Abstract: SA-PO1123
Association Between Protein-Bound Uremic Toxins and Cognitive Function: A Cross-Sectional Study in a Community-Based Cohort
Session Information
- CKD: Progression, Drugs, Modalities, and Environmental Factors
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2301 CKD (Non-Dialysis): Epidemiology, Risk Factors, and Prevention
Authors
- Yamamoto, Suguru, Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
- Tanaka, Takahiro, Clinical and Translational Research Center, Niigata University Medical and Dental Hospital, Niigata, Japan
- Kitamura, Nobutaka, Clinical and Translational Research Center, Niigata University Medical and Dental Hospital, Niigata, Japan
- Yokoseki, Akio, Department of Inter-Organ Communication Research, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
- Wakasugi, Minako, Department of Inter-Organ Communication Research, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
- Kikuchi, Kaori, Research and Development Division, Kureha Corporation, Tokyo, Japan
- Konagai, Ayano, Research and Development Division, Kureha Corporation, Tokyo, Japan
- Goto, Shin, Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
- Narita, Ichiei, Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
Background
Cognitive dysfunction is increasingly recognized as a significant complication in chronic kidney disease (CKD). While the role of protein-bound uremic toxins (PBUTs) in this context has been hypothesized, their combined clinical impact on cognition remains insufficiently characterized.
Methods
This cross-sectional analysis included 1,217 community-dwelling individuals from the PROject in Sado for Total health (PROST). Cognitive function was assessed using the Mini-Mental State Examination (MMSE), with scores of less than 28 defined as 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 generated through principal component analysis. Multivariable logistic regression was used to assess the association between PBUT score and cognitive impairment, with comparisons to estimated glomerular filtration rate (eGFR) and serum β2-microglobulin (β2-m) levels.
Results
This analysis included 1,217 participants. Men accounted for 52.7% of the cohort, with a mean age of 65.5 ± 12.2 years. The mean eGFR was 79.6 ± 79.4 mL/min/1.73 m2, and the mean serum β2-m level was 4.0 ± 6.1 mg/L. Serum concentrations of indoxyl sulfate, p-cresyl sulfate, phenyl sulfate, indoleacetic acid, and hippuric acid were 0.358 ± 0.894 mg/dL, 0.665 ± 1.016 mg/dL, 0.251 ± 0.574 mg/dL, 0.036 ± 0.034 mg/dL, and 0.313 ± 1.130 mg/dL, respectively. The mean MMSE score was 26.7 ± 3.4. MMSE scores progressively declined with the advancement of CKD stages. Elevated PBUT scores were significantly associated with MCI (regression coefficient: 0.274, p < 0.001), and this association was stronger than those observed for either eGFR or β2-m levels.
Conclusion
PBUT burden was independently and more strongly associated with cognitive impairment than traditional kidney function markers. These findings suggest a potential pathophysiological role of PBUTs in the kidney–brain axis and underscore the need for novel strategies targeting uremic toxins to preserve cognitive health in CKD.