Elevated serum TMAO levels associate with higher risk of arteriovenous vascular access thrombosis in hemodialysis patients

Abstract Background Arteriovenous access thrombosis is a major cause of morbidity in patients receiving maintenance hemodialysis, and conventional clinical and anatomical risk factors do not fully explain its occurrence. Trimethylamine-N-oxide (TMAO), a gut microbiota–derived metabolite that accumulates in kidney failure and exhibits prothrombotic properties, has been linked to cardiovascular events in dialysis populations. Its relevance to dialysis arteriovenous access outcomes, however, remains unclear. Methods We conducted a multicenter prospective cohort study including 375 adult patients undergoing maintenance hemodialysis at 12 centers in Taiwan. Baseline serum TMAO concentrations were measured using liquid chromatography–tandem mass spectrometry and analyzed as tertiles and as a log-transformed continuous variable. Participants were followed for a median of 24 months. The primary outcome was time to first arteriovenous access thrombosis. Associations were evaluated using Cox proportional hazards models with multivariable adjustment and restricted cubic spline analyses. Results During a median follow-up of 24 months, 88 patients (23%) experienced arteriovenous access thrombosis. Thrombosis incidence increased stepwise across TMAO tertiles (13%, 23%, and 34%; P 0.001). In unadjusted analysis, patients in the highest TMAO tertile had a higher risk of thrombosis compared with the lowest tertile (unadjusted hazard ratio 3.10; 95% confidence interval 1.75–5.51). This association remained significant after multivariable adjustment (adjusted hazard ratio 2.87; 95% confidence interval 1.60–5.17). Results were consistent in competing-risk analyses treating death as a competing event. Addition of TMAO to a baseline clinical model yielded modest improvement in discrimination (ΔC = 0.011, 95% CI − 0.047 to 0.070; P = 0.051). Conclusion Higher serum TMAO levels were independently associated with an increased risk of arteriovenous access thrombosis in patients undergoing hemodialysis. These findings suggest that TMAO reflects a systemic prothrombotic milieu relevant to dialysis arteriovenous access and support further studies to determine whether TMAO represents a modifiable pathway or a biomarker of uremic thrombotic susceptibility.