Review
BibTex RIS Cite

Central Nervous System Response to Chronic Kidney Disease

Year 2022, Volume: 17 Issue: 3, 198 - 209, 02.11.2022

Güray Okyar Dursun Alper Yılmaz Mehmet Salih Yıldırım Metin Yıldız

https://doi.org/10.17517/ksutfd.917658

Abstract

 Abstract
Due to the aging of the human population, the prevalence of chronic diseases such as chronic kidney disease (CKD) is increasing every year. Chronic kidney disease is a general term that refers to heterogeneous disorders that affect kidney structure and function. Decrease in glomerular filtration can be defined as chronic and progressive deterioration in fluid-solute balance, metabolic and endocrine functions of the kidney. CKD often affects the elderly. With the advancement of age, some structural and functional changes occur in the kidneys. Therefore, the number of patients suffering from mild and moderate CKD is expected to increase in the future. CKD leads to the deep metabolic and hemodynamic changes that damage other organs, such as the heart and brain. Central nervous system abnormalities and cognitive deficits progress with the severity of CKD and occurs mostly among hemodialysis patients. It also has great socio-economic effects on individuals. Since symptoms of CKD are not often found in patients, early recognition of risk factors is the main point. For this reason, it is necessary to identify possible protective and preventive treatments to be applied in at-risk groups and to examine these mechanisms for the treatment of the disease. This review provides available information on the relevant mechanisms.

