{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T23:25:33Z","timestamp":1791329133202,"version":"4.3.1"},"reference-count":82,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:p>Approximately 40% of patients with chronic kidney disease (CKD) experience cognitive impairment (CI), which is strongly associated with increased mortality. CI is driven by multiple factors, including vascular injury, accumulation of uremic toxins, disruption of the blood\u2013brain barrier, and chronic inflammation. Recent evidence suggests that kidney disease and neurocognitive decline are mechanistically linked through dysregulated tryptophan metabolism. Tryptophan is metabolised through three main pathways: the kynurenine, indole, and serotonin pathways, each producing bioactive metabolites with distinct neurophysiological effects. The hallmarks of CKD include chronic inflammation, gut microbial dysbiosis, and impaired renal clearance, all of which alter tryptophan metabolism. Inflammation drives tryptophan metabolism towards the kynurenine pathway, increasing the formation of neurotoxic compounds that promote oxidative stress, excitotoxicity, and neuronal injury. However, reduced availability of tryptophan for serotonin synthesis impairs serotonergic signalling and neurotransmission, as well as melatonin biosynthesis, thereby contributing to circadian rhythm disturbances and impaired glymphatic clearance. Concurrently, gut dysbiosis and reduced renal clearance promote the accumulation of indole-derived uremic toxins, leading to endothelial dysfunction, neuroinflammation, and disruption of the blood\u2013brain barrier. This review highlights the current evidence of dysregulated tryptophan metabolism in CKD and its impact on the pathogenesis of neurocognitive complications. The review also discusses potential biomarkers and therapeutic strategies, including kynurenine pathway inhibitors, gut microbiota modulation, uremic toxin adsorption, melatonin supplementation and personalised medicine to mitigate cognitive impairment in CKD.<\/jats:p>","DOI":"10.3389\/fnins.2026.1872778","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T05:45:02Z","timestamp":1784267102000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Altered tryptophan metabolism as a contributor to cognitive impairment in chronic kidney disease: a narrative review"],"prefix":"10.3389","volume":"20","author":[{"given":"Harish","family":"Selvaraj","sequence":"first","affiliation":[{"name":"Division of Medical Research, SRM Medical College Hospital and Research Centre, SRMIST","place":["Chengalpattu, Tamil Nadu, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Varadharajan","family":"Jayaprakash","sequence":"additional","affiliation":[{"name":"Department of Nephrology, SRM Medical College Hospital and Research Centre, SRMIST","place":["Chengalpattu, Tamil Nadu, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janardanan Subramonia","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of General Medicine, SRM Medical College Hospital and Research Centre, SRMIST","place":["Chengalpattu, Tamil Nadu, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerry George","family":"Mathew","sequence":"additional","affiliation":[{"name":"Department of Nephrology, SRM Medical College Hospital and Research Centre, SRMIST","place":["Chengalpattu, Tamil Nadu, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karthikeyan","family":"Sundaram","sequence":"additional","affiliation":[{"name":"Department of Herbal Pharmacology and Environmental Sustainability, Chettinad Hospital and Research Institute, Chettinad Academy of Research and Education","place":["Kelambakkam, Tamil Nadu, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Venkataraman","family":"Prabhu","sequence":"additional","affiliation":[{"name":"Division of Medical Research, SRM Medical College Hospital and Research Centre, SRMIST","place":["Chengalpattu, Tamil Nadu, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,17]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"370","DOI":"10.3389\/fphar.2017.00370","article-title":"Indoxyl sulfate affects glial function increasing oxidative stress and neuroinflammation in chronic kidney disease: interaction between astrocytes and microglia","volume":"8","author":"Adesso","year":"2017","journal-title":"Front. Pharmacol."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1027","DOI":"10.1016\/j.bcp.2012.12.014","article-title":"Kynurenic acid as an antagonist of \u03b17 nicotinic acetylcholine receptors in the brain: facts and challenges","volume":"85","author":"Albuquerque","year":"2013","journal-title":"Biochem. Pharmacol."