Association of tryptophan metabolites with cognitive impairment in chronic kidney disease
Year: 2026
Type: article
Study design: Observational Study
Abstract: Background: Chronic kidney disease (CKD) leads to the accumulation of uremic toxins (UTs), including tryptophan-derived metabolites such as kynurenine (KYN), indoxyl sulfate (IS), and indole-3-acetic acid (IAA). IS has been identified as a potential contributor to cognitive impairment (CI), whereas less is known about the other tryptophan metabolites. We aimed to evaluate the association between these toxins related to tryptophan metabolism and CI in patients with CKD. Methods: Three thousand thirty-three patients with CKD stages 2-5 enrolled in CKD-Renal Epidemiology and Information Network (CKD-REIN) cohort. Patients with both UT measurement and cognitive function screening [with mini-mental state examination (MMSE)] were included. CI was defined as an MMSE score ≤ 26/30. Logistic regression was used to assess the association between the studied UTs and MMSE. Results: ], 858 patients (35.9%) had an MMSE score ≤26/30. After adjustment for sociodemographic factors, cardiovascular risk factors, cerebrovascular disease, current depression, eGFR, urinary albumin-to-creatinine ratio, and UTs known to be associated with CI, no significant association was found between KYN or IAA and MMSE ≤26/30, whereas IS was significantly associated [Odds Ratio (OR), 95% confidence interval: 1.11 (1.00-1.21)]. Conclusion: Among tryptophan-derived metabolites studied, IS was associated with CI in patients with CKD, in contrast to KYN and IAA. Despite sharing a common origin, the UTs studied follow distinct metabolic pathways with different effects, highlighting the need for further investigation of the tryptophan pathway on CI in CKD.
Source: Clinical Kidney Journal
DOI: 10.1093/ckj/sfag199
Authors: Gaye Hafez, Ziad A Massy, Jean-Claude Alvarez, Marion Pépin, Solène M Laville, Natalia Alencar de Pinho, Islam Amine Larabi, Sophie Liabeuf, Hélène Levassort, CKD-REIN Study Collaborators, Natalia Alencar de Pinho, Dorothée Cannet, Christian Combe, Denis Fouque, Luc Frimat, Aghilés Hamroun, Yves-Edouard Herpe, Christian Jacquelinet, Maurice Laville, Sophie Liabeuf, Ziad A Massy, Pascal Morel, Roberto Pecoits-Filho, Joost Schanstra, Bénédicte Stengel, Céline Lange, Oriane Lambert, Marie Metzger, Emilie Moutard
Institutions: Inserm, Université de Versailles Saint-Quentin-en-Yvelines, Université Paris-Saclay, Centre de recherche en Epidémiologie et Santé des Populations, Altınbaş University, Hôpital Ambroise-Paré, Assistance Publique – Hôpitaux de Paris, Hôpital Raymond-Poincaré, Centre Hospitalier Universitaire Amiens-Picardie, Mécanismes physiopathologiques et conséquences des calcifications cardiovasculaires, Université de Picardie Jules Verne
Language: English
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,335
Award: G5188869101
OpenAlex ID: W7165042978
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