Keywords

Functional brain changes Neurocognitive ability Renal replacement methods

References

  • 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. Nephrology Dialysis Transplantation. 2015;30(7):1162-1169.
  • Brück K, Stel VS, Gambaro G, Hallan S, Völzke H, Ärnlöv J et al. CKD prevalence varies across the European general population. Journal of the American Society of Nephrology. 2016;27(7):2135-2147.
  • Hill NR, Fatoba ST, Oke JL, Hirst JA, O’Callaghan CA, Lasserson DS et al. Global prevalence of chronic kidney disease–A systematic review and meta-analysis. PloS one. 2016;11(7):e0158765.
  • Tanrıverdi MH. Kronik böbrek yetmezliği. Konuralp Tıp Dergisi. 2010;2(2):27-32.
  • Rothwell P, Coull A, Giles M, Howard S, Silver L, Bull L et al. Change in stroke incidence, mortality, case-fatality, severity, and risk factors in Oxfordshire, UK from 1981 to 2004 (Oxford Vascular Study). The Lancet. 2004;363(9425):1925-1933.
  • El Husseini N, Kaskar O, Goldstein LB. Chronic kidney disease and stroke. Advances in chronic kidney disease. 2014;21(6):500-508.
  • Reinecke H, Brand E, Mesters R, Schäbitz W-R, Fisher M, Pavenstädt H et al. Dilemmas in the management of atrial fibrillation in chronic kidney disease. Journal of the American Society of Nephrology. 2009;20(4):705-711.
  • Hamed SA. Neurologic conditions and disorders of uremic syndrome of chronic kidney disease: Presentations, causes, and treatment strategies. Expert Rev Clin Pharmacol. 2019;12(1):61-90.
  • Seifter JL, Samuels MA. Uremic encephalopathy and other brain disorders associated with renal failure. Seminars in neurology. 2011;31(2):139-143.
  • McQuillan R, Jassal SV. Neuropsychiatric complications of chronic kidney disease. Nature Reviews Nephrology. 2010;6(8):471.
  • Brouns R, De Deyn P. Neurological complications in renal failure: A review. Clinical neurology and neurosurgery. 2004;107(1):1-16.
  • Malyszko J. Mechanism of endothelial dysfunction in chronic kidney disease. Clinica chimica acta. 2010;411(19-20):1412-1420.
  • Arnold R, Issar T, Krishnan AV, Pussell BA. Neurological complications in chronic kidney disease. JRSM cardiovascular disease. 2016;5:2048004016677687.
  • Fazekas G, Fazekas F, Schmidt R, Kapeller P, Offenbacher H, Krejs GJ. Brain MRI findings and cognitive impairment in patients undergoing chronic hemodialysis treatment. Journal of the neurological sciences. 1995;134(1-2):83-88.
  • Varela FJ. Patterns of life: Intertwining identity and cognition. Brain and cognition. 1997;34(1):72-87.
  • Mistry K. Dialysis disequilibrium syndrome prevention and management. International journal of nephrology and renovascular disease. 2019;12:69.
  • Nakai S, Wakai K, Kanda E, Kawaguchi K, Sakai K, Kitaguchi N. Is hemodialysis itself a risk factor for dementia? An analysis of nationwide registry data of patients on maintenance hemodialysis in Japan. Renal Replacement Therapy. 2018;4(1):12.
  • van Zwieten A, Wong G, Ruospo M, Palmer SC, Barulli MR, Iurillo A et al. Prevalence and patterns of cognitive impairment in adult hemodialysis patients: the COGNITIVE-HD study. Nephrology Dialysis Transplantation. 2018;33(7):1197-1206.
  • Etgen T, Chonchol M, Förstl H, Sander D. Chronic kidney disease and cognitive impairment: A systematic review and meta-analysis. American journal of nephrology. 2012;35(5):474-482.
  • Association AP. American Psychiatric Association DSM-5 Development. Proposed Revisions/Somatic Symptom Disorders/J. 2010;2.
  • Bevins EA, Peters J, Léger GC. The Diagnosis and Management of Reversible Dementia Syndromes. Current Treatment Options in Neurology. 2021;23(1):1-13.
  • Hugo J, Ganguli M. Dementia and cognitive impairment: epidemiology, diagnosis, and treatment. Clinics in geriatric medicine. 2014;30(3):421-442.
  • Fratiglioni L, Qiu C. Prevention of cognitive decline in ageing: dementia as the target, delayed onset as the goal. The Lancet Neurology. 2011;10(9):778-779.
  • Viggiano D, Wagner CA, Martino G, Nedergaard M, Zoccali C, Unwin R et al. Mechanisms of cognitive dysfunction in CKD. Nature Reviews Nephrology. 2020;16(8):452-469.
  • Zammit AR, Katz MJ, Zimmerman ME, Bitzer M, Lipton RB. Low eGFR is associated with dysexecutive and amnestic mild cognitive impairment. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring. 2015;1(2):152-159.
  • Elias MF, Elias PK, Seliger SL, Narsipur SS, Dore GA, Robbins MA. Chronic kidney disease, creatinine and cognitive functioning. Nephrology Dialysis Transplantation. 2009;24(8):2446-2452.
  • Hung P-H, Yeh C-C, Hsiao C-Y, Sung P-S, Muo C-H, Sung F-C et al. End stage renal disease is associated with development of dementia. Oncotarget. 2017;8(64):107348.
  • Seyahi N, Ates K, Suleymanlar G. Türkiye’de Renal Replasman Tedavilerinin Güncel Durumu: Türk Nefroloji Derneği Kayıt Sistemi 2016 Yılı Özet Raporu Current Status of Renal Replacement Therapies in Turkey: Turkish Society of Nephrology Registry 2016 Summary Report. 2018.
  • Ozcan H, Yucel A, Avşar U, Çankaya 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. Transplantation proceedings; 2015;47(5):1348-1351.
  • Tomlinson JA, Wheeler DC. The role of trimethylamine N-oxide as a mediator of cardiovascular complications in chronic kidney disease. Kidney international. 2017;92(4):809-815.
  • Busch M, Fleck C, Wolf G, Stein G. Asymmetrical (ADMA) and symmetrical dimethylarginine (SDMA) as potential risk factors for cardiovascular and renal outcome in chronic kidney disease–possible candidates for paradoxical epidemiology? Amino Acids. 2006;30(3):225-232.
  • Gryp T, Vanholder R, Vaneechoutte M, Glorieux G. p-Cresyl sulfate. Toxins. 2017;9(2):52.
  • Barreto FC, Barreto DV, Liabeuf S, Meert N, Glorieux G, Temmar M et al. Serum indoxyl sulfate is associated with vascular disease and mortality in chronic kidney disease patients. Clinical Journal of the American Society of Nephrology. 2009;4(10):1551-1558.
  • Zhang D-L, Liu J, Liu S, Zhang Y, Liu W-H. The differences of asymmetric dimethylarginine removal by different dialysis treatments. Renal failure. 2010;32(8):935-940.
  • Watanabe K, Watanabe T, Nakayama M. Cerebro-renal interactions: impact of uremic toxins on cognitive function. Neurotoxicology. 2014;44:184-193.
  • Lameire N, Vanholder R, De Smet R. Uremic toxins and peritoneal dialysis. Kidney Int Suppl. 2001;78:292-297.
