Acute Kidney Injury Is Associated With Subtle but Quantifiable Neurocognitive Impairments

Jessica A. Vanderlinden; Joanna S. Semrau; Samuel A. Silver; Rachel M. Holden; Stephen H. Scott; J. Gordon Boyd


Nephrol Dial Transplant. 2022;37(2):285-297. 

In This Article


Although neurocognitive impairment is highly prevalent in patients with CKD,[26] the impacts of AKI on the brain are largely unknown. This is the first prospective study to quantify neurocognitive functioning in patients who experience a single episode of AKI. We demonstrated that robotic technology was able to quantify subtle impairments in patients who experience an episode of AKI, which were not detected by a traditional assessment (RBANS). Particularly, impairment was seen in the domains of attention, visuomotor and executive function when compared with healthy controls. When compared with a control group matched for cardiovascular risk factors (but with no history of kidney disease), AKI patients on average performed worse in the domains of attention, visuomotor and executive function. Furthermore, performance was generally not affected by whether or not renal recovery had occurred or if dialysis was required, although the numbers for subgroup analyses were low, thus limiting our ability to draw causal inferences about the association between AKI and neurocognitive performance.

For the majority of our cohort of patients with AKI, no impairment was detected using a common neuropsychological screening battery for neurocognitive impairment. Robotic technology, however, was able to quantify robust and often profound impairments in several neurocognitive domains (5–52% impairment, Kinarm task dependent). This is similar to what we have demonstrated in patients with CKD,[11] although the impairments in patients with AKI were not as severe. These impairments were detected in ~25% of the AKI cohort who were impaired at both initial and follow-up assessments, when compared with healthy controls. Subtle impairments in attention, executive function and visuomotor abilities may lead patients to have a lower quality of life, and experience difficulties in everyday tasks. Furthermore, depression scores will need to be collected as it is known that depression occurs frequently after critical illness,[27] and affects neurocognitive performance in patients with CKD.[28,29] Presently, however, follow-up data regarding maintenance and quality of life for patients with AKI post-hospitalization are limited,[30] and will need to be addressed in future research.

Interestingly, patients who experience an episode of AKI on average performed worse when compared with an active control group on tasks that measured attention, visuomotor and executive function. The mechanisms underlying this impairment are not clear; however, an animal model of AKI demonstrated that mice developed acute locomotor dysfunction, presumably related to high levels of circulating inflammatory cytokines in addition to astrocyte and microglial activation.[31] Future studies should aim to characterize the relationship between neurocognitive, kidney recovery, systemic inflammatory markers and imaging evidence of structural brain pathology. Additionally, many of the impairments captured with Kinarm were only detected at the first assessment and not at follow-up. The mechanism(s) of this improved performance over time is unclear, but it is unlikely due to learning alone, as both the RBANS and Kinarm are relatively robust to learning effects.[23,24]

This is the first prospective observational study to demonstrate quantitative deficits in neurocognitive function in individuals after a single episode of AKI. However, our study has several limitations. First, the follow-up rate was lower than anticipated. The main reason for this was the COVID-19 pandemic, as many of the patients were recruited in the months immediately preceding the pandemic. Our hospital transitioned primarily to virtual visits, which precluded neurocognitive follow-up for a large proportion of our cohort. Second, our single-center design limits external generalizability, as our study only included Caucasian individuals, which reflects our local demographics (only 5% of our region identified as a visible minority).[32] This, however, is not reflective of the general AKI population.[1] Third, we compared Kinarm with RBANS, which although comprehensive is not a substitute for a full neuropsychological battery administered by a trained neuropsychologist. Finally, to discern whether AKI is the sole cause of the neurocognitive impairment, a larger cohort is needed to untangle the independent effects of AKI from other important covariates such as: underlying precipitant, severity of disease and comorbid illnesses.

Despite these limitations, this study has the following strengths. Importantly, this study has a well-defined AKI survivor population that was collected from a specialized AKI referral clinic within a year of the event. Second, we used novel robotic technology that provides robust, objective and quantifiable data on neurocognitive performance, allowing for detection of subtle impairments. Third, we used both healthy control data that were matched for age and sex, along with a matched active control group, to quantify the neurocognitive impairment experienced in patients with AKI. Lastly, we are the first investigators to longitudinally investigate the neurocognitive performance after an episode of AKI, demonstrating that impairments are common (and can be severe), which emphasizes the need to perform neurocognitive assessments (or at least screening) early in the care of these patients. This study will help guide future research regarding the quantification of neurocognitive impairments experienced by those that survive an episode of AKI.

In summary, this is the first study to quantify neurocognitive impairment in individuals after a recent episode of AKI. By using robotic technology, we were able to quantify subtle impairments in attention, executive function and visuomotor function that were not detected by a routine clinical assessment. Patients with AKI performed worse than individuals matched for age, sex and handedness, as well patients matched for cardiovascular risk factors. Further studies are needed to discern the true extent of this impairment and how it affects the patients' quality of life, including implications for how the cognitive health of survivors of should be assessed and managed.