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

Psychogeriatrics. 2026 Jul;26(4):e70191. doi: 10.1111/psyg.70191.

ABSTRACT

BACKGROUND: In 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'.

METHODS: Using 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.

RESULTS: Among 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.

CONCLUSION: Unlike 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.

PMID:42411180 | DOI:10.1111/psyg.70191