  • Krieter DH, Hackl A, Rodriguez A, Chenine L, Moragues HL, Lemke H-D et al. Protein-bound uraemic toxin removal in haemodialysis and post-dilution haemodiafiltration. Nephrology Dialysis Transplantation. 2010;25(1):212-218.
  • Thornalley PJ. Glycation free adduct accumulation in renal disease: the new AGE. Pediatric Nephrology. 2005;20(11):1515-1522.
  • Mathew AT, Fishbane S, Obi Y, Kalantar-Zadeh K. Preservation of residual kidney function in hemodialysis patients: reviving an old concept. Kidney international. 2016;90(2):262-271.
  • Simões-Silva L, Araujo R, Pestana M, Soares-Silva I, Sampaio-Maia B. The microbiome in chronic kidney disease patients undergoing hemodialysis and peritoneal dialysis. Pharmacological research. 2018;130:143-151.
  • McIntyre CW, Salerno FR. Diagnosis and treatment of intradialytic hypotension in maintenance hemodialysis patients. Clinical Journal of the American Society of Nephrology. 2018;13(3):486-489.
  • Finnerty FA, Witkin L, Fazekas JF. Cerebral hemodynamics during cerebral ischemia induced by acute hypotension. The Journal of clinical investigation. 1954;33(9):1227-1232.
  • Fukunishi I, Kitaoka T, Shirai T, Kino K, Kanematsu E, Sato Y. Psychiatric disorders among patients undergoing hemodialysis therapy. Nephron. 2002;91(2):344-347.
  • Tamura MK, Yaffe K. Dementia and cognitive impairment in ESRD: diagnostic and therapeutic strategies. Kidney international. 2011;79(1):14-22.
  • Murray AM. Cognitive impairment in the aging dialysis and chronic kidney disease populations: an occult burden. Advances in chronic kidney disease. 2008;15(2):123-132.
  • Posselt J, Harbeck B, Rahvar AH, Kropp P, Haas CS. Improved cognitive function after kidney transplantation compared to hemodialysis. Ther Apher Dial. 2021;25(6):931-938.
  • Simpson IA, Carruthers A, Vannucci SJ. Supply and demand in cerebral energy metabolism: the role of nutrient transporters. J Cereb Blood Flow Metab. 2007;27(11):1766-1791.
  • Villringer A, Planck J, Hock C, Schleinkofer L, Dirnagl U. Near infrared spectroscopy (NIRS): a new tool to study hemodynamic changes during activation of brain function in human adults. Neuroscience letters. 1993;154(1-2):101-104.
  • Takahashi T, Shirane R, Sato S, Yoshimoto T. Developmental changes of cerebral blood flow and oxygen metabolism in children. American journal of neuroradiology. 1999;20(5):917-922.
  • Lassen N, Munck O. The cerebral blood flow in man determined by the use of radioactive krypton. Acta Physiologica Scandinavica. 1955;33(1):30-49.
  • Chen JJ, Rosas HD, Salat DH. Age-associated reductions in cerebral blood flow are independent from regional atrophy. Neuroimage. 2011;55(2):468-478.
  • Zauner A, Muizelaar JP. Brain metabolism and cerebral blood flow. Head injury. 1997:89-99.
  • Muller M, van der Graaf Y, Visseren FL, Vlek AL, Mali WP, Geerlings MI et al. Blood pressure, cerebral blood flow, and brain volumes. The SMART-MR study. Journal of hypertension. 2010;28(7):1498-1505.
  • Lee C, Lopez OL, Becker JT, Raji C, Dai W, Kuller LH et al. Imaging cerebral blood flow in the cognitively normal aging brain with arterial spin labeling: implications for imaging of neurodegenerative disease. Journal of Neuroimaging. 2009;19(4):344-352.
  • Lu H, Xu F, Rodrigue KM, Kennedy KM, Cheng Y, Flicker B, et al. Alterations in cerebral metabolic rate and blood supply across the adult lifespan. Cerebral cortex. 2011;21(6):1426-1434.
  • Malik J, Kudlicka J, Lachmanova J, Valerianova A, Rocinova K, Bartkova M et al. Tissue ischemia worsens during hemodialysis in end-stage renal disease patients. The journal of vascular access. 2017;18(1):47-51.
  • Prohovnik I, Post J, Uribarri J, Lee H, Sandu O, Langhoff E. Cerebrovascular effects of hemodialysis in chronic kidney disease. Journal of Cerebral Blood Flow & Metabolism. 2007;27(11):1861-1869.
  • Ito K, Ookawara S, Ueda Y, Goto S, Miyazawa H, Yamada H et al. Factors affecting cerebral oxygenation in hemodialysis patients: cerebral oxygenation associates with pH, hemodialysis duration, serum albumin concentration, and diabetes mellitus. PLoS One. 2015;10(2):e0117474.
  • Hoshino T, Ookawara S, Goto S, Miyazawa H, Ito K, Ueda Y, et al. Evaluation of cerebral oxygenation in patients undergoing long-term hemodialysis. Nephron Clinical Practice. 2014;126(1):57-61.
  • Ookawara S, Ito K, Sasabuchi Y, Ueda Y, Hayasaka H, Kofuji M et al. Association between Cerebral Oxygenation, as Evaluated with Near-Infrared Spectroscopy, and Cognitive Function in Patients Undergoing Hemodialysis. Nephron. 2021:1-8.
  • Regolisti G, Maggiore U, Cademartiri C, Cabassi A, Caiazza A, Tedeschi S, et al. Cerebral blood flow decreases during intermittent hemodialysis in patients with acute kidney injury, but not in patients with end-stage renal disease. Nephrology Dialysis Transplantation. 2013;28(1):79-85.
  • Minato S, Ookawara S, Ito K, Hayasaka H, Kofuji M, Uchida T, et al. Continuous monitoring of changes in cerebral oxygenation during hemodialysis in a patient with acute congestive heart failure. Journal of Artificial Organs. 2019:1-4.
  • Yoon S, Zuccarello M, Rapoport RM. pCO2 and pH regulation of cerebral blood flow. Frontiers in physiology. 2012;3:365.
  • Tamura MK, Pajewski NM, Bryan RN, Weiner DE, Diamond M, Van Buren P et al. Chronic kidney disease, cerebral blood flow, and white matter volume in hypertensive adults. Neurology. 2016;86(13):1208-1216.
  • Jiang XL, Wen JQ, Zhang LJ, Zheng G, Li X, Zhang Z et al. Cerebral blood flow changes in hemodialysis and peritoneal dialysis patients: an arterial-spin labeling MR imaging. Metabolic brain disease. 2016;31(4):929-936.
  • Hirakata H, Yao H, Osato S, Ibayashi S, Onoyama K, Otsuka M et al. CBF and oxygen metabolism in hemodialysis patients: effects of anemia correction with recombinant human EPO. American Journal of Physiology-Renal Physiology. 1992;262(5):737-743.
  • Nanba T, Ogasawara K, Nishimoto H, Fujiwara S, Kuroda H, Sasaki M et al. Postoperative cerebral white matter damage associated with cerebral hyperperfusion and cognitive impairment after carotid endarterectomy: a diffusion tensor magnetic resonance imaging study. Cerebrovascular Diseases. 2012;34(5-6):358-367.
  • Rink C, Khanna S. Significance of brain tissue oxygenation and the arachidonic acid cascade in stroke. Antioxidants & redox signaling. 2011;14(10):1889-1903.
  • Yılmaz N. Kan-Beyin bariyerinin fizyopatolojisi. Van Tıp Dergisi. 2006;13(1):25-7.
