 10.1002/hbm.24804. PubMed DOI PMC

CHEN JJ, ROSAS HD, SALAT DH. Age-associated reductions in cerebral blood flow are independent from regional atrophy. Neuroimage. 2011;55:468–478. doi: 10.1016/j.neuroimage.2010.12.032. PubMed DOI PMC

CHENG BC, CHEN PC, CHEN PC, LU CH, HUANG YC, CHOU KH, LI SH, LIN AN, LIN WC. Decreased cerebral blood flow and improved cognitive function in patients with end-stage renal disease after peritoneal dialysis: An arterial spin-labelling study. Eur Radiol. 2019;29:1415–1424. doi: 10.1007/s00330-018-5675-9. PubMed DOI PMC

CHOU MC, HSIEH TJ, LIN YL, HSIEH YT, LI WZ, CHANG JM, KO CH, KAO EF, JAW TS, LIU GC. 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. doi: 10.3174/ajnr.A3511. PubMed DOI PMC

DANEMAN R, PRAT A. The blood-brain barrier. Cold Spring Harb Perspect Biol. 2015;7:a020412. doi: 10.1101/cshperspect.a020412. PubMed DOI PMC

De DEYN PP, D’HOOGE R, Van BOGAERT PP, MARESCAU B. Endogenous guanidino compounds as uremic neurotoxins. Kidney Int Suppl. 2001;78:S77–83. doi: 10.1046/j.1523-1755.59.s78.51.x. PubMed DOI

DEGUCHI T, ISOZAKI K, YOUSUKE K, TERASAKI T, OTAGIRI M. Involvement of organic anion transporters in the efflux of uremic toxins across the blood-brain barrier. J Neurochem. 2006;96:1051–1059. doi: 10.1111/j.1471-4159.2005.03550.x. PubMed DOI

DOBRIAN AD. ADMA and NOS regulation in chronic renal disease: beyond the old rivalry for l-arginine. Kidney Int. 2012;81:722–724. doi: 10.1038/ki.2011.496. PubMed DOI

DREW DA, KOO BB, BHADELIA R, WEINER DE, DUNCAN S, LA GARZA MM, GUPTA A, TIGHIOUART H, SCOTT T, SARNAK MJ. White matter damage in maintenance hemodialysis patients: a diffusion tensor imaging study. BMC Nephrol. 2017;18:213. doi: 10.1186/s12882-017-0628-0. PubMed DOI PMC

ELIAS MF, DORE GA, DAVEY A. Kidney disease and cognitive function. Contrib Nephrol. 2013;179:42–57. doi: 10.1159/000346722. PubMed DOI PMC

ENGELHARDT B, LIEBNER S. Novel insights into the development and maintenance of the blood-brain barrier. Cell Tissue Res. 2014;355:687–699. doi: 10.1007/s00441-014-1811-2. PubMed DOI PMC

ETGEN T, CHONCHOL M, FORSTL H, SANDER D. Chronic kidney disease and cognitive impairment: a systematic review and meta-analysis. Am J Nephrol. 2012;35:474–482. doi: 10.1159/000338135. PubMed DOI

FINDLAY MD, DAWSON J, DICKIE DA, FORBES KP, McGLYNN D, QUINN T, MARK PB. Investigating the relationship between cerebral blood flow and cognitive function in hemodialysis patients. J Am Soc Nephrol. 2019;30:147–158. doi: 10.1681/ASN.2018050462. PubMed DOI PMC

FRATIGLIONI L, QIU C. Prevention of cognitive decline in ageing: dementia as the target, delayed onset as the goal. Lancet Neurol. 2011;10:778–779. doi: 10.1016/S1474-4422(11)70145-4. PubMed DOI

FREEDMAN BI, SINK KM, HUGENSCHMIDT CE, HUGHES TM, WILLIAMSON JD, WHITLOW CT, PALMER ND, MILLER ME, LOVATO LC, XU J, SMITH SC, LAUNER LJ, BARZILAY JI, COHEN RM, SULLIVAN MD, BRYAN RN, WAGNER BC, BOWDEN DW, MALDJIAN JA, DIVERS J, AA-DHS M, INVESTIGATORS AM. Associations of early kidney disease with brain magnetic resonance imaging and cognitive function in african americans with type 2 diabetes mellitus. Am J Kidney Dis. 2017;70:627–637. doi: 10.1053/j.ajkd.2017.05.006. PubMed DOI PMC

GESUALDO GD, DUARTE JG, ZAZZETTA MS, KUSUMOTA L, SAY KG, PAVARINI SCI, ORLANDI FS. Cognitive impairment of patients with chronic renal disease on hemodialysis and its relationship with sociodemographic and clinical characteristics. Dement Neuropsychol. 2017;11:221–226. doi: 10.1590/1980-57642016dn11-030003. PubMed DOI PMC

