Acute Kidney Injury and Risk of Adverse Neurocognitive Outcomes: A Systematic Review and Meta-Analysis.

Overview

1. Wolfson Centre for the Prevention of Stroke and Dementia, Nuffield Department of Clinical Neurosciences, University of Oxford, United Kingdom
2. Division of Critical Care, Department of Anesthesiology, Brigham and Women's Hospital, Boston, MA
3. Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston; and
4. Nuffield Department of Clinical Neurosciences, University of Oxford, United Kingdom

Abstract

Background and Objectives: Chronic kidney disease is a recognized risk factor for adverse neurocognitive outcomes, but the effect of acute kidney injury (AKI) on brain health remains less well defined. We conducted a systematic review and meta-analysis to evaluate associations between AKI and subsequent risk of stroke, delirium, and dementia.

Methods: Eligible studies were identified by searching Ovid MEDLINE and Embase from inception (Ovid: January 1946; Embase: January 1970) until April 2025. Studies were included if they reported quantitative estimates with measures of precision for the association between AKI and delirium, stroke, or dementia in adult populations. Two reviewers independently screened and extracted data, and study quality was assessed using standardized criteria. Study characteristics, participant demographics, and adjusted effect estimates (hazard ratios [HRs] or odds ratios [ORs]) with 95% CIs were extracted. Pooled HRs and ORs with 95% CIs were calculated using random-effects models. Heterogeneity was evaluated with the χ2 test and I2 statistic, and sources of heterogeneity were explored through prespecified subgroup analyses and meta-regression.

Results: We identified 49 studies comprising 11,253,825 participants with 1,279,145 events. Individuals with AKI were at increased risk of stroke (pooled adjusted HR 1.35, 95% CI 1.20–1.52), delirium (pooled adjusted OR 1.76; 1.42–2.17), and dementia (pooled adjusted HR 1.64, 1.41–1.89). A gradient of risk across increasing AKI stages was demonstrated for stroke (stage 1: HR 1.11; 1.00–1.23; combined stages 2 and 3: HR 1.57; 1.35–1.81). AKI was also associated with higher in-hospital and 90-day mortality poststroke (pooled HR 2.13, 1.56–2.90, and 4.81, 2.55–9.08, respectively) and with 90-day disability (pooled adjusted OR 1.47, 1.22–1.76). Associations between AKI and all outcomes were directionally consistent across sensitivity analyses and pooled propensity score–matched studies.

Discussion: In this systematic review and meta-analysis, AKI was consistently associated with increased short-term and long-term neurocognitive risk, including stroke, delirium, and dementia. These findings suggest that AKI may identify individuals vulnerable to both acute and chronic brain injury. Further studies are needed to clarify mechanisms linking AKI to brain injury and to identify strategies to mitigate neurocognitive risk in this high-risk population.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data Availability

Data were derived from previously published studies identified through systematic database searches. The data extracted and code used for analyses are available from the corresponding author upon reasonable request.

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Version 2, 28 September 2026

• Publisher: n/a → Lippincott Williams & Wilkins

Version 1, 28 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 3 authors, 6 MeSH terms, 2 funders, 28 references.

Cite

This paper

Kelly, D. M., Kelleher, E. M., & Rothwell, P. M. (2026). Acute Kidney Injury and Risk of Adverse Neurocognitive Outcomes: A Systematic Review and Meta-Analysis. Neurology, 106(11), e218031. https://doi.org/10.1212/wnl.0000000000218031

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