Association of Trimethylamine, Trimethylamine N-oxide, and Dimethylamine with Cardiovascular Risk in Children with Chronic Kidney Disease

Chien-Ning Hsu,Pei-Chen Lu,You-Lin Tain,Sufan Lin,Chih-Yao Hou,Guo-Ping Chang-Chien

doi:10.3390/jcm9020336

Abstract

Chronic kidney disease (CKD) is associated with high risk for cardiovascular disease (CVD). Gut microbiota-dependent metabolites trimethylamine (TMA), trimethylamine N-oxide (TMAO), and dimethylamine (DMA) have been linked to CKD and CVD. We examined whether these methylamines are correlated with cardiovascular risk in CKD children. A total of 115 children and adolescents with CKD stage G1–G4 were enrolled in this cross-sectional study. Children with CKD stage G2–G4 had higher plasma levels of DMA, TMA, and TMAO, but lower urinary levels of DMA and TMAO than those with CKD stage G1. Up to 53% of CKD children and adolescents had blood pressure (BP) abnormalities on 24-h ambulatory BP monitoring (ABPM). Plasma TMA and DMA levels inversely associated with high BP load as well as estimated glomerular filtration rate (eGFR). Additionally, CKD children with an abnormal ABPM profile had decreased abundance of phylum Cyanobacteria, genera Subdoligranulum, Faecalibacterium, Ruminococcus, and Akkermansia. TMA and DMA are superior to TMAO when related to high BP load and other CV risk factors in children and adolescents with early-stage CKD. Our findings highlight that gut microbiota-dependent methylamines are related to BP abnormalities and CV risk in pediatric CKD. Further studies should determine whether these microbial markers can identify children at risk for CKD progression.

Highlights

Chronic kidney disease (CKD) is associated with high risk for cardiovascular disease (CVD), not just for adults and for children [1,2]
The key findings are (1) children with CKD stage G2–G4 had higher plasma levels of DMA, TMA, and trimethylamine N-oxide (TMAO), but lower urinary levels of DMA and TMAO compared to those with CKD stage G1; (2) plasma TMA and DMA levels were inversely associated with high blood pressure (BP) load, and estimated glomerular filtration rate (eGFR); (3) CKD children with abnormal and normal ambulatory blood pressure monitoring (ABPM) associated into two distinct enterotypes; (4) CKD children with an abnormal ABPM profile had decreased abundance of phylum Cyanobacteria, genera Subdoligranulum, Faecalibacterium, Ruminococcus, and Akkermansia; and (5) TMA and DMA are superior to TMAO related to CV risk in early-stage CKD children
In keeping with previous studies showing that left ventricular (LV) mass is greater in CKD children on dialysis and ABPM correlates with LV hypertrophy in CKD children [6,27,28], we observed children with advanced CKD displayed higher degree of LV mass and BP abnormalities

Summary

Introduction

Chronic kidney disease (CKD) is associated with high risk for cardiovascular disease (CVD), not just for adults and for children [1,2]. Heightened efforts are needed to identify CKD children at higher risk for CVD during their lifetimes to develop effective interventions for preemption [3]. Several noninvasive procedures, such as 24-h ambulatory blood pressure monitoring (ABPM) [4], ambulatory arterial stiffness index (AASI) [5], and left ventricular mass [6], are available to evaluate risk for CVD in children with CKD. Emerging evidence has linked higher blood levels of TMAO with a higher risk of CVD [10]

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Discussion

Conclusion