Higher serum trimethylamine-N-oxide levels are associated with increased abdominal aortic calcification in hemodialysis patients

Ren Fail. 2022 Dec;44(1):2019-2027. doi: 10.1080/0886022X.2022.2145971.

Abstract

Introduction: Vascular calcification (VC) is high prevalent and predicts cardiovascular mortality in dialysis patients. The mechanisms are not known clearly. Trimethylamine-N-oxide (TMAO), a gut-microbiota derivate metabolite, is also associated with cardiovascular outcomes in hemodialysis (HD) patients. This study aims to evaluate serum TMAO levels and establish their relation to VC in HD patients.

Methods: Serum TMAO concentrations were measured by high-performance liquid chromatography-mass spectrometry. Vascular calcification was evaluated by abdominal aortic calcification (AAC) scores. Taking the AAC score value 5.5 as the cutoff value, the participants were divided into the high AAC score group and the low AAC score group.

Results: A total of 184 HD patients and 39 healthy controls were enrolled in this cross-sectional study. Serum Ln(TMAO) (the natural logarithm of TMAO) concentrations were significantly higher in HD patients than that of control subjects (1.82 ± 0.62 vs. -1.60 ± 0.77, p < 0.001). Compared with the group with low AAC scores, the HD patients with high AAC scores showed significantly higher serum Ln(TMAO) levels (2.09 ± 0.55 vs. 1.67 ± 0.54, p < 0.001). In the multivariate regression analysis, serum Ln(TMAO), HD vintage, with diabetic mellitus, age and plasma intact parathyroid hormone (iPTH) were independent determinant factors for VC in HD patients.

Conclusions: Higher serum TMAO levels, older age, longer HD vintage, higher plasma iPTH and with diabetes mellitus were independent risk factors for VC in HD patients. The underlying mechanism deserves further investigations and the finding hints at a new target for the treatment of VC.

Keywords: Trimethylamine-N-oxide; abdominal aortic calcification; cardiovascular disease; chronic kidney disease; hemodialysis; vascular calcification.

MeSH terms

  • Cross-Sectional Studies
  • Humans
  • Oxides
  • Parathyroid Hormone
  • Renal Dialysis* / adverse effects
  • Vascular Calcification* / etiology

Substances

  • trimethylamine
  • trimethyloxamine
  • Parathyroid Hormone
  • Oxides

Grants and funding

The work was supported by the National Natural Science Foundation (Grant No. 81873619, Grant No. 81570663) to Aihua Zhang, Research Initiation Fund for the Excellent Returned Overseas Scholars of Peking University Third Hospital (Grant No. BYSYLXHG2019007) to Wenling Yang, and the Key Program of Peking University Third Hospital (Grant No. BYSY2018024) to Lian He.