  • Stamatovic SM, Keep RF, Andjelkovic AV. Brain endothelial cell-cell junctions: How to "open" the blood brain barrier. Curr Neuropharmacol. 2008;6(3):179-92.
  • Köksel T, Güleryüz A. Kan-Beyin Bariyeri. Mersin Üniversitesi Tip Fakültesi Dergisi. 2012;2(1):94-99.
  • Pardridge WM. Brain metabolism: A perspective from the blood-brain barrier. Physiological reviews. 1983;63(4):1481-1535.
  • Yilmaz O, Taskiran D. Astrosit Hücre Kültürlerinde pH Değişikliğinin Yarattığı Toksisite ve Glutatyonun Koruyucu Etkisi. Journal of Neurological Sciences. 2010;27(1):61-68.
  • Bell AH, Miller SL, Castillo-Melendez M, Malhotra A. The neurovascular unit: effects of brain insults during the perinatal period. Frontiers in neuroscience. 2020;13:1452.
  • Haluska M, Anthony ML. Osmotic blood-brain barrier modification for the treatment of malignant brain tumors. Clinical journal of oncology nursing. 2004;8(3):263-267.
  • 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. Scientific reports. 2019;9(1):1-22.
  • 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. American journal of translational research. 2018;10(7):2137.
  • Lau WL, Nunes AC, Vasilevko V, Floriolli D, Lertpanit L, Savoj J et al. Chronic kidney disease increases cerebral microbleeds in mouse and man. Translational stroke research. 2020;11(1):122-134.
  • MacKenzie ET, Strandgaard S, Graham DI, Jones JV, Harper AM, Farrar JK. Effects of acutely induced hypertension in cats on pial arteriolar caliber, local cerebral blood flow, and the blood-brain barrier. Circulation research. 1976;39(1):33-41.
  • Horani MH, Mooradian AD. Effect of diabetes on the blood brain barrier. Current pharmaceutical design. 2003;9(10):833-840.
  • Banks W, Farr S, Salameh T, Niehoff M, Rhea E, Morley J et al. Triglycerides cross the blood–brain barrier and induce central leptin and insulin receptor resistance. International journal of obesity. 2018;42(3):391-397.
  • Jin M, Wang L, Wang H, Han X, Diao Z, Guo W et al. Disturbed neurovascular coupling in hemodialysis patients. PeerJ. 2020;8:e8989.
  • Soto-Rojas LO, Pacheco-Herrero M, Martínez-Gómez PA, Campa-Córdoba B, Apátiga-Pérez R, Villegas-Rojas MM, et al. The Neurovascular Unit Dysfunction in Alzheimer’s Disease. International Journal of Molecular Sciences. 2021;22(4):2022.
  • 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(4):478-485.
  • De Deyn PP, Vanholder R, Eloot S, Glorieux G. Progress in uremic toxin research: Guanidino compounds as uremic (neuro) toxins. Seminars in dialysis; 2009:22(4):340-345.
  • Ohno K, Ito M, Ichihara M, Ito M. Molecular hydrogen as an emerging therapeutic medical gas for neurodegenerative and other diseases. Oxidative medicine and cellular longevity. 2012;2012:353152.
  • Baranyi A, Amouzadeh-Ghadikolai O, Von Lewinski D, Breitenecker RJ, Stojakovic T, März W et al. Beta-trace protein as a new non-invasive immunological marker for quinolinic acid-induced impaired blood-brain barrier integrity. Scientific reports. 2017;7(1):1-8.
  • Lester D. The concentration of neurotransmitter metabolites in the cerebrospinal fluid of suicidal individuals: a meta-analysis. Pharmacopsychiatry. 1995;28(02):45-50.
  • Kidwell CS, Chalela JA, Saver JL, Starkman S, Hill MD, Demchuk AM et al. Comparison of MRI and CT for detection of acute intracerebral hemorrhage. Jama. 2004;292(15):1823-1830.
  • Freedman BI, Sink KM, Hugenschmidt CE, Hughes TM, Williamson JD, Whitlow CT et al. Associations of early kidney disease with brain magnetic resonance imaging and cognitive function in African Americans with type 2 diabetes mellitus. American Journal of Kidney Diseases. 2017;70(5):627-637.
  • Solomon MA, van der Plas E, Langbehn KE, Novak M, Schultz JL, Koscik TR et al. Early pediatric chronic kidney disease is associated with brain volumetric gray matter abnormalities. Pediatric Research. 2020:1-7.
  • Sedaghat S, Cremers LG, De Groot M, Hoorn EJ, Hofman A, Van Der Lugt A et al. Kidney function and microstructural integrity of brain white matter. Neurology. 2015;85(2):154-161.
  • Borgwardt SJ, Riecher-Rössler A, Dazzan P, Chitnis X, Aston J, Drewe M et al. Regional gray matter volume abnormalities in the at risk mental state. Biological psychiatry. 2007;61(10):1148-1156.
  • Hsieh T-J, Chang J-M, Chuang H-Y, Ko C-H, Hsieh M-L, Liu G-C et al. End-stage renal disease: in vivo diffusion-tensor imaging of silent white matter damage. Radiology. 2009;252(2):518-525.
  • Mu J, Chen T, Li P, Ding D, Ma X, Zhang M et al. Altered white matter microstructure mediates the relationship between hemoglobin levels and cognitive control deficits in end‐stage renal disease patients. Human brain mapping. 2018;39(12):4766-4775.
  • Shima H, Ishimura E, Naganuma T, Ichii M, Yamasaki T, Mori K et al. Decreased kidney function is a significant factor associated with silent cerebral infarction and periventricular hyperintensities. Kidney and Blood Pressure Research. 2011;34(6):430-438.
  • Kobayashi M, Hirawa N, Yatsu K, Kobayashi Y, Yamamoto Y, Saka S et al. Relationship between silent brain infarction and chronic kidney disease. Nephrology Dialysis Transplantation. 2009;24(1):201-207.
  • Yao H, Araki Y, Takashima Y, Uchino A, Yuzuriha T, Hashimoto M. Chronic kidney disease and subclinical brain infarction increase the risk of vascular cognitive impairment: The Sefuri study. Journal of Stroke and Cerebrovascular Diseases. 2017;26(2):420-424.
  • 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. Journal of the neurological sciences. 2016;362:1-6.
  • Ovbiagele B, Wing JJ, Menon RS, Burgess RE, Gibbons MC, Sobotka I et al. Association of chronic kidney disease with cerebral microbleeds in patients with primary intracerebral hemorrhage. Stroke. 2013;44(9):2409-2413.
  • Xiao L, Lan W, Sun W, Dai Q, Xiong Y, Li L et al. 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(8):2081-2086.
  • Gunning-Dixon FM, Raz N. The cognitive correlates of white matter abnormalities in normal aging: a quantitative review. Neuropsychology. 2000;14(2):224.
  • Arnold R, Issar T, Krishnan AV, Pussell BA. Neurological complications in chronic kidney disease. JRSM Cardiovasc Dis. 2016;5:2048004016677687.
  • Liu M, Wu Y, Wu X, Ma X, Yin Y, Fang H, et al. White Matter Microstructure Changes and Cognitive Impairment in the Progression of Chronic Kidney Disease. Front Neurosci. 2020;14:559117.

