{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T02:04:13Z","timestamp":1784081053962,"version":"3.55.0"},"reference-count":17,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP21K09088"],"award-info":[{"award-number":["JP21K09088"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Psychogeriatrics"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>In sepsis survivors aged \u2265\u200990\u2009years, physiological reserve defines recovery. We previously identified liver dysfunction as protective (\u2018liver paradox\u2019) and rehabilitation as a trigger for mental decline. Here, we hypothesised a \u2018metabolic dichotomy\u2019, where chronic kidney disease (CKD) damages the brain by accumulating neurotoxins, acting as a \u2018toxic filter\u2019.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using the National Database of Japan, we analysed 269 previously independent and medication\u2010free sepsis survivors aged \u2265\u200990. The primary outcome was new initiation of CNS\u2010active medications within 6\u2009months after ICU admission. A secondary analysis compared initiation of antipsychotics (agitation\/delirium) versus antidementia drugs. We performed multivariate logistic regression adjusting for confounders including rehabilitation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 269 survivors, 49 (18.2%) had CKD. The CKD group had significantly higher antipsychotic initiation (34.7% vs. 19.1%;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.022), whereas antidementia drug initiation was identical (4.1% vs. 4.1%;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20091.00). Multivariate analysis identified CKD as an independent risk factor for overall CNS medication initiation (OR 2.85;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.009). Specifically for antipsychotics, CKD's impact was more pronounced (OR 3.22;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.004). Sensitivity analyses excluding renal replacement therapy yielded consistent results (OR 3.21;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.006). Liver dysfunction maintained a protective trend.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Unlike the protective liver, CKD acts as a \u2018toxic filter\u2019, driving acute \u2018toxic agitation\u2019 rather than dementia in nonagenarians. This establishes the \u2018metabolic dichotomy\u2019. Preserving renal filtration is synonymous with preserving sanity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/psyg.70191","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T07:52:20Z","timestamp":1783410740000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Toxic Filter: Chronic Kidney Disease Drives Neuro\u2010Psychiatric Toxicity and Agitation in Sepsis Survivors Aged \u2265\u200990\u2009Years: A Retrospective Cohort Study Using the National Database of Japan"],"prefix":"10.1111","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9679-8699","authenticated-orcid":false,"given":"Yuichiro","family":"Shimoyama","sequence":"first","affiliation":[{"name":"Department of Anesthesiology Osaka Medical and Pharmaceutical University, Intensive Care Unit, Osaka Medical and Pharmaceutical University Hospital  Takatsuki Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriko","family":"Kadono","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Osaka Medical and Pharmaceutical University, Intensive Care Unit, Osaka Medical and Pharmaceutical University Hospital  Takatsuki Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Umegaki","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Osaka Medical and Pharmaceutical University, Intensive Care Unit, Osaka Medical and Pharmaceutical University Hospital  Takatsuki Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,7]]},"reference":[{"key":"e_1_2_11_2_1","article-title":"Iatrogenic and Metabolic Factors Associated With New\u2010Onset Home Medical Care in \u2018Super\u2010Normal\u2019 Sepsis Patients Aged \u2265\u200990: A Nationwide Study","author":"Shimoyama Y.","journal-title":"Geriatrics & Gerontology International"},{"issue":"9791","key":"e_1_2_11_3_1","first-page":"564","article-title":"The 100\u2010Year\u2010Old Population in Japan","volume":"378","author":"Christensen K.","year":"2011","journal-title":"Lancet"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-019-05853-1"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0b013e318232da75"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2010.1553"},{"key":"e_1_2_11_7_1","article-title":"The Scalpel Cuts Deeper Than the Ventilator: General Anesthesia Drives a Phenotypic Shift Toward Sleep\u2010Sensory Dysregulation","author":"Shimoyama Y.","journal-title":"Journal of Intensive Care"},{"key":"e_1_2_11_8_1","unstructured":"Y.Shimoyama N.Kadono andO.Umegaki \u201cThe Rehabilitation Paradox: Active Physical Recovery Drives Neuro\u2010Psychiatric Exhaustion in Super\u2010Elderly Sepsis Survivors \u201dunder review."},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2003.00924.x"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2012050536"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0031-1277984"},{"issue":"10","key":"e_1_2_11_12_1","first-page":"511","article-title":"Overview of the NDB (National Database of Health Insurance Claims and Specific Health Checkups) of Japan","volume":"26","author":"Ikeda S.","year":"2016","journal-title":"Journal of Epidemiology"},{"issue":"10","key":"e_1_2_11_13_1","first-page":"604","article-title":"Validity of Diagnoses, Procedures, and Laboratory Data in Japanese Administrative Data","volume":"25","author":"Yamana H.","year":"2015","journal-title":"Journal of Epidemiology"},{"issue":"1","key":"e_1_2_11_14_1","first-page":"1","article-title":"Uremic Toxicity of Indoxyl Sulfate","volume":"72","author":"Niwa T.","year":"2010","journal-title":"Nagoya Journal of Medical Science"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1990.2"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(95)91209-6"},{"issue":"10","key":"e_1_2_11_17_1","first-page":"1903","article-title":"Guanidino Compounds in Serum and Cerebrospinal Fluid of Non\u2010Dialyzed Patients With Renal Insufficiency","volume":"42","author":"De Deyn P. 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