GRIVA K, STYGALL J, HANKINS M, DAVENPORT A, HARRISON M, NEWMAN SP. Cognitive impairment and 7-year mortality in dialysis patients. Am J Kidney Dis. 2010;56:693–703. doi: 10.1053/j.ajkd.2010.07.003. PubMed DOI

GUILLEMIN GJ. Quinolinic acid, the inescapable neurotoxin. FEBS J. 2012;279:1356–1365. doi: 10.1111/j.1742-4658.2012.08485.x. PubMed DOI

GUPTA A, LEPPING RJ, YU AS, PEREA RD, HONEA RA, JOHNSON DK, BROOKS WM, BURNS JM. Cognitive function and white matter changes associated with renal transplantation. Am J Nephrol. 2016;43:50–57. doi: 10.1159/000444334. PubMed DOI PMC

HALLMANN R, HORN N, SELG M, WENDLER O, PAUSCH F, SOROKIN LM. Expression and function of laminins in the embryonic and mature vasculature. Physiol Rev. 2005;85:979–1000. doi: 10.1152/physrev.00014.2004. PubMed DOI

HILL NR, FATOBA ST, OKE JL, HIRST JA, O’CALLAGHAN CA, LASSERSON DS, HOBBS FD. Global prevalence of chronic kidney disease - a systematic review and meta-analysis. PLoS One. 2016;11:e0158765. doi: 10.1371/journal.pone.0158765. PubMed DOI PMC

HIRAKATA H, YAO H, OSATO S, IBAYASHI S, ONOYAMA K, OTSUKA M, ICHIYA Y, KUWABARA Y, MASUDA Y, FUJISHIMA M. CBF and oxygen metabolism in hemodialysis patients: effects of anemia correction with recombinant human EPO. Am J Physiol. 1992;262:F737–743. doi: 10.1152/ajprenal.1992.262.5.F737. PubMed DOI

HOSHINO T, OOKAWARA S, GOTO S, MIYAZAWA H, ITO K, UEDA Y, KAKU Y, HIRAI K, NABATA A, MORI H, YOSHIDA I, TABEI K. Evaluation of cerebral oxygenation in patients undergoing long-term hemodialysis. Nephron Clin Pract. 2014;126:57–61. doi: 10.1159/000358432. PubMed DOI

HOSOYA K, TACHIKAWA M. Roles of organic anion/cation transporters at the blood-brain and blood-cerebrospinal fluid barriers involving uremic toxins. Clin Exp Nephrol. 2011;15:478–485. doi: 10.1007/s10157-011-0460-y. PubMed DOI

HUANG J, LI J, FENG C, HUANG X, WONG L, LIU X, NIE Z, XI G. Blood-brain barrier damage as the starting point of leukoaraiosis caused by cerebral chronic hypoperfusion and its involved mechanisms: effect of agrin and aquaporin-4. Biomed Res Int. 2018;2018:2321797. doi: 10.1155/2018/2321797. PubMed DOI PMC

HUGO J, GANGULI M. Dementia and cognitive impairment: epidemiology, diagnosis, and treatment. Clin Geriatr Med. 2014;30:421–442. doi: 10.1016/j.cger.2014.04.001. PubMed DOI PMC

IADECOLA C. The neurovascular unit coming of age: a journey through neurovascular coupling in health and disease. Neuron. 2017;96:17–42. doi: 10.1016/j.neuron.2017.07.030. PubMed DOI PMC

ITO K, OOKAWARA S, UEDA Y, GOTO S, MIYAZAWA H, YAMADA H, KITANO T, SHINDO M, KAKU Y, HIRAI K, YOSHIDA M, HOSHINO T, NABATA A, MORI H, YOSHIDA I, KAKEI M, TABEI K. Factors affecting cerebral oxygenation in hemodialysis patients: cerebral oxygenation associates with pH, hemodialysis duration, serum albumin concentration, and diabetes mellitus. PLoS One. 2015;10:e0117474. doi: 10.1371/journal.pone.0117474. PubMed DOI PMC

IYASERE O, OKAI D, BROWN E. Cognitive function and advanced kidney disease: longitudinal trends and impact on decision-making. Clin Kidney J. 2017;10:89–94. doi: 10.1093/ckj/sfw128. PubMed DOI PMC

JABBARI B, VAZIRI ND. The nature, consequences, and management of neurological disorders in chronic kidney disease. Hemodial Int. 2018;22:150–160. doi: 10.1111/hdi.12587. PubMed DOI

JHA V, GARCIA-GARCIA G, ISEKI K, LI Z, NAICKER S, PLATTNER B, SARAN R, WANG AY, YANG CW. Chronic kidney disease: global dimension and perspectives. Lancet. 2013;382:260–272. doi: 10.1016/S0140-6736(13)60687-X. PubMed DOI

JIANG XL, WEN JQ, ZHANG LJ, ZHENG G, LI X, ZHANG Z, LIU Y, ZHENG LJ, WU L, CHEN HJ, KONG X, LUO S, LU GM, JI XM, ZHANG ZJ. Cerebral blood flow changes in hemodialysis and peritoneal dialysis patients: an arterial-spin labeling MR imaging. Metab Brain Dis. 2016;31:929–936. doi: 10.1007/s11011-016-9829-7. PubMed DOI

