Elevated Serum Trimethylamine N-Oxide Levels Are Associated with Mortality in Male Patients on Peritoneal Dialysis

Blood Purif. 2021;50(6):837-847. doi: 10.1159/000512962. Epub 2021 Feb 17.

Abstract

Background: Elevated levels of serum trimethylamine N-oxide (TMAO) have been previously linked to adverse cardiovascular (CV) and all-cause mortality in hemodialysis patients. However, the clinical significance of serum TMAO levels in patients treated with peritoneal dialysis (PD) is unclear.

Methods: A total of 1,032 PD patients with stored serum samples at baseline were enrolled in this prospective study. Serum concentrations of TMAO were quantified by ultra-performance liquid chromatography-tandem mass spectrometry. Cox proportional hazards and competing-risk regression models were performed to examine the association of TMAO levels with all-cause and CV mortality.

Results: The median level of serum TMAO in our study population was 34.5 (interquartile range (IQR), 19.8-61.0) μM. During a median follow-up of 63.7 months (IQR, 43.9-87.2), 245 (24%) patients died, with 129 (53%) deaths resulting from CV disease. In the entire cohort, we observed an association between elevated serum TMAO levels and all-cause mortality (adjusted subdistributional hazard ratio [SHR], 1.22; 95% confidence interval [95% CI], 1.01-1.48; p = 0.039) but not CV mortality. Further analysis revealed such association differed by sex; the elevation of serum TMAO levels was independently associated with increased risk of both all-cause (SHR, 1.37; 95% CI, 1.07-1.76; p = 0.013) and CV mortality (SHR, 1.41; 95% CI, 1.02-1.94; p = 0.038) in men but not in women.

Conclusions: Higher serum TMAO levels were independently associated with all-cause and CV mortality in male patients treated with PD.

Keywords: All-cause mortality; Cardiovascular mortality; Peritoneal dialysis; Sex differences; Trimethylamine N-oxide.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Female
  • Humans
  • Male
  • Methylamines / blood*
  • Middle Aged
  • Peritoneal Dialysis / mortality*
  • Prospective Studies
  • Risk Factors
  • Sex Factors

Substances

  • Methylamines
  • trimethyloxamine