TMAO is Associated with Mortality: Impact of Modestly Impaired Renal Function
Open accessAbstract
Trimethylamine-N-Oxide (TMAO) is a microbiome-related metabolite that is cleared by the kidney and linked to renal function. We explored the relationship between TMAO and all-cause mortality, and determined whether this association was modified by renal function. A prospective study was performed among PREVEND participants to examine associations of plasma TMAO with all-cause mortality. After median follow-up of 8.3 years in 5,469 participants, 322 subjects died. TMAO was positively associated with age, body mass index, type 2 diabetes mellitus and inversely with estimated glomerular filtration rate (eGFR creatcysC)(all P < 0.001). Subjects in the highest versus lowest TMAO quartile had a crude 1.86-fold higher mortality risk (P trend < 0.001). After adjustment for several risk factors, TMAO remained associated with all-cause mortality [HR:1.36 (95% CI, 0.97–1.91),P trend = 0.016]. This association was lost after further adjustment for urinary albumin excretion and eGFR [HR:1.15 (95% CI, 0.81–1.64),P trend = 0.22]. The association of TMAO with mortality was modified by eGFR in crude and age- and sex-adjusted analyses (interaction P = 0.002). When participants were stratified by renal function (eGFR < vs. ≥90 mL/min/1.73 m 2), TMAO was associated with all-cause mortality only in subjects with eGFR <90 mL/min/1.73 m 2 [adjusted HR:1.18 (95% CI, 1.02–1.36),P = 0.023]. In conclusion, TMAO is associated with all-cause mortality, particularly in subjects with eGFR <90 mL/min/1.73 m 2.
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In a larger cohort from the Framingham Heart Study, elevated circulating levels of both choline and TMAO predicted incident development of CKD in subjects with normal renal function at enrollment.
“Then in a larger cohort from the Framingham Heart Study, elevated circulating levels of both choline and TMAO were observed to predict the incident development of CKD in subjects with normal renal function at the time of enrollment and sample collection197.”
From Dietary metabolism, the gut microbiome, and heart failure (2019) · cites this paper as [197]
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Dietary metabolism, the gut microbiome, and heart failure
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- Authors
- Gruppen, E. G., Garcia, E., Connelly, M. A., Jeyarajah, E. J., Otvos, J. D., Bakker, S. J. L., & Dullaart, R. P. F.
- Affiliations
- University Medical Center Groningen (NL)
- LabCorp (United States) (US)
- Corresponding author
- Dullaart, Robin P. F.
- ORCID
- Venue
- Scientific Reports
- Published
- 2017-10-23
- Volume
- 7
- Issue
- 1
- Pages
- 13781-13781
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC5653802
- OpenAlex
- W2765915044
- Cited by
- 146
- References
- 50
- Citations by year
- 2026: 13 · 2025: 20 · 2024: 13 · 2023: 11 · 2022: 25 · 2021: 17 · 2020: 20 · 2019: 16 · 2018: 11
- FWCI
- 11.50
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, cc-by)
- Topics
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Nephrology › Dialysis and Renal Disease Management
- Keywords
- trimethylamine N-oxide, all-cause mortality, renal function, estimated glomerular filtration rate, renal clearance, gut microbiota metabolites, urinary albumin excretion, type 2 diabetes, PREVEND cohort
- MeSH terms
- Adult, Aged, Cardiovascular Diseases, Female, Glomerular Filtration Rate, Humans, Kidney Failure, Chronic, Male, Methylamines, Middle Aged, Prognosis, Prospective Studies, Risk Factors, Biomarkers, Oxidants, Microbiota
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