JIN MWL, WANG H, HAN X, DIAO Z, GUO W, YANG Z, DING H, WANG Z, ZHANG P, ZHAO P, LV H, LIU W, WANG Z. Disturbed neurovascular coupling in hemodialysis patients. PeerJ. 2020;8:e8989. doi: 10.7717/peerj.8989. PubMed DOI PMC

JING W, JABBARI B, VAZIRI ND. Uremia induces upregulation of cerebral tissue oxidative/inflammatory cascade, down-regulation of Nrf2 pathway and disruption of blood brain barrier. Am J Transl Res. 2018;10:2137–2147. PubMed PMC

JOSHEE P, WOOD AG, WOOD ER, GRUNFELD EA. Meta-analysis of cognitive functioning in patients following kidney transplantation. Nephrol Dial Transplant. 2018;33:1268–1277. doi: 10.1093/ndt/gfx240. PubMed DOI PMC

KEANEY J, CAMPBELL M. The dynamic blood-brain barrier. FEBS J. 2015;282:4067–4079. doi: 10.1111/febs.13412. PubMed DOI

KHATRI M, WRIGHT CB, NICKOLAS TL, YOSHITA M, PAIK MC, KRANWINKEL G, SACCO RL, DECARLI C. Chronic kidney disease is associated with white matter hyperintensity volume: the Northern Manhattan Study (NOMAS) Stroke. 2007;38:3121–3126. doi: 10.1161/STROKEAHA.107.493593. PubMed DOI PMC

KNOPMAN DS, MOSLEY TH, JR, BAILEY KR, JACK CR, Jr, SCHWARTZ GL, TURNER ST. Associations of microalbuminuria with brain atrophy and white matter hyperintensities in hypertensive sibships. J Neurol Sci. 2008;271:53–60. doi: 10.1016/j.jns.2008.03.009. PubMed DOI PMC

KOBAYASHI M, HIRAWA N, YATSU K, KOBAYASHI Y, YAMAMOTO Y, SAKA S, ANDOH D, TOYA Y, YASUDA G, UMEMURA S. Relationship between silent brain infarction and chronic kidney disease. Nephrol Dial Transplant. 2009;24:201–207. doi: 10.1093/ndt/gfn419. PubMed DOI PMC

KOBAYASHI S, IKEDA T, MORIYA H, OHTAKE T, KUMAGAI H. Asymptomatic cerebral lacunae in patients with chronic kidney disease. Am J Kidney Dis. 2004;44:35–41. doi: 10.1053/j.ajkd.2004.03.026. PubMed DOI

KONG X, WEN JQ, QI RF, LUO S, ZHONG JH, CHEN HJ, JI GJ, LU GM, ZHANG LJ. Diffuse interstitial brain edema in patients with end-stage renal disease undergoing hemodialysis: a tract-based spatial statistics study. Medicine (Baltimore) 2014;93:e313. doi: 10.1097/MD.0000000000000313. PubMed DOI PMC

KONTOS HA, RAPER AJ, PATTERSON JL. Analysis of vasoactivity of local pH, PCO2 and bicarbonate on pial vessels. Stroke. 1977;8:358–360. doi: 10.1161/01.STR.8.3.358. PubMed DOI

KRISHNAN AV, KIERNAN MC. Neurological complications of chronic kidney disease. Nat Rev Neurol. 2009;5:542–551. doi: 10.1038/nrneurol.2009.138. PubMed DOI

LAMEIRE N, VANHOLDER R, De SMET R. Uremic toxins and peritoneal dialysis. Kidney Int Suppl. 2001;78:S292–297. doi: 10.1046/j.1523-1755.2001.07820.x. PubMed DOI

LASSEN NA. Normal average value of cerebral blood flow in younger adults is 50 ml/100 g/min. J Cereb Blood Flow Metab. 1985;5:347–349. doi: 10.1038/jcbfm.1985.48. PubMed DOI

LAU WL, NUNES ACF, VASILEVKO V, FLORIOLLI D, LERTPANIT L, SAVOJ J, BANGASH M, YAO Z, SHAH K, NAQVI S, PAGANINI-HILL A, VAZIRI ND, CRIBBS DH, FISHER M. Chronic kidney disease increases cerebral microbleeds in mouse and man. Transl Stroke Res. 2020;11:122–134. doi: 10.1007/s12975-019-00698-8. PubMed DOI PMC

LEE CT, KUO CC, CHEN YM, HSU CY, LEE WC, TSAI YC, NG HY, KUO LC, CHIOU TT, YANG YK, CHENG BC, CHEN JB. Factors associated with blood concentrations of indoxyl sulfate and p-cresol in patients undergoing peritoneal dialysis. Perit Dial Int. 2010a;30:456–463. doi: 10.3747/pdi.2009.00092. PubMed DOI

