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

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.