The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.
Serum Trimethylamine-N-Oxide Is Strongly Related to Renal Function and Predicts Outcome in Chronic Kidney Disease
Open accessAbstract
BACKGROUND: The microbial metabolite Trimethylamine-N-oxide (TMAO) has been linked to adverse cardiovascular outcome and mortality in the general population. OBJECTIVE: To assess the contribution of TMAO to inflammation and mortality in chronic kidney disease (CKD) patients ranging from mild-moderate to end-stage disease and 1) associations with glomerular filtration rate (GFR) 2) effect of dialysis and renal transplantation (Rtx) 3) association with inflammatory biomarkers and 4) its predictive value for all-cause mortality. METHODS: Levels of metabolites were quantified by a novel liquid chromatography/tandem mass spectrometry-based method in fasting plasma samples from 80 controls and 179 CKD 3-5 patients. Comorbidities, nutritional status, biomarkers of inflammation and GFR were assessed. RESULTS: GFR was the dominant variable affecting TMAO (β = -0.41; p<0.001), choline (β = -0.38; p<0.001), and betaine (β = 0.45; p<0.001) levels. A longitudinal study of 74 CKD 5 patients starting renal replacement therapy demonstrated that whereas dialysis treatment did not affect TMAO, Rtx reduced levels of TMAO to that of controls (p<0.001). Following Rtx choline and betaine levels continued to increase. In CKD 3-5, TMAO levels were associated with IL-6 (Rho = 0.42; p<0.0001), fibrinogen (Rho = 0.43; p<0.0001) and hsCRP (Rho = 0.17; p = 0.022). Higher TMAO levels were associated with an increased risk for all-cause mortality that remained significant after multivariate adjustment (HR 4.32, 95% CI 1.32-14.2; p = 0.016). CONCLUSION: Elevated TMAO levels are strongly associated with degree of renal function in CKD and normalize after renal transplantation. TMAO levels correlates with increased systemic inflammation and is an independent predictor of mortality in CKD 3-5 patients.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“levels are higher the more the glomerular filtration rate GFR is reduced [49]”
From Implication of Trimethylamine N-Oxide (TMAO) in Disease: Potential Biomarker or New Therapeutic Target (2018) · cites this paper as [49]
In the citing paper
“Nonetheless, median values of TMAO concentrations in healthy individuals were reported as ranges of 3 to 6 μmol/L,8, 17, 18, 19 and the study by Shafi et al22 consisted of hemodialysis patients with the substantially high mean vale of TMAO (101.9 μmol/L among total participants).”
From Gut Microbiota Metabolites and Risk of Major Adverse Cardiovascular Disease Events and Death: A Systematic Review and Meta‐Analysis of Prospective Studies (2017) · cites this paper as [18]
In the citing paper
“In 179 CKD stage 3-5 patients, the GFR and impaired renal function were the main variables affecting plasma TMAO concentrations (81).”
From Trimethylamine N -Oxide, the Microbiome, and Heart and Kidney Disease (2017) · cites this paper as [81]
In the citing paper
“Serum concentration of TMAO was inversely associated with eGFR and was markedly higher in patients receiving dialysis (59,81); hemodialysis efficiently removed TMAO from blood (8).”
From Trimethylamine N -Oxide, the Microbiome, and Heart and Kidney Disease (2017) · cites this paper as [81]
In the citing paper
“Increased TMAO concentrations were associated with systemic inflammatory markers and predicted a reduced fiveyear survival (81).”
From Trimethylamine N -Oxide, the Microbiome, and Heart and Kidney Disease (2017) · cites this paper as [81]
In the citing paper
“Renal transplantation corrects the high plasma TMAO concentrations seen in renal failure (81,106).”
From Trimethylamine N -Oxide, the Microbiome, and Heart and Kidney Disease (2017) · cites this paper as [81]
In the citing paper
“TMAO levels increase with decreasing levels of kidney function and is associated with mortality in patients with chronic kidney disease.”
From Trimethylamine N-oxide: the good, the bad and the unknown. (2016) · cites this paper as [27]
In the citing paper
“Missailidis et al. measured plasma concentration of TMAO in 80 controls and 179 CKD patients and reported that that elevated TMAO levels are strongly associated with degree of renal function [27].”