LEE MC, TING KK, ADAMS S, BREW BJ, CHUNG R, GUILLEMIN GJ. Characterisation of the expression of NMDA receptors in human astrocytes. PLoS One. 2010b;5:e14123. doi: 10.1371/journal.pone.0014123. PubMed DOI PMC

LEENDERS KL, PERANI D, LAMMERTSMA AA, HEATHER JD, BUCKINGHAM P, HEALY MJ, GIBBS JM, WISE RJ, HATAZAWA J, HEROLD S, et al. Cerebral blood flow, blood volume and oxygen utilization. Normal values and effect of age. Brain. 1990;113(Pt 1):27–47. doi: 10.1093/brain/113.1.27. PubMed DOI

LIN YT, WU PH, LEE HH, MUBANGA M, CHEN CS, KUO MC, CHIU YW, KUO PL, HWANG SJ. Indole-3 acetic acid increased risk of impaired cognitive function in patients receiving hemodialysis. Neurotoxicology. 2019;73:85–91. doi: 10.1016/j.neuro.2019.02.019. PubMed DOI

LISOWSKA-MYJAK B. Uremic toxins and their effects on multiple organ systems. Nephron Clin Pract. 2014;128:303–311. doi: 10.1159/000369817. PubMed DOI

LIU CY, YANG Y, JU WN, WANG X, ZHANG HL. Emerging roles of astrocytes in neuro-vascular unit and the tripartite synapse with emphasis on reactive gliosis in the context of Alzheimer’s disease. Front Cell Neurosci. 2018a;12:193. doi: 10.3389/fncel.2018.00193. PubMed DOI PMC

LIU HS, HARTUNG EA, JAWAD AF, WARE JB, LANEY N, PORT AM, GUR RC, HOOPER SR, RADCLIFFE J, FURTH SL, DETRE JA. Regional cerebral blood flow in children and young adults with chronic kidney disease. Radiology. 2018b;288:849–858. doi: 10.1148/radiol.2018171339. PubMed DOI PMC

LIU S, AGALLIU D, YU C, FISHER M. The role of pericytes in blood-brain barrier function and stroke. Curr Pharm Des. 2012;18:3653–3662. doi: 10.2174/138161212802002706. PubMed DOI

LIU WC, TOMINO Y, LU KC. Impacts of indoxyl sulfate and p-cresol sulfate on chronic kidney disease and mitigating effects of AST-120. Toxins (Basel) 2018c;10 doi: 10.3390/toxins10090367. PubMed DOI PMC

MacEWEN C, SUTHERLAND S, DALY J, PUGH C, TARASSENKO L. Relationship between hypotension and cerebral ischemia during hemodialysis. J Am Soc Nephrol. 2017;28:2511–2520. doi: 10.1681/ASN.2016060704. PubMed DOI PMC

MALIK J. Heart disease in chronic kidney disease - review of the mechanisms and the role of dialysis access. J Vasc Access. 2018;19:3–11. doi: 10.5301/jva.5000815. PubMed DOI

MALIK J, KUDLICKA J, LACHMANOVA J, VALERIANOVA A, ROCINOVA K, BARTKOVA M, TESAR V. Tissue ischemia worsens during hemodialysis in end-stage renal disease patients. J Vasc Access no. 2016 doi: 10.5301/jva.50006300. doi: 10.5301/jva.5000630. PubMed DOI

MALKIEWICZ MA, SZARMACH A, SABISZ A, CUBALA WJ, SZUROWSKA E, WINKLEWSKI PJ. Blood-brain barrier permeability and physical exercise. J Neuroinflammation. 2019;16:15. doi: 10.1186/s12974-019-1403-x. PubMed DOI PMC

MALYSZKO J. Mechanism of endothelial dysfunction in chronic kidney disease. Clin Chim Acta. 2010;411:1412–1420. doi: 10.1016/j.cca.2010.06.019. PubMed DOI

MANSOUR A, RASHAD S, NIIZUMA K, FUJIMURA M, TOMINAGA T. A novel model of cerebral hyperperfusion with blood-brain barrier breakdown, white matter injury, and cognitive dysfunction. J Neurosurg no. 2019 doi: 10.3171/2019.7.JNS192121-13. doi: 10.3171/2019.7.JNS19212. PubMed DOI

MARZOCCO S, POPOLO A, BIANCO G, PINTO A, AUTORE G. Pro-apoptotic effect of methylguanidine on hydrogen peroxide-treated rat glioma cell line. Neurochem Int. 2010;57:518–524. doi: 10.1016/j.neuint.2010.06.016. PubMed DOI

MASSON P, WEBSTER AC, HONG M, TURNER R, LINDLEY RI, CRAIG JC. Chronic kidney disease and the risk of stroke: a systematic review and meta-analysis. Nephrol Dial Transplant. 2015;30:1162–1169. doi: 10.1093/ndt/gfv009. PubMed DOI