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"544","DOI":"10.3390\/toxins16120544","article-title":"The ability of AST-120 to lower the serum Indoxyl sulfate level improves renal outcomes and the lipid profile in diabetic and nondiabetic animal models of chronic kidney disease: a meta-analysis","volume":"16","author":"Altunkaynak","year":"2024","journal-title":"Toxins"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1590\/2175-8239-JBN-2018-0086","article-title":"Montreal cognitive assessment for cognitive assessment in chronic kidney disease: a systematic review","volume":"41","author":"Amatneeks","year":"2019","journal-title":"J. Bras. Nefrol."},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1177\/1178646917691938","article-title":"Kynurenine pathway of tryptophan metabolism: regulatory and functional aspects","volume":"10","author":"Badawy","year":"2017","journal-title":"Int. J. Tryptophan Res."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"e038711","DOI":"10.1161\/JAHA.124.038711","article-title":"Associations of cerebral small vessel disease and chronic kidney disease in patients with acute ischemic stroke","volume":"14","author":"Bi","year":"2025","journal-title":"J. Am. Heart Assoc."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1016\/S0140-6736(20)30045-3","article-title":"Global, regional, and national burden of chronic kidney disease, 1990\u20132017: a systematic analysis for the global burden of disease study 2017","volume":"395","author":"Bikbov","year":"2020","journal-title":"Lancet"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1684\/ndt.2023.51","article-title":"Cognitive impairment and the blood-brain barrier in chronic kidney disease: role of the uremic toxins","volume":"19","author":"Bobot","year":"2023","journal-title":"Nephrol. Therap."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"1509","DOI":"10.1681\/ASN.2019070728","article-title":"Uremic toxic blood-brain barrier disruption mediated by AhR activation leads to cognitive impairment during experimental renal dysfunction","volume":"31","author":"Bobot","year":"2020","journal-title":"J Am Soc Nephrol"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"sfae294","DOI":"10.1093\/ckj\/sfae294","article-title":"Cognitive impairment in CKD patients: a guidance document by the CONNECT network","volume":"18","author":"Bolignano","year":"2025","journal-title":"Clin. Kidney J."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1002\/jcsm.12874","article-title":"Effects of AST-120 on muscle health and quality of life in chronic kidney disease patients: results of RECOVERY study","volume":"13","author":"Cha","year":"2022","journal-title":"J. Cachexia. Sarcopenia Muscle"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.3390\/toxins12110684","article-title":"Indoxyl sulfate, a tubular toxin, contributes to the development of chronic kidney disease","volume":"12","author":"Cheng","year":"2020","journal-title":"Toxins"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"H135","DOI":"10.1152\/ajpheart.00908.2024","article-title":"Endothelial dysfunction in chronic kidney disease: a clinical perspective","volume":"329","author":"Cho","year":"2025","journal-title":"Am. J. Phys. Heart Circ. Phys."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"782199","DOI":"10.3389\/fphar.2022.782199","article-title":"Aryl hydrocarbon receptor mechanisms affecting chronic kidney disease","volume":"13","author":"Curran","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.3390\/toxins12060412","article-title":"How do uremic toxins affect the endothelium?","volume":"12","author":"Cunha","year":"2020","journal-title":"Toxins"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"362","DOI":"10.3389\/fncel.2014.00362","article-title":"The impact of microglial activation on blood-brain barrier in brain diseases","volume":"8","author":"da Fonseca","year":"2014","journal-title":"Front. Cell. Neurosci."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"1178646917694600","DOI":"10.1177\/1178646917694600","article-title":"Tryptophan metabolism in patients with chronic kidney disease secondary to type 2 diabetes: relationship to inflammatory markers","volume":"10","author":"Debnath","year":"2017","journal-title":"Int. J. Tryptophan Res."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"782","DOI":"10.1053\/j.ajkd.2019.05.017","article-title":"Cognitive impairment in CKD: pathophysiology, management, and prevention","volume":"74","author":"Drew","year":"2019","journal-title":"Am. J. Kidney Dis."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1038\/s41581-024-00820-6","article-title":"Chronic kidney disease and the global public health agenda: an international consensus","volume":"20","author":"Francis","year":"2024","journal-title":"Nat. Rev. Nephrol."