Kronik Böbrek Hastalığına Merkezi Sinir Sistemi Cevabı

Year 2022, Volume: 17 Issue: 3, 198 - 209, 02.11.2022

Güray Okyar Dursun Alper Yılmaz Mehmet Salih Yıldırım Metin Yıldız

https://doi.org/10.17517/ksutfd.917658

Abstract

Özet
İnsan nüfusunun yaşlanması nedeniyle kronik böbrek hastalığı (KBH) gibi hastalıkların prevalansı her geçen yıl artmaktadır. Kronik böbrek hastalığı, böbrek yapı ve işlevini etkileyen heterojen bozuklukları ifade eden genel bir terimdir. Glomerüler filtrasyonda azalmayı takriben böbreğin sıvı-solüt dengesini ayarlama yeteneğinde, metabolik ve endokrin fonksiyonlarında kronik ve progresif bozulma durumu olarak tanımlanabilmektedir. KBH sıklıkla yaşlıları etkilemektedir. Yaşın ilerlemesiyle birlikte böbreklerde birtakım yapısal ve fonksiyonel değişiklikler ortaya çıkar. Dolayısıyla, gelecekte hafif ve orta dereceli KBH’dan muzdarip hasta sayısının artması beklenmektedir. KBH, kalp ve beyin gibi diğer organlara zarar veren derin metabolik ve hemodinamik değişikliklere yol
açar. Merkezi sinir sistemi anormallikleri ve bilişsel eksiklik, KBH’nın şiddeti ile ilerlemekte ve çoğunlukla hemodiyaliz hastaları arasında ortaya çıkmaktadır. Ayrıca bireyleri sosyo-ekonomik yönden de etkilemektedir. Hastalarda KBH risk faktörlerinin erken tanınması temel noktayı oluşturmaktadır. Bu nedenle, risk altındaki gruplarda uygulanacak olası önleyici ve koruyucu tedavilerin tespiti ve hastalığın tedavisi için bu mekanizmaların incelenmesi gerekmektedir. Bu derleme, ilgili mekanizmalar hakkında mevcut bilgileri sunmaktadır.