MATHEW RJ, RABIN P, STONE WJ, WILSON WH. Regional cerebral blood flow in dialysis encephalopathy and primary degenerative dementia. Kidney Int. 1985;28:64–68. doi: 10.1038/ki.1985.119. PubMed DOI

MAZUMDER MK, PAUL R, BHATTACHARYA P, BORAH A. Neurological sequel of chronic kidney disease: From diminished Acetylcholinesterase activity to mitochondrial dysfunctions, oxidative stress and inflammation in mice brain. Sci Rep. 2019;9:3097. doi: 10.1038/s41598-018-37935-3. PubMed DOI PMC

McQUILLAN R, JASSAL SV. Neuropsychiatric complications of chronic kidney disease. Nat Rev Nephrol. 2010;6:471–479. doi: 10.1038/nrneph.2010.83. PubMed DOI

MEYER TW, HOSTETTER TH. Approaches to uremia. J Am Soc Nephrol. 2014;25:2151–2158. doi: 10.1681/ASN.2013121264. PubMed DOI PMC

MOERMAN A, WOUTERS P. Near-infrared spectroscopy (NIRS) monitoring in contemporary anesthesia and critical care. Acta Anaesthesiol Belg. 2010;61:185–194. PubMed

MURRAY AM. Cognitive impairment in the aging dialysis and chronic kidney disease populations: an occult burden. Adv Chronic Kidney Dis. 2008;15:123–132. doi: 10.1053/j.ackd.2008.01.010. PubMed DOI PMC

MURRAY AM, TUPPER DE, KNOPMAN DS, GILBERTSON DT, PEDERSON SL, LI S, SMITH GE, HOCHHALTER AK, COLLINS AJ, KANE RL. Cognitive impairment in hemodialysis patients is common. Neurology. 2006;67:216–223. doi: 10.1212/01.wnl.0000225182.15532.40. PubMed DOI

NAYAK-RAO S, SHENOY MP. Stroke in patients with chronic kidney disease...: How do we approach and manage it? Indian J Nephrol. 2017;27:167–171. doi: 10.4103/0971-4065.202405. PubMed DOI PMC

NETTO JP, ILIFF J, STANIMIROVIC D, KROHN KA, HAMILTON B, VARALLYAY C, GAHRAMANOV S, DALDRUP-LINK H, D’ESTERRE C, ZLOKOVIC B, SAIR H, LEE Y, TAHERI S, JAIN R, PANIGRAHY A, REICH DS, DREWES LR, CASTILLO M, NEUWELT EA. Neurovascular unit: basic and clinical imaging with emphasis on advantages of ferumoxytol. Neurosurgery. 2018;82:770–780. doi: 10.1093/neuros/nyx357. PubMed DOI PMC

OBERMEIER B, DANEMAN R, RANSOHOFF RM. Development, maintenance and disruption of the blood-brain barrier. Nat Med. 2013;19:1584–1596. doi: 10.1038/nm.3407. PubMed DOI PMC

OHTSUKI S, ASABA H, TAKANAGA H, DEGUCHI T, HOSOYA K, OTAGIRI M, TERASAKI T. Role of blood-brain barrier organic anion transporter 3 (OAT3) in the efflux of indoxyl sulfate, a uremic toxin: its involvement in neurotransmitter metabolite clearance from the brain. J Neurochem. 2002;83:57–66. doi: 10.1046/j.1471-4159.2002.01108.x. PubMed DOI

OLIVA-DAMASO E, OLIVA-DAMASO N, RODRIGUEZ-ESPARRAGON F, PAYAN J, BAAMONDE-LABORDA E, GONZALEZ-CABRERA F, SANTANA-ESTUPINAN R, RODRIGUEZ-PEREZ JC. Asymmetric (ADMA) and Symmetric (SDMA) Dimethylarginines in chronic kidney disease: a clinical approach. Int J Mol Sci . 2019;20 doi: 10.3390/ijms20153668. PubMed DOI PMC

OVBIAGELE B, WING JJ, MENON RS, BURGESS RE, GIBBONS MC, SOBOTKA I, GERMAN L, SHARA NM, FERNANDEZ S, JAYAM-TROUTH A, EDWARDS DF, KIDWELL CS. Association of chronic kidney disease with cerebral microbleeds in patients with primary intracerebral hemorrhage. Stroke. 2013;44:2409–2413. doi: 10.1161/STROKEAHA.113.001958. PubMed DOI

PALMER AM. The role of the blood-CNS barrier in CNS disorders and their treatment. Neurobiol Dis. 2010;37:3–12. doi: 10.1016/j.nbd.2009.07.029. PubMed DOI

PAPADOPOULOS G, DOUNOUSI E, PAPATHANASIOU A, PAPATHANAKOS G, TZIMAS P. Cerebral oximetry values in dialyzed surgical patients: a comparison between hemodialysis and peritoneal dialysis. Ren Fail. 2013;35:855–859. doi: 10.3109/0886022X.2013.794675. PubMed DOI

