{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T18:58:09Z","timestamp":1791313089527,"version":"4.3.1"},"reference-count":100,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"crossref","award":["R01AG076537"],"award-info":[{"award-number":["R01AG076537"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01AG089380, U01AG057195, U01NS120901, U19AG032438"],"award-info":[{"award-number":["R01AG089380, U01AG057195, U01NS120901, U19AG032438"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["U19AG069701, R01AG071226, R01AG068034, R01AG081203, RF1AG057181"],"award-info":[{"award-number":["U19AG069701, R01AG071226, R01AG068034, R01AG081203, RF1AG057181"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Institute for Health Research (NIHR) Oxford Biomedical Research Centre"},{"name":"Medical Research Council","award":["MR\/V007173\/1"],"award-info":[{"award-number":["MR\/V007173\/1"]}]},{"name":"Wellcome Trust Fellowship","award":["104079\/Z\/14\/Z"],"award-info":[{"award-number":["104079\/Z\/14\/Z"]}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["JASN"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:p>\n                    Cognitive impairment involves alterations to one's cognitive status that affects everyday life. Individuals with CKD, and particularly kidney failure, experience higher rates of cognitive impairment (20%\u201370%) compared with the general population. The highest prevalence is described in kidney failure such that dialysis-dependent patients have twice the prevalence of age-matched controls. In the past 5 years, the number of investigations examining the \u201ckidney-brain axis,\u201d mechanisms of CKD-related cognitive impairment, and potential therapeutics have exponentially increased. This review article summarizes recent literature on direct and indirect effects of CKD-associated cognitive impairment with emphasis on uremic toxins; brain injury mechanisms; overlap between CKD-associated cognitive impairment, Alzheimer's disease, and other neurodegenerative diseases. Reviewed therapeutic interventions include AST-120 (indoxyl sulfate absorbent), CH-223191 (aryl hydrocarbon receptor antagonist), triarylmethane-34 (Kca3.1-specific inhibitor), anakinra (IL-1R inhibitor), marimastat, exercise, supplements, and kidney transplantation. Special focus is placed on translational studies examining uremic toxin\u2013associated pathogenic processes, including brain oxidative stress, neuroinflammation, and blood-brain barrier dysfunction through\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    models of CKD-associated brain injury. Finally, future research directions are suggested, including targeting of cellular senescence abundance with senotherapeutics and capitalizing on anti-inflammatory effects of regenerative, cell-based therapeutics (\n                    <jats:italic toggle=\"yes\">e.g<\/jats:italic>\n                    ., mesenchymal stem cells and extracellular vesicles), and use of aged murine models. Collectively, CKD-associated cognitive impairment represents a prevalent condition for which remaining knowledge gaps exist, and scientific advancements are needed to preserve cognitive function and improve the lives of individuals with CKD.\n                  <\/jats:p>","DOI":"10.1681\/asn.0000000675","type":"journal-article","created":{"date-parts":[[2025,2,26]],"date-time":"2025-02-26T12:01:19Z","timestamp":1740571279000},"page":"1208-1226","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":41,"title":["Uremic Toxins, CKD, and Cognitive Dysfunction"],"prefix":"10.1681","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3363-1549","authenticated-orcid":false,"given":"Taylor D.","family":"Andrews","sequence":"first","affiliation":[{"name":"Department of Neurosciences, Mayo Clinic Graduate School Biomedical Sciences, Mayo Clinic, Jacksonville, Florida"},{"name":"Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Jacksonville, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5133-5538","authenticated-orcid":false,"given":"Gregory S.","family":"Day","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic, Jacksonville, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7667-9748","authenticated-orcid":false,"given":"Sarosh R.","family":"Irani","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic, Jacksonville, Florida"},{"name":"Department of Neurosciences, Mayo Clinic, Jacksonville, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6751-9374","authenticated-orcid":false,"given":"Takahisa","family":"Kanekiyo","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Mayo Clinic, Jacksonville, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7485-336X","authenticated-orcid":false,"given":"LaTonya J.","family":"Hickson","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Jacksonville, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2025,2,26]]},"reference":[{"issue":"7","key":"B2-20260218","doi-asserted-by":"crossref","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."},{"issue":"9","key":"B3-20260218","doi-asserted-by":"crossref","first-page":"590","DOI":"10.3390\/toxins12090590","article-title":"Gut-derived protein-bound uremic 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