Associations Between Renal Function, Uremic Toxins, and Cognitive Performance in Patients with Chronic Kidney...

Patients with chronic kidney disease (CKD) often experience cognitive decline. However, the associations between renal dysfunction, uremic toxins, and cerebrovascular changes remain unclear.

This study investigated the associations between renal function, uremic toxins, cerebrovascular imaging markers, and cognitive performance in patients with CKD plus early cognitive decline through integrated biochemical, neuropsychological, and neuroimaging assessments.

An observational pilot study.

Outpatient clinic of the physical medicine and rehabilitation department at a tertiary hospital.

Adult patients with stage 3-5 CKD who exhibited early cognitive decline and could complete CANTAB-based cognitive assessments.

This study included 12 patients with stage 3-5 CKD who were not undergoing hemodialysis and had early cognitive decline (Clinical Dementia Rating score: 0.5 or 1.0). Cognitive performance was assessed using the CANTAB. Serum levels of total indoxyl sulfate (IS) and total p-cresyl sulfate (pCS) were measured. Brain magnetic resonance imaging was performed to evaluate qualitative imaging markers potentially associated with cognitive impairment, such as arterial stenosis of the circle of Willis. Pearson correlations between the aforementioned biomarkers were explored.

Both IS and pCS levels were negatively correlated with estimated glomerular filtration rate (IS: r = -0.301, p = 0.469; pCS: r = -0.461, p = 0.250). A higher estimated glomerular filtration rate was correlated with better spatial working memory strategy performance (r = 0.695, p = 0.012). However, no clear correlation was observed between cognitive performance and arterial stenosis severity.

This pilot study suggests that renal function is associated with selected cognitive domains in patients with CKD. The overall burden of qualitative MRI lesions was low in this cohort, although structural brain abnormalities were still observed. Integration of biochemical, neuropsychological, and brain imaging biomarkers may provide a comprehensive evaluation of cognitive function in these patients.

Integrating multidomain cognitive assessments with uremic toxin profiling and noninvasive brain imaging may facilitate early identification of cognitive deficits in patients with CKD, thereby supporting individualized cognitive evaluation in rehabilitation practice.Trial Registration: NCT07272733.