Abstract: FR-PO0526
Gut Microbiota-Derived Metabolites and Peripheral Artery Disease in Patients on Hemodialysis: Insights into the Gut-Vascular Axis
Session Information
- CKM: Clinical - Trials, Epidemiology, and Biomarkers
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Cardiovascular-Kidney-Metabolic Health
- 602 Cardiovascular-Kidney-Metabolic Health: Clinical
Authors
- Lin, Ting-yun, Taipei Tzu Chi Hospital, Taipei City, Taiwan
- Hung, Szu-Chun, Taipei Tzu Chi Hospital, Taipei City, Taiwan
Background
Peripheral artery disease (PAD) is highly prevalent in patients receiving maintenance hemodialysis and contributes significantly to morbidity and mortality. While traditional risk factors such as age and diabetes mellitus (DM) are established predictors, the role of gut microbiota-derived uremic toxins as functional intermediaries in the pathogenesis of PAD remains poorly defined.
Methods
In a cross-sectional cohort of 278 hemodialysis patients, PAD was defined as an ankle-brachial index (ABI) < 0.9. We quantified 24 gut-derived metabolites using LC-MS/MS. To enhance reproducibility and account for the discovery-based nature of the metabolomic panel, we adopted a stringent significance threshold of P < 0.005 for biomarker identification. Incremental diagnostic value was assessed by adding metabolites to a baseline clinical model including age, DM, cardiovascular disease (CVD), systolic blood pressure (SBP), total cholesterol, and C-reactive protein (CRP). Mediation was examined via bootstrap analysis (1,000 iterations).
Results
Patients with PAD exhibited significantly higher median levels of phenylalanine-derived PAGln (118.25 vs. 91.47 µM; P = 0.0049) and tyrosine-derived p-Cresol glucuronide (10.32 vs. 6.10 µM; P = 0.0036) compared to those with normal ABI. A traditional risk factor model (Age, DM, CVD, SBP, total cholesterol, and CRP) yielded an AUC of 0.763, which increased to 0.771 upon the addition of both metabolites (P = 0.318 for improvement). While p-Cresol glucuronide shared significant variance with DM, bootstrap analysis confirmed it as a significant pathophysiological mediator of the association between DM and PAD risk (mean indirect effect = 0.1495; 95% CI: 0.0012–0.3448), accounting for 11.7% of the total effect.
Conclusion
Gut-derived uremic toxins, specifically p-Cresol glucuronide, are robustly associated with PAD in HD patients. Although p-Cresol glucuronide shares variance with traditional clinical predictors, its role as a significant mediator underscores the gut-vascular axis as a distinct pathophysiological dimension of diabetic vascular complications. These findings suggest that the gut microbiome represents a modifiable target to alleviate the cardiovascular-kidney-metabolic burden in the dialysis population.