Protein-Bound Uremic Toxins and Cognitive Function: A Cross-Sectional Study in a Community-Based Cohort.
5 affiliations
- 1Division of Clinical Nephrology and Rheumatology, Kidney Research Center, Graduate School of Medicine, Dentistry and Health Sciences, Niigata University, Niigata 951-8510, Japan.
- 2Clinical and Translational Research Center, Niigata University Medical and Dental Hospital, Niigata 951-8510, Japan.
- 3Department of Inter-Organ Communication Research, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, Japan.
- 4Sado General Hospital, Niigata 952-1209, Japan.
- 5Research and Development Division, Kureha Corporation, Tokyo 103-8552, Japan.
Abstract
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.
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BibTeX
@article{yamamoto2026proteinbound,
title = {{Protein-Bound Uremic Toxins and Cognitive Function: A Cross-Sectional Study in a Community-Based Cohort.}},
author = {Suguru Yamamoto and Takahiro Tanaka and Nobutaka Kitamura and Miho Kawachi and Akio Yokoseki and Minako Wakasugi and Osamu Onodera and Naoto Endo and Masakazu Wada and Kenji Sato and Kaori Kikuchi and Ayano Konagai and Shin Goto and Ichiei Narita},
journal = {Toxins},
year = {2026},
month = sep,
doi = {10.3390/toxins18100422},
url = {https://europepmc.org/article/MED/42931513},
note = {CC BY},
}
RIS
TY - JOUR
TI - Protein-Bound Uremic Toxins and Cognitive Function: A Cross-Sectional Study in a Community-Based Cohort.
AU - Suguru Yamamoto
AU - Takahiro Tanaka
AU - Nobutaka Kitamura
AU - Miho Kawachi
AU - Akio Yokoseki
AU - Minako Wakasugi
AU - Osamu Onodera
AU - Naoto Endo
AU - Masakazu Wada
AU - Kenji Sato
AU - Kaori Kikuchi
AU - Ayano Konagai
AU - Shin Goto
AU - Ichiei Narita
PY - 2026
DA - 2026/09/30
JO - Toxins
DO - 10.3390/toxins18100422
UR - https://europepmc.org/article/MED/42931513
AB - 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.
SN - 2072-6651
ER -