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

Clinical Snapshot

Key Findings

• P Value: Not explicitly reported but confidence intervals exclude null

• Effect Size: Stroke HR 1.35, Delirium OR 1.76, Dementia HR 1.64

• Primary Outcome: Increased risk of stroke, delirium, and dementia following AKI

• Nnt Or Sensitivity: Dose-response gradient: AKI stage 1 stroke HR 1.11 (1.00-1.23), stages 2-3 HR 1.57 (1.35-1.81)

• Confidence Interval: Stroke (1.20-1.52), Delirium (1.42-2.17), Dementia (1.41-1.89)

Clinical Application

Risk stratification feasible using existing AKI staging criteria and clinical monitoring systems Relevant to Australian practice with implications for ACSQHC AKI recognition programs and ANZICS-CORE registry data collection Adult patients experiencing AKI in hospital or community settings

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.

References

1. 1.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. https://doi.org/10.1212/WNL.0000000000218031