TOPLINE:

In patients with chronic kidney disease (CKD), higher serum levels of the uraemic toxin indoxyl sulphate were independently associated with a greater likelihood of cognitive impairment, whereas those of kynurenine and indole-3-acetic acid were not.

METHODOLOGY:

• Researchers conducted a cross-sectional analysis of data from a French cohort between 2013 and 2016 to assess the association between tryptophan-derived uraemic toxins — indoxyl sulphate, kynurenine, and indole-3-acetic acid — and cognitive impairment in CKD.
• They analysed data of 2389 adult patients with CKD stages 2-5 (mean age, 66.5 years; 66% men; mean estimated glomerular filtration rate, 34.8 mL/min/1.73 m²) who had no prior dialysis or kidney transplantation and had both uraemic toxin measurements and cognitive screening results available.
• Cognitive impairment was assessed using the 30-item Mini-Mental State Examination (MMSE) questionnaire, with impairment defined as an MMSE score of 26 or lower.
• Free serum levels of uraemic toxins were measured using validated liquid chromatography-tandem mass spectrometry.

TAKEAWAY:

• Overall, 858 (35.9%) patients with CKD had cognitive impairment.
• Higher serum indoxyl sulphate levels were independently associated with a greater likelihood of cognitive impairment (adjusted odds ratio [aOR], 1.11; P = .03).
• Sensitivity analysis found that compared with the lowest indoxyl sulphate group, the highest group was associated with a more than 40% higher likelihood of an MMSE score ≤ 26/30 (aOR, 1.43; P = .02).
• No significant association was found between kynurenine or indole-3-acetic acid levels and cognitive impairment.

IN PRACTICE:

"Among tryptophan circulating derivatives, higher IS [indoxyl sulphate] levels are independently associated with CI [cognitive impairment] in patients with CKD, in contrast to KYN [kynurenine] and IAA [indole-3-acetic acid]," the authors wrote.

"Determining biological risk factors for neurological complications will help optimize therapeutic management and develop new treatment strategies," they added.

SOURCE:

This study was led by Gaye Hafez, Université Paris-Saclay, Centre de Recherche en Epidémiologie et Santé des Populations, Villejuif, Paris, France. It was published online on June 17, 2026, in Clinical Kidney Journal.

LIMITATIONS:

The study design prevented the establishment of a causal relationship. The use of the MMSE questionnaire did not effectively screen for executive dysfunction, which may have introduced an assessment bias. Additionally, the study did not account for effects of dietary factors or nutrition.

DISCLOSURES:

The cohort study received financial support from the "Cohortes-Investissements d'Avenir" programme, the French Ministry of Higher Education and Research, and the national 2010 Hospital Clinical Research Programme, with additional support received through a public-private partnership with various pharmaceutical companies. Some authors reported receiving grants or financial support, including funding related to the cohort study, or serving on advisory boards for various pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.