Protein-Bound Uremic Toxins and Cognitive Function: A Cross-Sectional Study in a Community-Based Cohort

Cognitive dysfunction is increasingly recognized as a significant complication of chronic kidney disease (CKD), but the clinical relevance of protein-bound uremic toxins (PBUTs) to cognition remains insufficiently characterized. This cross-sectional analysis included 1217 community-dwelling individuals. Cognitive function was assessed using the Mini-Mental State Examination (MMSE), with scores < 28 indicating possible mild cognitive impairment (MCI). Serum concentrations of five PBUTs-indoxyl sulfate, p-cresyl sulfate, phenyl sulfate, indoleacetic acid, and hippuric acid-were measured, and a composite PBUT score was derived using principal component analysis. Multivariable logistic regression was used to examine the associations of MCI with the PBUT score and with each PBUT. Serum PBUT concentrations increased with advancing CKD stage. The mean MMSE score was 26.7 ± 3.4, and scores progressively declined with advancing CKD stage. A higher PBUT score was independently associated with MCI (coefficient, 0.290 ± 0.077; odds ratio, 1.337; 95% confidence interval, 1.151-1.554; p < 0.001). In conclusion, a greater PBUT burden was independently associated with cognitive impairment. These findings identify PBUT burden as a potential correlate of cognitive impairment in CKD. Prospective studies are needed to clarify its temporal relationship with cognitive decline and to assess whether it provides predictive value beyond established measures of kidney function.