ArticlePsychogeriatrics : the official journal of the Japanese Psychogeriatric Society2026
The Toxic Filter: Chronic Kidney Disease Drives Neuro-Psychiatric Toxicity and Agitation in Sepsis Survivors Aged ≥ 90 Years: A Retrospective Cohort Study Using the National Database of Japan.
Article in Psychogeriatrics : the official journal of the Japanese Psychogeriatric Society, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundIn sepsis survivors aged ≥ 90 years, physiological reserve defines recovery. We previously identified liver dysfunction as protective ('liver paradox') and rehabilitation as a trigger for mental decline. Here, we hypothesised a 'metabolic dichotomy', where chronic kidney disease (CKD) damages the brain by accumulating neurotoxins, acting as a 'toxic filter'.
methodsUsing the National Database of Japan, we analysed 269 previously independent and medication-free sepsis survivors aged ≥ 90. The primary outcome was new initiation of CNS-active medications within 6 months 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.
resultsAmong 269 survivors, 49 (18.2%) had CKD. The CKD group had significantly higher antipsychotic initiation (34.7% vs. 19.1%; p = 0.022), whereas antidementia drug initiation was identical (4.1% vs. 4.1%; p = 1.00). Multivariate analysis identified CKD as an independent risk factor for overall CNS medication initiation (OR 2.85; p = 0.009). Specifically for antipsychotics, CKD's impact was more pronounced (OR 3.22; p = 0.004). Sensitivity analyses excluding renal replacement therapy yielded consistent results (OR 3.21; p = 0.006). Liver dysfunction maintained a protective trend.
conclusionUnlike the protective liver, CKD acts as a 'toxic filter', driving acute 'toxic agitation' rather than dementia in nonagenarians. This establishes the 'metabolic dichotomy'. Preserving renal filtration is synonymous with preserving sanity.
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