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1590\/2175-8239-JBN-2018-0033","article-title":"The specific impact of uremic toxins upon cognitive domains: a review","volume":"41","author":"Franco","year":"2019","journal-title":"J. Bras. Nefrol."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"e17238","DOI":"10.34172\/JNP.2022.17238","article-title":"Platelet glycogen synthase kinase 3\u03b2 regulates plasma \u03b2 amyloid and phosphorylated tau levels in chronic kidney disease patients with cognitive dysfunction; therapeutic role of erythropoietin","volume":"12","author":"Ganesan","year":"2021","journal-title":"J. Nephropathol."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1007\/s40520-023-02645-y","article-title":"Analysis of intestinal flora and cognitive function in maintenance hemodialysis patients using combined 16S ribosome DNA and shotgun metagenome sequencing","volume":"36","author":"Gao","year":"2024","journal-title":"Aging Clin. Exp. Res."},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1093\/ckj\/sfaf380","article-title":"Untangling amino acid metabolism in renal diseases: mechanisms, dysregulation, and critical gaps","volume":"19","author":"Heneberg","year":"2026","journal-title":"Clin. Kidney J."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"158","DOI":"10.3389\/fendo.2019.00158","article-title":"Tryptophan metabolic pathways and brain serotonergic activity: a comparative review","volume":"10","author":"H\u00f6glund","year":"2019","journal-title":"Front. Endocrinol."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"1736","DOI":"10.7150\/ijms.109245","article-title":"Indoxyl sulfate is associated with cognitive impairment in ESRD patients by activating the extrinsic apoptosis in the neuronal cells during differentiating process","volume":"22","author":"Hsieh","year":"2025","journal-title":"Int. J. Med. Sci."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"ii4","DOI":"10.1093\/ndt\/gfab216","article-title":"Acidosis, cognitive dysfunction and motor impairments in patients with kidney disease","volume":"37","author":"Imenez Silva","year":"2021","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.sleep.2023.09.011","article-title":"The effect of melatonin on sleep quality and cognitive function of individuals undergoing hemodialysis","volume":"111","author":"Jafari","year":"2023","journal-title":"Sleep Med."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"1048","DOI":"10.1016\/j.kint.2019.07.012","article-title":"A single number for advocacy and communication-worldwide more than 850 million individuals have kidney diseases","volume":"96","author":"Jager","year":"2019","journal-title":"Kidney Int."},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.3390\/ijms242417557","article-title":"Trimethylamine N-oxide as a mediator linking peripheral to central inflammation: an in vitro study","volume":"24","author":"Janeiro","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"374","DOI":"10.15171\/apb.2019.044","article-title":"5-HIAA as a potential biological marker for neurological and psychiatric disorders","volume":"9","author":"Jayamohananan","year":"2019","journal-title":"Adv. Pharm. Bull."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"774","DOI":"10.23876\/j.krcp.23.005","article-title":"Indoxyl sulfate induces apoptotic cell death by inhibiting glycolysis in human astrocytes","volume":"43","author":"Jeong","year":"2024","journal-title":"Kidney Res. Clinic. Pract."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"1600","DOI":"10.1007\/s11307-020-01501-z","article-title":"A multi-ligand imaging study exploring GABAergic receptor expression and inflammation in multiple sclerosis","volume":"22","author":"Kang","year":"2020","journal-title":"Mol. Imaging Biol."},{"key":"ref34","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2024.1524651","article-title":"Targeting the kynurenine pathway: another therapeutic opportunity in the metabolic crosstalk between cancer and immune cells","volume":"14","author":"Kang","year":"2025","journal-title":"Front. Oncol."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"4837","DOI":"10.3390\/ijms22094837","article-title":"Serotonin\u2014its synthesis and roles in the healthy and the critically ill","volume":"22","author":"Kanova","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1186\/s12882-016-0387-3","article-title":"Tryptophan metabolism, its relation to inflammation and stress markers and association with psychological and cognitive functioning: Tasmanian chronic kidney disease pilot study","volume":"17","author":"Karu","year":"2016","journal-title":"BMC Nephrol."