Trimethylamine N-Oxide and Cardiovascular Outcomes in Patients with ESKD Receiving Maintenance Hemodialysis

Background and objectives Trimethylamine N-oxide (TMAO), a compound derived from byproducts of intestinal bacteria, has been shown to accelerate atherosclerosis in rodents. To date, there are conflicting data regarding the association of serum TMAO with cardiovascular outcomes in patients with ESKD, a population exhibiting both high serum TMAO and excessive atherosclerosis.

Design, setting, participants, & measurements We measured baseline serum TMAO concentrations in a subset of participants (n=1243) from the Evaluation of Cinacalcet Hydrochloride Therapy to Lower Cardiovascular Events (EVOLVE) trial and conducted post hoc analyses evaluating the association between baseline serum TMAO and cardiovascular outcomes.

Results We observed a wide distribution of serum TMAO in our cohort, with approximately 80% of participants exhibiting TMAO concentrations ≥56 µM and a maximum TMAO concentration of 1103.1 µM. We found no association between TMAO and our primary outcome, a composite of cardiovascular mortality, myocardial infarction, peripheral vascular event, stroke, and hospitalization for unstable angina. Moreover, in unadjusted and adjusted analyses, we observed no relation between TMAO and all-cause mortality, the independent components of our composite outcome, or the original EVOLVE primary outcome. Although we did observe higher TMAO concentrations in white participants, further subgroup analyses did not confirm the previously identified interaction between TMAO and race observed in a prior study in patients receiving dialysis.

Conclusions We found no evidence linking TMAO to adverse clinical outcomes in patients receiving maintenance hemodialysis with moderate to severe secondary hyperparathyroidism.