Keywords

Fonksiyonel beyin değişiklikleri Nörobilişsel yetenek Renal replasman yöntemleri

References

  • 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. Nephrology Dialysis Transplantation. 2015;30(7):1162-1169.
  • Brück K, Stel VS, Gambaro G, Hallan S, Völzke H, Ärnlöv J et al. CKD prevalence varies across the European general population. Journal of the American Society of Nephrology. 2016;27(7):2135-2147.
  • Hill NR, Fatoba ST, Oke JL, Hirst JA, O’Callaghan CA, Lasserson DS et al. Global prevalence of chronic kidney disease–A systematic review and meta-analysis. PloS one. 2016;11(7):e0158765.
  • Tanrıverdi MH. Kronik böbrek yetmezliği. Konuralp Tıp Dergisi. 2010;2(2):27-32.
  • Rothwell P, Coull A, Giles M, Howard S, Silver L, Bull L et al. Change in stroke incidence, mortality, case-fatality, severity, and risk factors in Oxfordshire, UK from 1981 to 2004 (Oxford Vascular Study). The Lancet. 2004;363(9425):1925-1933.
  • El Husseini N, Kaskar O, Goldstein LB. Chronic kidney disease and stroke. Advances in chronic kidney disease. 2014;21(6):500-508.
  • Reinecke H, Brand E, Mesters R, Schäbitz W-R, Fisher M, Pavenstädt H et al. Dilemmas in the management of atrial fibrillation in chronic kidney disease. Journal of the American Society of Nephrology. 2009;20(4):705-711.
  • Hamed SA. Neurologic conditions and disorders of uremic syndrome of chronic kidney disease: Presentations, causes, and treatment strategies. Expert Rev Clin Pharmacol. 2019;12(1):61-90.
  • Seifter JL, Samuels MA. Uremic encephalopathy and other brain disorders associated with renal failure. Seminars in neurology. 2011;31(2):139-143.
  • McQuillan R, Jassal SV. Neuropsychiatric complications of chronic kidney disease. Nature Reviews Nephrology. 2010;6(8):471.
  • Brouns R, De Deyn P. Neurological complications in renal failure: A review. Clinical neurology and neurosurgery. 2004;107(1):1-16.
  • Malyszko J. Mechanism of endothelial dysfunction in chronic kidney disease. Clinica chimica acta. 2010;411(19-20):1412-1420.
  • Arnold R, Issar T, Krishnan AV, Pussell BA. Neurological complications in chronic kidney disease. JRSM cardiovascular disease. 2016;5:2048004016677687.
  • Fazekas G, Fazekas F, Schmidt R, Kapeller P, Offenbacher H, Krejs GJ. Brain MRI findings and cognitive impairment in patients undergoing chronic hemodialysis treatment. Journal of the neurological sciences. 1995;134(1-2):83-88.
  • Varela FJ. Patterns of life: Intertwining identity and cognition. Brain and cognition. 1997;34(1):72-87.
  • Mistry K. Dialysis disequilibrium syndrome prevention and management. International journal of nephrology and renovascular disease. 2019;12:69.
  • Nakai S, Wakai K, Kanda E, Kawaguchi K, Sakai K, Kitaguchi N. Is hemodialysis itself a risk factor for dementia? An analysis of nationwide registry data of patients on maintenance hemodialysis in Japan. Renal Replacement Therapy. 2018;4(1):12.
  • van Zwieten A, Wong G, Ruospo M, Palmer SC, Barulli MR, Iurillo A et al. Prevalence and patterns of cognitive impairment in adult hemodialysis patients: the COGNITIVE-HD study. Nephrology Dialysis Transplantation. 2018;33(7):1197-1206.
  • Etgen T, Chonchol M, Förstl H, Sander D. Chronic kidney disease and cognitive impairment: A systematic review and meta-analysis. American journal of nephrology. 2012;35(5):474-482.
  • Association AP. American Psychiatric Association DSM-5 Development. Proposed Revisions/Somatic Symptom Disorders/J. 2010;2.
  • Bevins EA, Peters J, Léger GC. The Diagnosis and Management of Reversible Dementia Syndromes. Current Treatment Options in Neurology. 2021;23(1):1-13.
  • Hugo J, Ganguli M. Dementia and cognitive impairment: epidemiology, diagnosis, and treatment. Clinics in geriatric medicine. 2014;30(3):421-442.
  • Fratiglioni L, Qiu C. Prevention of cognitive decline in ageing: dementia as the target, delayed onset as the goal. The Lancet Neurology. 2011;10(9):778-779.
  • Viggiano D, Wagner CA, Martino G, Nedergaard M, Zoccali C, Unwin R et al. Mechanisms of cognitive dysfunction in CKD. Nature Reviews Nephrology. 2020;16(8):452-469.
  • Zammit AR, Katz MJ, Zimmerman ME, Bitzer M, Lipton RB. Low eGFR is associated with dysexecutive and amnestic mild cognitive impairment. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring. 2015;1(2):152-159.
  • Elias MF, Elias PK, Seliger SL, Narsipur SS, Dore GA, Robbins MA. Chronic kidney disease, creatinine and cognitive functioning. Nephrology Dialysis Transplantation. 2009;24(8):2446-2452.
  • Hung P-H, Yeh C-C, Hsiao C-Y, Sung P-S, Muo C-H, Sung F-C et al. End stage renal disease is associated with development of dementia. Oncotarget. 2017;8(64):107348.
  • Seyahi N, Ates K, Suleymanlar G. Türkiye’de Renal Replasman Tedavilerinin Güncel Durumu: Türk Nefroloji Derneği Kayıt Sistemi 2016 Yılı Özet Raporu Current Status of Renal Replacement Therapies in Turkey: Turkish Society of Nephrology Registry 2016 Summary Report. 2018.
  • Ozcan H, Yucel A, Avşar U, Çankaya 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. Transplantation proceedings; 2015;47(5):1348-1351.
  • Tomlinson JA, Wheeler DC. The role of trimethylamine N-oxide as a mediator of cardiovascular complications in chronic kidney disease. Kidney international. 2017;92(4):809-815.
  • Busch M, Fleck C, Wolf G, Stein G. Asymmetrical (ADMA) and symmetrical dimethylarginine (SDMA) as potential risk factors for cardiovascular and renal outcome in chronic kidney disease–possible candidates for paradoxical epidemiology? Amino Acids. 2006;30(3):225-232.
  • Gryp T, Vanholder R, Vaneechoutte M, Glorieux G. p-Cresyl sulfate. Toxins. 2017;9(2):52.
  • Barreto FC, Barreto DV, Liabeuf S, Meert N, Glorieux G, Temmar M et al. Serum indoxyl sulfate is associated with vascular disease and mortality in chronic kidney disease patients. Clinical Journal of the American Society of Nephrology. 2009;4(10):1551-1558.
  • Zhang D-L, Liu J, Liu S, Zhang Y, Liu W-H. The differences of asymmetric dimethylarginine removal by different dialysis treatments. Renal failure. 2010;32(8):935-940.
  • Watanabe K, Watanabe T, Nakayama M. Cerebro-renal interactions: impact of uremic toxins on cognitive function. Neurotoxicology. 2014;44:184-193.
  • Lameire N, Vanholder R, De Smet R. Uremic toxins and peritoneal dialysis. Kidney Int Suppl. 2001;78:292-297.
  • Krieter DH, Hackl A, Rodriguez A, Chenine L, Moragues HL, Lemke H-D et al. Protein-bound uraemic toxin removal in haemodialysis and post-dilution haemodiafiltration. Nephrology Dialysis Transplantation. 2010;25(1):212-218.