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"374","DOI":"10.32794\/mr112500137","article-title":"Serotonin, melatonin and their precursors and metabolites and vitamin D3 derivatives in honey","volume":"5","author":"Kim","year":"2022","journal-title":"Melatonin Res."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"1298432","DOI":"10.3389\/fmicb.2024.1298432","article-title":"Gut microbiota associations with chronic kidney disease: insights into nutritional and inflammatory parameters","volume":"15","author":"Lazarevic","year":"2024","journal-title":"Front. Microbiol."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"20250379","DOI":"10.1515\/tnsci-2025-0379","article-title":"The role of melatonin in affecting cognitive dysfunction in acute sleep deprivation mice through the nuclear factor kappaB pathway and oxidative stress","volume":"16","author":"Li","year":"2025","journal-title":"Transl. Neurosci."},{"key":"ref40","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.769501","article-title":"New insights into gut-Bacteria-derived indole and its derivatives in intestinal and liver diseases","volume":"12","author":"Li","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"e16438","DOI":"10.1111\/ene.16438","article-title":"Endothelium-related biomarkers and cognitive decline in prevalent hemodialysis patients: a prospective cohort study","volume":"31","author":"Lib\u00f3rio","year":"2024","journal-title":"Eur. J. Neurol."},{"key":"ref42","doi-asserted-by":"publisher","DOI":"10.3390\/toxins13020142","article-title":"Uremic toxins in the progression of chronic kidney disease and cardiovascular disease: mechanisms and therapeutic targets","volume":"13","author":"Lim","year":"2021","journal-title":"Toxins"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.neuro.2019.02.019","article-title":"Indole-3 acetic acid increased risk of impaired cognitive function in patients receiving hemodialysis","volume":"73","author":"Lin","year":"2019","journal-title":"Neurotoxicology"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1186\/s13045-018-0644-y","article-title":"Targeting the IDO1 pathway in cancer: from bench to bedside","volume":"11","author":"Liu","year":"2018","journal-title":"J. Hematol. Oncol."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"936","DOI":"10.3390\/antiox10060936","article-title":"Indoxyl-sulfate-induced redox imbalance in chronic kidney disease","volume":"10","author":"Lu","year":"2021","journal-title":"Antioxidants"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"e0321567","DOI":"10.1371\/journal.pone.0321567","article-title":"Efficacy of probiotics in patients with cognitive impairment: a systematic review and meta-analysis","volume":"20","author":"Ma","year":"2025","journal-title":"PLoS One"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/j.semnephrol.2014.02.010","article-title":"The kidney and uremic toxin removal: glomerulus or tubule?","volume":"34","author":"Masereeuw","year":"2014","journal-title":"Semin. Nephrol."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"224","DOI":"10.5527\/wjn.v5.i3.224","article-title":"Sleep disorders and chronic kidney disease","volume":"5","author":"Maung","year":"2016","journal-title":"World J. Nephrol."},{"key":"ref49","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1097\/MNH.0000000000001117","article-title":"Pathophysiology of cognitive impairment in chronic kidney disease","volume":"34","author":"Merlino","year":"2025","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"key":"ref50","doi-asserted-by":"publisher","first-page":"1603","DOI":"10.3390\/cells10071603","article-title":"Role of kynurenine pathway in oxidative stress during neurodegenerative disorders","volume":"10","author":"Mor","year":"2021","journal-title":"Cells"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"105529","DOI":"10.1016\/j.jstrokecerebrovasdis.2020.105529","article-title":"Chronic kidney disease and cognitive impairment","volume":"30","author":"Murtaza","year":"2021","journal-title":"J. Stroke Cerebrovasc. Dis."},{"key":"ref52","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.trsl.2016.04.007","article-title":"Gut microbiome in chronic kidney disease: challenges and opportunities","volume":"179","author":"Nallu","year":"2017","journal-title":"Transl. Res."},{"key":"ref53","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph19042389","article-title":"Cognitive impairment in end stage renal disease patients undergoing hemodialysis: markers and risk factors","volume":"19","author":"Olczyk","year":"2022","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"ref54","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1111\/cns.13768","article-title":"Kynurenic acid in neurodegenerative disorders-unique neuroprotection or double-edged sword?","volume":"28","author":"Ostapiuk","year":"2022","journal-title":"CNS Neurosci. Ther."