What type of study is this?

This is a Cohort Study study (also classified as: Quantitative Study).

September 27, 2025

Associations of Plasma Trimethylamine N-Oxide-Related Metabolites with the Development and Progression of Albuminuria: The Multi-Ethnic Study of Atherosclerosis

Puntos clave

TMAO-related metabolites significantly associated with increased albuminuria over 15.7 years follow-up, indicating a novel risk factor.
Highest TMAO levels saw an HR of 1.41 for increased albuminuria, while choline positively linked to all outcomes measured.
Cohort study included 6,723 participants, measuring TMAO and UACR using liquid chromatography over several years.
This research highlights the need for targeting TMAO pathways as potential therapeutic strategies for albuminuria.

Resumen

Background: Trimethylamine N-oxide (TMAO) is a gut microbiota-derived metabolite of dietary phosphatidylcholine and carnitine. Mechanistically, TMAO raises urine albumin to creatinine ratio (UACR). However, little is known in humans about prospective associations between TMAO-related biomarkers and albuminuria, an early, sensitive marker of kidney damage. Methods: We included 6,723 participants with TMAO-related biomarkers and UACR at baseline and follow-up data from July 2000 to May 2019 from a diverse cohort of community-based US adults. Plasma TMAO-related biomarkers (TMAO, γ-butyrobetaine, and crotonobetaine; and secondarily, carnitine, choline, and betaine) were measured using liquid chromatography tandem mass spectrometry at baseline and year five. UACR was measured at up to five visits. The co-primary outcomes were incident increased albuminuria, defined as at least two consecutive UACR measures ≥ 30mg/g during follow-up; and rate of UACR change over time. The secondary outcome was severely increased albuminuria, defined as a new UACR ≥ 300mg/g. Time-varying Cox models assessed associations of biomarkers with incident albuminuria; and linear mixed models with rate of UACR change; adjusting for sociodemographic, lifestyle, diet, and cardiovascular disease risk factors. Results: During a median follow-up of 15.7 years, 648 participants experienced increased albuminuria and 197 experienced severely increased albuminuria. TMAO levels positively associated with both outcomes (highest vs. lowest quintile HR 95%CI = 1.41 1.05-1.89 and 1.73 0.99-3.00, respectively, P-trend<0.01 each). TMAO also associated with greater rate of UACR increase (adjusted percent change per 10-years = 22.1% in the lowest vs. 40.6% in the highest quintile, P-trend<0.001). Crotonobetaine and γ-butyrobetaine levels also associated with rate of UACR increase, as did carnitine, while choline levels positively associated with all three outcomes. Conclusions: TMAO-related gut microbial metabolites may be a novel risk factor for albuminuria and its progression, raising the need to investigate the role of targeting the TMAO pathway on albuminuria.

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Cite This Study

Wang et al. (Thu,) studied this question.

synapsesocial.com/papers/68d7b3ddeebfec0fc5236734 https://doi.org/https://doi.org/10.2215/cjn.0000000812

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