Article Dans Une Revue Nephrology Dialysis Transplantation Année : 2025

[Poster]#794 Phenylacetylglutamine's role in the link between uremic toxins and cognition in chronic kidney disease: a CKD-REIN cohort study

Résumé

Background and Aims Chronic kidney disease (CKD) leads to the accumulation of uremic toxins (UTs). Many studies have suggested that UTs are associated with cognitive impairment (CI) in CKD patients. It was recently reported that phenylacetylglutamine (PAG) contributes to the association between CKD and CI. To the best of our knowledge, this association has not been investigated in non-dialysis-dependent adults with CKD. Method The CKD-REIN cohort study included 3033 patients with CKD stages 2 to 5; the present cross-sectional analysis included those with a serum PAG measurement and a Mini-Mental State Examination (MMSE) score within 3 months of each other. CI was defined as an MMSE score ≤26/30. Logistic regression models were used to assess the association between the serum PAG levels and CI. Results Of the 2590 patients included (mean (standard deviation (SD)) age: 67 (13); males: 66%; mean (SD) estimated glomerular filtration rate (eGFR): 34 (13) mL/min/1.73 m2; median [interquartile range] serum PAG level: 2.1 [1.2–3.6] mg/L), 908 (35%) presented an MMSE score ≤26/30. After adjustment for sociodemographic factors (age, sex, and educational level), cardiovascular risk factors, cerebrovascular disease, eGFR, urinary albumin to creatinine ratio and other UTs known to be associated with CI risk (indoxyl sulfate, p-cresyl sulfate and trimethylamine-N-oxide), a two-fold increase in the serum PAG levels was associated with CI (odds ratio [95% confidence interval]: 1.15 [1.02, 1.29]). Conclusion The results of this large study show that elevated serum PAG levels are associated with CI in non-dialysis-dependent adults with CKD and highlight a new physiological pathway underlying this association between UTs and CI. Further studies are needed to confirm the causal nature of this association and to explore strategies for reducing serum PAG levels and thus protecting cognitive function.

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Dates et versions

hal-05349394 , version 1 (05-11-2025)

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Helene Levassort, Julie Boucquemont, Sophie Liabeuf, Solene Laville, Luc Frimat, et al.. [Poster]#794 Phenylacetylglutamine's role in the link between uremic toxins and cognition in chronic kidney disease: a CKD-REIN cohort study. Nephrology Dialysis Transplantation, 2025, 40 (Supplement_3), pp.i961-i962. ⟨10.1093/ndt/gfaf116.0495⟩. ⟨hal-05349394⟩
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