},{"key":"ref55","doi-asserted-by":"publisher","first-page":"1339","DOI":"10.1007\/s00726-022-03161-5","article-title":"Microbiota-derived tryptophan metabolites in vascular inflammation and cardiovascular disease","volume":"54","author":"Paeslack","year":"2022","journal-title":"Amino Acids"},{"key":"ref56","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2016\/8952520","article-title":"Tryptophan biochemistry: structural, nutritional, metabolic, and medical aspects in humans","volume":"2016","author":"Palego","year":"2016","journal-title":"J. Amino Acids"},{"key":"ref57","doi-asserted-by":"publisher","first-page":"196","DOI":"10.2478\/v10039-010-0015-6","article-title":"Kynurenine pathway \u2013 a new link between endothelial dysfunction and carotid atherosclerosis in chronic kidney disease patients","volume":"55","author":"Pawlak","year":"2010","journal-title":"Adv. Med. Sci."},{"key":"ref58","doi-asserted-by":"publisher","first-page":"2899","DOI":"10.1111\/ene.15928","article-title":"Cognitive disorders in patients with chronic kidney disease: approaches to prevention and treatment","volume":"30","author":"P\u00e9pin","year":"2023","journal-title":"Eur. J. Neurol."},{"key":"ref59","doi-asserted-by":"publisher","first-page":"102","DOI":"10.4103\/PMRR.PMRR_94_24","article-title":"Risk factors of chronic kidney diseases: a retrospective, record based study from a tertiary Care Hospital in India","volume":"2","author":"Qureshi","year":"2025","journal-title":"Prevent. Med. Res. Rev."},{"key":"ref60","doi-asserted-by":"publisher","first-page":"652","DOI":"10.1100\/tsw.2005.86","article-title":"Probiotic amelioration of azotemia in 5\/6th nephrectomized Sprague-Dawley rats","volume":"5","author":"Ranganathan","year":"2005","journal-title":"Sci. World J."},{"key":"ref61","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.180229","article-title":"Quinolinic acid potentially links kidney injury to brain toxicity","volume":"10","author":"Saliba","year":"2025","journal-title":"JCI Insight"},{"key":"ref62","doi-asserted-by":"publisher","first-page":"1901","DOI":"10.1093\/ndt\/gfn739","article-title":"Increased indoleamine 2,3-dioxygenase (IDO) activity and elevated serum levels of tryptophan catabolites in patients with chronic kidney disease: a possible link between chronic inflammation and uraemic symptoms","volume":"24","author":"Schefold","year":"2009","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref63","doi-asserted-by":"publisher","first-page":"49","DOI":"10.2147\/IJNRD.S41339","article-title":"AST-120 for the management of progression of chronic kidney disease","volume":"7","author":"Schulman","year":"2014","journal-title":"Int. J. Nephrol. Renov. Dis."},{"key":"ref64","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1016\/j.kint.2016.09.040","article-title":"Probiotic supplementation in diabetic hemodialysis patients has beneficial metabolic effects","volume":"91","author":"Soleimani","year":"2017","journal-title":"Kidney Int."},{"key":"ref65","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1016\/j.neubiorev.2021.04.034","article-title":"Neurocognitive effects of melatonin treatment in healthy adults and individuals with Alzheimer\u2019s disease and insomnia: a systematic review and meta-analysis of randomized controlled trials","volume":"127","author":"Sumsuzzman","year":"2021","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref66","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms11082077","article-title":"Biosynthetic pathways and functions of indole-3-acetic acid in microorganisms","volume":"11","author":"Tang","year":"2023","journal-title":"Microorganisms"},{"key":"ref67","doi-asserted-by":"publisher","first-page":"100177","DOI":"10.59717\/j.xinn-life.2026.100177","article-title":"Tryptophan metabolism in inter-organ communication and its potential applications for disease prevention and control","volume":"3","author":"Tang","year":"2025","journal-title":"Innov. Life"},{"key":"ref68","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1016\/s0197-0186(01)00133-4","article-title":"Quinolinic acid stimulates synaptosomal glutamate release and inhibits glutamate uptake into astrocytes","volume":"40","author":"Tavares","year":"2002","journal-title":"Neurochem. Int."},{"key":"ref69","doi-asserted-by":"publisher","first-page":"e106700","DOI":"10.1371\/journal.pone.0106700","article-title":"The Montreal cognitive assessment (MoCA) - a sensitive screening instrument for detecting cognitive impairment in chronic hemodialysis patients","volume":"9","author":"Tiffin-Richards","year":"2014","journal-title":"PLoS One"},{"key":"ref70","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1016\/S0361-9230(02)00813-4","article-title":"Increased levels of 3-hydroxykynurenine in different brain regions of rats with chronic renal insufficiency","volume":"58","author":"Topczewska-Bruns","year":"2002","journal-title":"Brain Res. Bull."