  • Thornalley PJ. Glycation free adduct accumulation in renal disease: the new AGE. Pediatric Nephrology. 2005;20(11):1515-1522.
  • Mathew AT, Fishbane S, Obi Y, Kalantar-Zadeh K. Preservation of residual kidney function in hemodialysis patients: reviving an old concept. Kidney international. 2016;90(2):262-271.
  • Simões-Silva L, Araujo R, Pestana M, Soares-Silva I, Sampaio-Maia B. The microbiome in chronic kidney disease patients undergoing hemodialysis and peritoneal dialysis. Pharmacological research. 2018;130:143-151.
  • McIntyre CW, Salerno FR. Diagnosis and treatment of intradialytic hypotension in maintenance hemodialysis patients. Clinical Journal of the American Society of Nephrology. 2018;13(3):486-489.
  • Finnerty FA, Witkin L, Fazekas JF. Cerebral hemodynamics during cerebral ischemia induced by acute hypotension. The Journal of clinical investigation. 1954;33(9):1227-1232.
  • Fukunishi I, Kitaoka T, Shirai T, Kino K, Kanematsu E, Sato Y. Psychiatric disorders among patients undergoing hemodialysis therapy. Nephron. 2002;91(2):344-347.
  • Tamura MK, Yaffe K. Dementia and cognitive impairment in ESRD: diagnostic and therapeutic strategies. Kidney international. 2011;79(1):14-22.
  • Murray AM. Cognitive impairment in the aging dialysis and chronic kidney disease populations: an occult burden. Advances in chronic kidney disease. 2008;15(2):123-132.
  • Posselt J, Harbeck B, Rahvar AH, Kropp P, Haas CS. Improved cognitive function after kidney transplantation compared to hemodialysis. Ther Apher Dial. 2021;25(6):931-938.
  • Simpson IA, Carruthers A, Vannucci SJ. Supply and demand in cerebral energy metabolism: the role of nutrient transporters. J Cereb Blood Flow Metab. 2007;27(11):1766-1791.
  • Villringer A, Planck J, Hock C, Schleinkofer L, Dirnagl U. Near infrared spectroscopy (NIRS): a new tool to study hemodynamic changes during activation of brain function in human adults. Neuroscience letters. 1993;154(1-2):101-104.
  • Takahashi T, Shirane R, Sato S, Yoshimoto T. Developmental changes of cerebral blood flow and oxygen metabolism in children. American journal of neuroradiology. 1999;20(5):917-922.
  • Lassen N, Munck O. The cerebral blood flow in man determined by the use of radioactive krypton. Acta Physiologica Scandinavica. 1955;33(1):30-49.
  • Chen JJ, Rosas HD, Salat DH. Age-associated reductions in cerebral blood flow are independent from regional atrophy. Neuroimage. 2011;55(2):468-478.
  • Zauner A, Muizelaar JP. Brain metabolism and cerebral blood flow. Head injury. 1997:89-99.
  • Muller M, van der Graaf Y, Visseren FL, Vlek AL, Mali WP, Geerlings MI et al. Blood pressure, cerebral blood flow, and brain volumes. The SMART-MR study. Journal of hypertension. 2010;28(7):1498-1505.
  • Lee C, Lopez OL, Becker JT, Raji C, Dai W, Kuller LH et al. Imaging cerebral blood flow in the cognitively normal aging brain with arterial spin labeling: implications for imaging of neurodegenerative disease. Journal of Neuroimaging. 2009;19(4):344-352.
  • Lu H, Xu F, Rodrigue KM, Kennedy KM, Cheng Y, Flicker B, et al. Alterations in cerebral metabolic rate and blood supply across the adult lifespan. Cerebral cortex. 2011;21(6):1426-1434.
  • Malik J, Kudlicka J, Lachmanova J, Valerianova A, Rocinova K, Bartkova M et al. Tissue ischemia worsens during hemodialysis in end-stage renal disease patients. The journal of vascular access. 2017;18(1):47-51.
  • Prohovnik I, Post J, Uribarri J, Lee H, Sandu O, Langhoff E. Cerebrovascular effects of hemodialysis in chronic kidney disease. Journal of Cerebral Blood Flow & Metabolism. 2007;27(11):1861-1869.
  • Ito K, Ookawara S, Ueda Y, Goto S, Miyazawa H, Yamada H et al. Factors affecting cerebral oxygenation in hemodialysis patients: cerebral oxygenation associates with pH, hemodialysis duration, serum albumin concentration, and diabetes mellitus. PLoS One. 2015;10(2):e0117474.
  • Hoshino T, Ookawara S, Goto S, Miyazawa H, Ito K, Ueda Y, et al. Evaluation of cerebral oxygenation in patients undergoing long-term hemodialysis. Nephron Clinical Practice. 2014;126(1):57-61.
  • Ookawara S, Ito K, Sasabuchi Y, Ueda Y, Hayasaka H, Kofuji M et al. Association between Cerebral Oxygenation, as Evaluated with Near-Infrared Spectroscopy, and Cognitive Function in Patients Undergoing Hemodialysis. Nephron. 2021:1-8.
  • Regolisti G, Maggiore U, Cademartiri C, Cabassi A, Caiazza A, Tedeschi S, et al. Cerebral blood flow decreases during intermittent hemodialysis in patients with acute kidney injury, but not in patients with end-stage renal disease. Nephrology Dialysis Transplantation. 2013;28(1):79-85.
  • Minato S, Ookawara S, Ito K, Hayasaka H, Kofuji M, Uchida T, et al. Continuous monitoring of changes in cerebral oxygenation during hemodialysis in a patient with acute congestive heart failure. Journal of Artificial Organs. 2019:1-4.
  • Yoon S, Zuccarello M, Rapoport RM. pCO2 and pH regulation of cerebral blood flow. Frontiers in physiology. 2012;3:365.
  • Tamura MK, Pajewski NM, Bryan RN, Weiner DE, Diamond M, Van Buren P et al. Chronic kidney disease, cerebral blood flow, and white matter volume in hypertensive adults. Neurology. 2016;86(13):1208-1216.
  • Jiang XL, Wen JQ, Zhang LJ, Zheng G, Li X, Zhang Z et al. Cerebral blood flow changes in hemodialysis and peritoneal dialysis patients: an arterial-spin labeling MR imaging. Metabolic brain disease. 2016;31(4):929-936.
  • Hirakata H, Yao H, Osato S, Ibayashi S, Onoyama K, Otsuka M et al. CBF and oxygen metabolism in hemodialysis patients: effects of anemia correction with recombinant human EPO. American Journal of Physiology-Renal Physiology. 1992;262(5):737-743.
  • Nanba T, Ogasawara K, Nishimoto H, Fujiwara S, Kuroda H, Sasaki M et al. Postoperative cerebral white matter damage associated with cerebral hyperperfusion and cognitive impairment after carotid endarterectomy: a diffusion tensor magnetic resonance imaging study. Cerebrovascular Diseases. 2012;34(5-6):358-367.
  • Rink C, Khanna S. Significance of brain tissue oxygenation and the arachidonic acid cascade in stroke. Antioxidants & redox signaling. 2011;14(10):1889-1903.
  • Yılmaz N. Kan-Beyin bariyerinin fizyopatolojisi. Van Tıp Dergisi. 2006;13(1):25-7.
  • Stamatovic SM, Keep RF, Andjelkovic AV. Brain endothelial cell-cell junctions: How to "open" the blood brain barrier. Curr Neuropharmacol. 2008;6(3):179-92.
  • Köksel T, Güleryüz A. Kan-Beyin Bariyeri. Mersin Üniversitesi Tip Fakültesi Dergisi. 2012;2(1):94-99.
  • Pardridge WM. Brain metabolism: A perspective from the blood-brain barrier. Physiological reviews. 1983;63(4):1481-1535.
