Acute Kidney Injury, Systemic Inflammation, and Long-Term Cognitive Function

Key Points This study highlights that AKI is associated with long-term cognitive decline. Soluble TNF receptor 1 concentrations seem to mediate a significant proportion of the risk of long-term cognitive impairment after AKI. Background Cognitive dysfunction is a well-known complication of CKD, but it is less known whether cognitive decline occurs in survivors after AKI. We hypothesized that an episode of AKI is associated with poorer cognitive function, mediated, at least in part, by persistent systemic inflammation. Methods Assessment, Serial Evaluation and Subsequent Sequelae of AKI enrolled patients surviving 3 months after hospitalization with and without AKI matched on the basis of demographics, comorbidities, and baseline kidney function. A subset underwent cognitive testing using the modified mini-mental status examination (3MS) at 3, 12, and 36 months. We examined the association of AKI with 3MS scores using mixed linear models and assessed the proportion of risk mediated by systemic inflammatory biomarkers. Results Among 1538 participants in Assessment, Serial Evaluation and Subsequent Sequelae of AKI, 1420 (92%) completed the 3MS assessment at 3 months and had a corresponding matched participant. Participants with AKI had lower 3MS scores at 3 years (difference −1.1 [95% confidence interval, −2.0 to −0.3] P = 0.009) compared with participants without AKI. A higher proportion of participants with AKI had a clinically meaningful (≥5 point) reduction in 3MS scores at 3 years compared with participants without AKI (14% versus 10%, P = 0.04). In mediation analyses, plasma-soluble TNF receptor-1 at 3 months after AKI mediated 35% ( P = 0.02) of the AKI-related risk for 3MS scores at 3 years. Conclusions AKI was associated with lower 3MS scores, and Soluble TNF receptor 1 concentrations seemed to mediate a significant proportion of the risk of long-term cognitive impairment. Further work is needed to determine whether AKI is causal or a marker for cognitive impairment.