},{"key":"ref71","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1038\/s41581-020-0266-9","article-title":"Mechanisms of cognitive dysfunction in CKD","volume":"16","author":"Viggiano","year":"2020","journal-title":"Nat. Rev. Nephrol."},{"key":"ref72","doi-asserted-by":"publisher","first-page":"101037","DOI":"10.1016\/j.xkme.2025.101037","article-title":"The diagnostic performance of screening instruments for mild cognitive impairment and dementia in chronic kidney disease and kidney failure: a systematic review and meta-analysis","volume":"7","author":"Wang","year":"2025","journal-title":"Kidney Med."},{"key":"ref73","doi-asserted-by":"publisher","DOI":"10.3390\/metabo15030210","article-title":"Diverse physiological roles of kynurenine pathway metabolites: updated implications for health and disease","volume":"15","author":"Wang","year":"2025","journal-title":"Meta"},{"key":"ref74","doi-asserted-by":"publisher","first-page":"e06221","DOI":"10.1016\/j.heliyon.2021.e06221","article-title":"Effect of uremic toxins on hippocampal cell damage: analysis in vitro and in rat model of chronic kidney disease","volume":"7","author":"Watanabe","year":"2021","journal-title":"Heliyon"},{"key":"ref75","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1016\/j.chom.2014.09.001","article-title":"Discovery and characterization of gut microbiota decarboxylases that can produce the neurotransmitter tryptamine","volume":"16","author":"Williams","year":"2014","journal-title":"Cell Host Microbe"},{"key":"ref76","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines12010148","article-title":"Exploring the relationship between gut microbiome composition and blood Indole-3-acetic acid in hemodialysis patients","volume":"12","author":"Wu","year":"2024","journal-title":"Biomedicine"},{"key":"ref77","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1159\/000524475","article-title":"Chronic kidney disease and cognitive impairment: the kidney-brain Axis","volume":"8","author":"Xie","year":"2022","journal-title":"Kidney Dis."},{"key":"ref78","doi-asserted-by":"publisher","first-page":"106626","DOI":"10.1016\/j.nbd.2024.106626","article-title":"Kidney-brain axis in the pathogenesis of cognitive impairment","volume":"200","author":"Yan","year":"2024","journal-title":"Neurobiol. Dis."},{"key":"ref79","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci14111043","article-title":"AST-120 protects cognitive and emotional impairment in chronic kidney disease induced by 5\/6 nephrectomy","volume":"14","author":"Yu","year":"2024","journal-title":"Brain Sci."},{"key":"ref80","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1007\/s00726-026-03499-0","article-title":"Tryptophan metabolites clearance in hemodialyzed patients","volume":"58","author":"Zakrocka","year":"2026","journal-title":"Amino Acids"},{"key":"ref81","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1016\/j.jare.2024.08.018","article-title":"Gut microbiota-derived indole-3-propionic acid alleviates diabetic kidney disease through its mitochondrial protective effect via reducing ubiquitination mediated-degradation of SIRT1","volume":"73","author":"Zeng","year":"2025","journal-title":"J. Adv. Res."},{"key":"ref82","doi-asserted-by":"publisher","first-page":"e0304762","DOI":"10.1371\/JOURNAL.PONE.0304762","article-title":"Prevalence of cognitive impairment and its predictors among chronic kidney disease patients: a systematic review and meta-analysis","volume":"19","author":"Zhang","year":"2024","journal-title":"PLoS One"},{"key":"ref83","doi-asserted-by":"publisher","first-page":"2739","DOI":"10.1007\/s00213-020-05569-x","article-title":"Abnormalities in gut microbiota and serum metabolites in hemodialysis patients with mild cognitive decline: a single-center observational study","volume":"237","author":"Zhu","year":"2020","journal-title":"Psychopharmacology"}],"container-title":["Frontiers in Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2026.1872778\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T05:45:03Z","timestamp":1784267103000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2026.1872778\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,17]]},"references-count":82,"alternative-id":["10.3389\/fnins.2026.1872778"],"URL":"https:\/\/doi.org\/10.3389\/fnins.2026.1872778","relation":{},"ISSN":["1662-453X"],"issn-type":[{"value":"1662-453X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,17]]},"article-number":"1872778"}}