PENG Q, SUN W, LIU W, LIU R, HUANG Y, GROUP CS. Longitudinal relationship between chronic kidney disease and distribution of cerebral microbleeds in patients with ischemic stroke. J Neurol Sci. 2016;362:1–6. doi: 10.1016/j.jns.2016.01.015. PubMed DOI

PHAM NM, RECHT NS, HOSTETTER TH, MEYER TW. Removal of the protein-bound solutes indican and p-cresol sulfate by peritoneal dialysis. Clin J Am Soc Nephrol. 2008;3:85–90. doi: 10.2215/CJN.02570607. PubMed DOI PMC

PI HC, XU YF, XU R, YANG ZK, QU Z, CHEN YQ, LIU GL, DONG J. Cognitive impairment and structural neuroimaging abnormalities among patients with chronic kidney disease. Kidney Blood Press Res. 2016;41:986–996. doi: 10.1159/000452603. PubMed DOI

POLINDER-BOS HA, GARCIA DV, KUIPERS J, ELTING JWJ, ARIES MJH, KRIJNEN WP, GROEN H, WILLEMSEN ATM, Van LAAR PJ, STRIJKERT F, LUURTSEMA G, SLART R, WESTERHUIS R, GANSEVOORT RT, GAILLARD C, FRANSSEN CFM. hemodialysis induces an acute decline in cerebral blood flow in elderly patients. J Am Soc Nephrol. 2018;29:1317–1325. doi: 10.1681/ASN.2017101088. PubMed DOI PMC

PROHOVNIK I, POST J, URIBARRI J, LEE H, SANDU O, LANGHOFF E. Cerebrovascular effects of hemodialysis in chronic kidney disease. J Cereb Blood Flow Metab. 2007;27:1861–1869. doi: 10.1038/sj.jcbfm.9600478. PubMed DOI

QIU Y, LV X, SU H, JIANG G, LI C, TIAN J. Structural and functional brain alterations in end stage renal disease patients on routine hemodialysis: a voxel-based morphometry and resting state functional connectivity study. PLoS One. 2014;9:e98346. doi: 10.1371/journal.pone.0098346. PubMed DOI PMC

REINECKE H, BRAND E, MESTERS R, SCHABITZ WR, FISHER M, PAVENSTADT H, BREITHARDT G. Dilemmas in the management of atrial fibrillation in chronic kidney disease. J Am Soc Nephrol. 2009;20:705–711. doi: 10.1681/ASN.2007111207. PubMed DOI

SEDAGHAT S, VERNOOIJ MW, LOEHRER E, MATTACE-RASO FU, HOFMAN A, Van der LUGT A, FRANCO OH, DEHGHAN A, IKRAM MA. Kidney function and cerebral blood flow: the Rotterdam Study. J Am Soc Nephrol. 2016;27:715–721. doi: 10.1681/ASN.2014111118. PubMed DOI PMC

SETIADI A, KORIM WS, ELSAAFIEN K, YAO ST. The role of the blood-brain barrier in hypertension. Exp Physiol. 2018;103:337–342. doi: 10.1113/EP086434. PubMed DOI

SHARIF Y, JUMAH F, COPLAN L, KROSSER A, SHARIF K, TUBBS RS. Blood brain barrier: A review of its anatomy and physiology in health and disease. Clin Anat. 2018;31:812–823. doi: 10.1002/ca.23083. PubMed DOI

SHIMA H, ISHIMURA E, NAGANUMA T, ICHII M, YAMASAKI T, MORI K, NAKATANI T, INABA M. Decreased kidney function is a significant factor associated with silent cerebral infarction and periventricular hyperintensities. Kidney Blood Press Res. 2011;34:430–438. doi: 10.1159/000328722. PubMed DOI

SHIMA H, MORI T, OOI M, SONODA M, SHOJI T, ISHIMURA E, OKAMURA M, ISHIZAKA N, INABA M. Silent cerebral microbleeds and longitudinal risk of renal and cardiovascular events in patients with CKD. Clin J Am Soc Nephrol. 2016;11:1557–1565. doi: 10.2215/CJN.13481215. PubMed DOI PMC

SINK KM, DIVERS J, WHITLOW CT, PALMER ND, SMITH SC, XU J, HUGENSCHMIDT CE, WAGNER BC, WILLIAMSON JD, BOWDEN DW, MALDJIAN JA, FREEDMAN BI. Cerebral structural changes in diabetic kidney disease: African American-Diabetes Heart Study MIND. Diabetes Care. 2015;38:206–212. doi: 10.2337/dc14-1231. PubMed DOI PMC

STAMATOVIC SM, KEEP RF, ANDJELKOVIC AV. Brain endothelial cell-cell junctions: how to "open" the blood brain barrier. Curr Neuropharmacol. 2008;6:179–192. doi: 10.2174/157015908785777210. PubMed DOI PMC