  • Yilmaz O, Taskiran D. Astrosit Hücre Kültürlerinde pH Değişikliğinin Yarattığı Toksisite ve Glutatyonun Koruyucu Etkisi. Journal of Neurological Sciences. 2010;27(1):61-68.
  • Bell AH, Miller SL, Castillo-Melendez M, Malhotra A. The neurovascular unit: effects of brain insults during the perinatal period. Frontiers in neuroscience. 2020;13:1452.
  • Haluska M, Anthony ML. Osmotic blood-brain barrier modification for the treatment of malignant brain tumors. Clinical journal of oncology nursing. 2004;8(3):263-267.
  • 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. Scientific reports. 2019;9(1):1-22.
  • 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. American journal of translational research. 2018;10(7):2137.
  • Lau WL, Nunes AC, Vasilevko V, Floriolli D, Lertpanit L, Savoj J et al. Chronic kidney disease increases cerebral microbleeds in mouse and man. Translational stroke research. 2020;11(1):122-134.
  • MacKenzie ET, Strandgaard S, Graham DI, Jones JV, Harper AM, Farrar JK. Effects of acutely induced hypertension in cats on pial arteriolar caliber, local cerebral blood flow, and the blood-brain barrier. Circulation research. 1976;39(1):33-41.
  • Horani MH, Mooradian AD. Effect of diabetes on the blood brain barrier. Current pharmaceutical design. 2003;9(10):833-840.
  • Banks W, Farr S, Salameh T, Niehoff M, Rhea E, Morley J et al. Triglycerides cross the blood–brain barrier and induce central leptin and insulin receptor resistance. International journal of obesity. 2018;42(3):391-397.
  • Jin M, Wang L, Wang H, Han X, Diao Z, Guo W et al. Disturbed neurovascular coupling in hemodialysis patients. PeerJ. 2020;8:e8989.
  • Soto-Rojas LO, Pacheco-Herrero M, Martínez-Gómez PA, Campa-Córdoba B, Apátiga-Pérez R, Villegas-Rojas MM, et al. The Neurovascular Unit Dysfunction in Alzheimer’s Disease. International Journal of Molecular Sciences. 2021;22(4):2022.
  • 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(4):478-485.
  • De Deyn PP, Vanholder R, Eloot S, Glorieux G. Progress in uremic toxin research: Guanidino compounds as uremic (neuro) toxins. Seminars in dialysis; 2009:22(4):340-345.
  • Ohno K, Ito M, Ichihara M, Ito M. Molecular hydrogen as an emerging therapeutic medical gas for neurodegenerative and other diseases. Oxidative medicine and cellular longevity. 2012;2012:353152.
  • Baranyi A, Amouzadeh-Ghadikolai O, Von Lewinski D, Breitenecker RJ, Stojakovic T, März W et al. Beta-trace protein as a new non-invasive immunological marker for quinolinic acid-induced impaired blood-brain barrier integrity. Scientific reports. 2017;7(1):1-8.
  • Lester D. The concentration of neurotransmitter metabolites in the cerebrospinal fluid of suicidal individuals: a meta-analysis. Pharmacopsychiatry. 1995;28(02):45-50.
  • Kidwell CS, Chalela JA, Saver JL, Starkman S, Hill MD, Demchuk AM et al. Comparison of MRI and CT for detection of acute intracerebral hemorrhage. Jama. 2004;292(15):1823-1830.
  • Freedman BI, Sink KM, Hugenschmidt CE, Hughes TM, Williamson JD, Whitlow CT et al. Associations of early kidney disease with brain magnetic resonance imaging and cognitive function in African Americans with type 2 diabetes mellitus. American Journal of Kidney Diseases. 2017;70(5):627-637.
  • Solomon MA, van der Plas E, Langbehn KE, Novak M, Schultz JL, Koscik TR et al. Early pediatric chronic kidney disease is associated with brain volumetric gray matter abnormalities. Pediatric Research. 2020:1-7.
  • Sedaghat S, Cremers LG, De Groot M, Hoorn EJ, Hofman A, Van Der Lugt A et al. Kidney function and microstructural integrity of brain white matter. Neurology. 2015;85(2):154-161.
  • Borgwardt SJ, Riecher-Rössler A, Dazzan P, Chitnis X, Aston J, Drewe M et al. Regional gray matter volume abnormalities in the at risk mental state. Biological psychiatry. 2007;61(10):1148-1156.
  • Hsieh T-J, Chang J-M, Chuang H-Y, Ko C-H, Hsieh M-L, Liu G-C et al. End-stage renal disease: in vivo diffusion-tensor imaging of silent white matter damage. Radiology. 2009;252(2):518-525.
  • Mu J, Chen T, Li P, Ding D, Ma X, Zhang M et al. Altered white matter microstructure mediates the relationship between hemoglobin levels and cognitive control deficits in end‐stage renal disease patients. Human brain mapping. 2018;39(12):4766-4775.
  • Shima H, Ishimura E, Naganuma T, Ichii M, Yamasaki T, Mori K et al. Decreased kidney function is a significant factor associated with silent cerebral infarction and periventricular hyperintensities. Kidney and Blood Pressure Research. 2011;34(6):430-438.
  • Kobayashi M, Hirawa N, Yatsu K, Kobayashi Y, Yamamoto Y, Saka S et al. Relationship between silent brain infarction and chronic kidney disease. Nephrology Dialysis Transplantation. 2009;24(1):201-207.
  • Yao H, Araki Y, Takashima Y, Uchino A, Yuzuriha T, Hashimoto M. Chronic kidney disease and subclinical brain infarction increase the risk of vascular cognitive impairment: The Sefuri study. Journal of Stroke and Cerebrovascular Diseases. 2017;26(2):420-424.
  • 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. Journal of the neurological sciences. 2016;362:1-6.
  • Ovbiagele B, Wing JJ, Menon RS, Burgess RE, Gibbons MC, Sobotka I et al. Association of chronic kidney disease with cerebral microbleeds in patients with primary intracerebral hemorrhage. Stroke. 2013;44(9):2409-2413.
  • Xiao L, Lan W, Sun W, Dai Q, Xiong Y, Li L et al. 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(8):2081-2086.
  • Gunning-Dixon FM, Raz N. The cognitive correlates of white matter abnormalities in normal aging: a quantitative review. Neuropsychology. 2000;14(2):224.
  • Arnold R, Issar T, Krishnan AV, Pussell BA. Neurological complications in chronic kidney disease. JRSM Cardiovasc Dis. 2016;5:2048004016677687.
  • Liu M, Wu Y, Wu X, Ma X, Yin Y, Fang H, et al. White Matter Microstructure Changes and Cognitive Impairment in the Progression of Chronic Kidney Disease. Front Neurosci. 2020;14:559117.
There are 104 citations in total.

Details

Primary Language Turkish
Subjects Health Care Administration
Journal Section Derlemeler
Authors

Güray Okyar 0000-0002-9618-9279

Dursun Alper Yılmaz 0000-0001-8096-5504

Mehmet Salih Yıldırım 0000-0003-2632-4583

Metin Yıldız 0000-0003-0122-5677

Early Pub Date November 1, 2022
Publication Date November 2, 2022
Submission Date April 16, 2021
Acceptance Date May 5, 2021
Published in Issue Year 2022 Volume: 17 Issue: 3

Cite

AMA Okyar G, Yılmaz DA, Yıldırım MS, Yıldız M. Kronik Böbrek Hastalığına Merkezi Sinir Sistemi Cevabı. KSU Medical Journal. November 2022;17(3):198-209. doi:10.17517/ksutfd.917658
 Download Cover Image