STUBBS JR, HOUSE JA, OCQUE AJ, ZHANG S, JOHNSON C, KIMBER C, SCHMIDT K, GUPTA A, WETMORE JB, NOLIN TD, SPERTUS JA, YU AS. Serum trimethylamine-n-oxide is elevated in CKD and correlates with coronary atherosclerosis burden. J Am Soc Nephrol. 2016;27:305–313. doi: 10.1681/ASN.2014111063. PubMed DOI PMC

TAMURA MK, PAJEWSKI NM, BRYAN RN, WEINER DE, DIAMOND M, Van BUREN P, TAYLOR A, BEDDHU S, ROSENDORFF C, JAHANIAN H, ZAHARCHUK G, GROUP SSR. Chronic kidney disease, cerebral blood flow, and white matter volume in hypertensive adults. Neurology. 2016;86:1208–1216. doi: 10.1212/WNL.0000000000002527. PubMed DOI PMC

TAMURA MK, YAFFE K. Dementia and cognitive impairment in ESRD: diagnostic and therapeutic strategies. Kidney Int. 2011;79:14–22. doi: 10.1038/ki.2010.336. PubMed DOI PMC

TARUMI T, ZHANG R. Cerebral blood flow in normal aging adults: cardiovascular determinants, clinical implications, and aerobic fitness. J Neurochem. 2018;144:595–608. doi: 10.1111/jnc.14234. PubMed DOI PMC

TASKER RC. Brain vascular and hydrodynamic physiology. Semin Pediatr Surg. 2013;22:168–173. doi: 10.1053/j.sempedsurg.2013.10.003. PubMed DOI PMC

TING KK, BREW BJ, GUILLEMIN GJ. Effect of quinolinic acid on human astrocytes morphology and functions: implications in Alzheimer’s disease. J Neuroinflammation. 2009;6:36. doi: 10.1186/1742-2094-6-36. PubMed DOI PMC

TRIPATHI M, VIBHA D. Reversible dementias. Indian J Psychiatry. 2009;51(Suppl 1):S52–S55. PubMed PMC

TSURUYA K, YOSHIDA H. Brain atrophy and cognitive impairment in chronic kidney disease. Contrib Nephrol. 2018;196:27–36. doi: 10.1159/000485694. PubMed DOI

UENO M, TOMIMOTO H, AKIGUCHI I, WAKITA H, SAKAMOTO H. Blood-brain barrier disruption in white matter lesions in a rat model of chronic cerebral hypoperfusion. J Cereb Blood Flow Metab. 2002;22:97–104. doi: 10.1097/00004647-200201000-00012. PubMed DOI

VALERIANOVA A, LACHMANOVA J, KOVAROVA L, KMENTOVA T, BARTKOVA M, MALIK J. Factors responsible for cerebral hypoxia in hemodialysis population. Physiol Res. 2019;68:651–658. doi: 10.33549/physiolres.934064. PubMed DOI

van SANDWIJK MS, TEN BERGE IJ, MAJOIE CB, CAAN MW, De SONNEVILLE LM, Van GOOL WA, BEMELMAN FJ. Cognitive changes in chronic kidney disease and after transplantation. Transplantation. 2016;100:734–742. doi: 10.1097/TP.0000000000000968. PubMed DOI

VANHOLDER R, MEERT N, Van BIESEN W, MEYER T, HOSTETTER T, DHONDT A, ELOOT S. Why do patients on peritoneal dialysis have low blood levels of protein-bound solutes? Nat Clin Pract Nephrol. 2009;5:130–131. doi: 10.1038/ncpneph1023. PubMed DOI

VANHOLDER RC, GLORIEUX G, De SMET R, De DEYN PP. Low water-soluble uremic toxins. Adv Ren Replace Ther. 2003;10:257–269. doi: 10.1053/j.arrt.2003.08.003. PubMed DOI

VARATHARAJ A, GALEA I. The blood-brain barrier in systemic inflammation. Brain Behav Immun. 2017;60:1–12. doi: 10.1016/j.bbi.2016.03.010. PubMed DOI

VAVILALA MS, LEE LA, LAM AM. Cerebral blood flow and vascular physiology. Anesthesiol Clin North Am. 2002;20:247–264, v. doi: 10.1016/S0889-8537(01)00012-8. PubMed DOI

VEMURI P, KNOPMAN DS, JACK CR, JR, LUNDT ES, WEIGAND SD, ZUK SM, THOSTENSON KB, REID RI, KANTARCI K, SLININ Y, LAKSHMINARAYAN K, DAVEY CS, MURRAY A. Association of kidney function biomarkers with brain MRI findings: The BRINK Study. J Alzheimers Dis. 2017;55:1069–1082. doi: 10.3233/JAD-160834. PubMed DOI PMC

VIGGIANO D, WAGNER CA, BLANKESTIJN PJ, BRUCHFELD A, FLISER D, FOUQUE D, FRISCHE S, GESUALDO L, GUTIERREZ E, GOUMENOS D, HOORN EJ, ECKARDT KU, KNAUSS S, KONIG M, MALYSZKO J, MASSY Z, NITSCH D, PESCE F, RYCHLIK I, SOLER MJ, SPASOVSKI G, STEVENS KI, TREPICCIONE F, WANNER C, WIECEK A, ZOCCALI C, UNWIN R, CAPASSO G. Mild cognitive impairment and kidney disease: clinical aspects. Nephrol Dial Transplant. 2020;35:10–17. doi: 10.1093/ndt/gfz051. PubMed DOI

VOGELS SC, EMMELOT-VONK MH, VERHAAR HJ, KOEK HL. The association of chronic kidney disease with brain lesions on MRI or CT: a systematic review. Maturitas. 2012;71:331–336. doi: 10.1016/j.maturitas.2012.01.008. PubMed DOI

VORSTRUP S, LASS P, WALDEMAR G, BRANDI L, SCHMIDT JF, JOHNSEN A, PAULSON OB. Increased cerebral blood flow in anemic patients on long-term hemodialytic treatment. J Cereb Blood Flow Metab. 1992;12:745–749. doi: 10.1038/jcbfm.1992.105. PubMed DOI

WADA M, NAGASAWA H, ISEKI C, TAKAHASHI Y, SATO H, ARAWAKA S, KAWANAMI T, KURITA K, DAIMON M, KATO T. Cerebral small vessel disease and chronic kidney disease (CKD): results of a cross-sectional study in community-based Japanese elderly. J Neurol Sci. 2008;272:36–42. doi: 10.1016/j.jns.2008.04.029. PubMed DOI

WAGNER M, JURCOANE A, VOLZ S, MAGERKURTH J, ZANELLA FE, NEUMANN-HAEFELIN T, DEICHMANN R, SINGER OC, HATTINGEN E. Age-related changes of cerebral autoregulation: new insights with quantitative T2′-mapping and pulsed arterial spin-labeling MR imaging. AJNR Am J Neuroradiol. 2012;33:2081–2087. doi: 10.3174/ajnr.A3138. PubMed DOI PMC

WEBSTER AC, NAGLER EV, MORTON RL, MASSON P. Chronic kidney disease. Lancet. 2017;389:1238–1252. doi: 10.1016/S0140-6736(16)32064-5. PubMed DOI

WILLIAMS LR, LEGGETT RW. Reference values for resting blood flow to organs of man. Clin Phys Physiol Meas. 1989;10:187–217. doi: 10.1088/0143-0815/10/3/001. PubMed DOI

XIAO L, LAN W, SUN W, DAI Q, XIONG Y, LI L, ZHOU Y, ZHENG P, FAN W, MA N, GUO Z, CHEN X, XIE X, XU L, ZHU W, XU G, LIU X. Chronic kidney disease in patients with lacunar stroke: association with enlarged perivascular spaces and total magnetic resonance imaging burden of cerebral small vessel disease. Stroke. 2015;46:2081–2086. doi: 10.1161/STROKEAHA.114.008155. PubMed DOI

YASUI-FURUKORI N, TARAKITA N, UEMATSU W, SAITO H, NAKAMURA K, OHYAMA C, SUGAWARA N. Delirium in hemodialysis predicts mortality: a single-center, long-term observational study. Neuropsychiatr Dis Treat. 2017;13:3011–3016. doi: 10.2147/NDT.S152355. PubMed DOI PMC

YIN Y, LI M, LI C, MA X, YAN J, WANG T, FU S, HUA K, WU Y, ZHAN W, JIANG G. Reduced white matter integrity with cognitive impairments in end stage renal disease. Front Psychiatry. 2018;9:143. doi: 10.3389/fpsyt.2018.00143. PubMed DOI PMC

ZEPEDA-OROZCO D, QUIGLEY R. Dialysis disequilibrium syndrome. Pediatr Nephrol. 2012;27:2205–2211. doi: 10.1007/s00467-012-2199-4. PubMed DOI PMC

ZHANG R, LIU K, YANG L, ZHOU T, QIAN S, LI B, PENG Z, LI M, SANG S, JIANG Q, SUN G. Reduced white matter integrity and cognitive deficits in maintenance hemodialysis ESRD patients: a diffusion-tensor study. Eur Radiol. 2015;25:661–668. doi: 10.1007/s00330-014-3466-5. PubMed DOI

ZOCCALI C, BENEDETTO FA, MAAS R, MALLAMACI F, TRIPEPI G, MALATINO LS, BOGER R, INVESTIGATORS C. Asymmetric dimethylarginine, C-reactive protein, and carotid intima-media thickness in end-stage renal disease. J Am Soc Nephrol. 2002;13:490–496. PubMed

New Porcine Model of Arteriovenous Fistula Documents Increased Coronary Blood Flow at the Cost of Brain Perfusion

The effect of high-flow arteriovenous fistulas on systemic haemodynamics and brain oxygenation