From Trimethylamine N-oxide: the good, the bad and the unknown. (2016) · cites this paper as [27]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Ahmed, A., Jorna, T., & Bhandari, S. (2016) · The Nephron journals/Nephron journals · doi:10.1159/000447068 · Cited by 11,782
Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease
Wang, Z., Klipfell, E., Bennett, B. J., Koeth, R., Levison, B. S., DuGar, B., Feldstein, A. E., Britt, E. B., Fu, X., Chung, Y.-M., et al. (2011) · Nature · doi:10.1038/nature09922 · Cited by 5,597
Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis
Koeth, R. A., Wang, Z., Levison, B. S., Buffa, J. A., Org, E., Sheehy, B. T., Britt, E. B., Fu, X., Wu, Y., Li, L., et al. (2013) · Nature Medicine · doi:10.1038/nm.3145 · Cited by 4,386
Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk
Tang, W. H. W., Wang, Z., Levison, B. S., Koeth, R. A., Britt, E. B., Fu, X., Wu, Y., & Hazen, S. L. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1109400 · Cited by 3,400
Strong association between malnutrition, inflammation, and atherosclerosis in chronic renal failure
Stenvinkel, P., Heimbürger, O., Paultre, F., Diczfalusy, U., Wang, T., Berglund, L., & Jogestrand, T. (1999) · Kidney International · doi:10.1046/j.1523-1755.1999.00422.x · Cited by 1,767
Self-citationFox, C. S., Matsushita, K., Woodward, M., Bilo, H. J., Chalmers, J., Heerspink, H. J. L., Lee, B. J., Perkins, R. M., Rossing, P., Sairenchi, T., et al. (2012) · The Lancet · doi:10.1016/s0140-6736(12)61350-6 · Cited by 1,401
Tang, W. H. W., Wang, Z., Kennedy, D. J., Wu, Y., Buffa, J. A., Agatisa-Boyle, B., Li, X. S., Levison, B. S., & Hazen, S. L. (2015) · Circulation Research · doi:10.1161/circresaha.116.305360 · Cited by 1,223
Chronic kidney disease alters intestinal microbial flora
Vaziri, N. D., Wong, J., Pahl, M., Piceno, Y. M., Yuan, J., DeSantis, T. Z., Ni, Z., Nguyen, T.-H., & Andersen, G. L. (2013) · Kidney International · doi:10.1038/ki.2012.345 · Cited by 1,164
Bennett, B. J., Vallim, T. Q. D. A., Wang, Z., Shih, D. M., Meng, Y., Gregory, J., Allayee, H., Lee, R., Graham, M., Crooke, R., et al. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2012.12.011 · Cited by 1,070
The Gut Microbiome, Kidney Disease, and Targeted Interventions
Ramezani, A., & Raj, D. S. (2013) · Journal of the American Society of Nephrology · doi:10.1681/asn.2013080905 · Cited by 773
Flagged first, then by citations
Cited by
Sorted by citations
Items 301–340 of 340
Effects of Trimethylamine N-Oxide on Mouse Embryonic Stem Cell Properties
Barron, C. (2020) · VTechWorks (Virginia Tech)
Macpherson, M. E. (2020) · NORA - Norwegian Open Research Archives
류주희 (2019) · Seoul National University Open Repository (Seoul National University)
Matsumoto, T., Taguchi, N., Yoshioka, M., Osada, T., Taguchi, K., & Kobayashi, T. (2022) · Folia Pharmacologica Japonica · doi:10.1254/fpj.22029
The Role of The Metabolism/Exposome in Chronic Kidney Disease: Discovery for Precision Nutrition
Pathmasiri, W., Schroder, M., McRitchie, S., & Sumner, S. (2022) · Springer eBooks · doi:10.1007/978-3-031-11942-2_3
MiRNAs as epigenetic regulators for gut microbiome
Singhal, S., & Rani, V. (2023) · Elsevier eBooks · doi:10.1016/b978-0-323-99521-4.00016-7
The role of the gut micro biota in kidney disease
López, J. L. D., de la Cruz, Y., Aviles, G. F. G., Puello, L., & Bustamante, N. P. G. (2023) · GSC Advanced Research and Reviews · doi:10.30574/gscarr.2023.14.3.0106
Zou, W., Liu, Y., Zhang, W., Shen, W., & Lin, B. (2023) · Research Square · doi:10.21203/rs.3.rs-2707130/v1
Coutinho‐Wolino, K. S., Cruz, B. O. D., Cardozo, L., Mesquita, C. T., Mafra, D., & Stockler‐Pinto, M. B. (2023) · DEMETRA Alimentação Nutrição & Saúde · doi:10.12957/demetra.2023.73690
THE ROLE OF THE INTESTINAL MICROBIOTA METABOLITE TMAO IN THE PATHOGENESIS OF VARIOUS DISEASES
Samoilova-Bedych, N., Laryushina, Е. М., Marchenko, A., & Сейсенбекова, А. К. (2024) · Farmaciâ Kazahstana · doi:10.53511/pharmkaz.2024.25.65.015
Sinyushkina, S. D., Gorinova, A. V., Belousova, A. S., Sorokina, Y. А., & Занозина, О. В. (2024) · Meditsinskiy sovet = Medical Council · doi:10.21518/ms2024-386
Yang, H.-H., Chen, Y.-C., Liu, C., & Hsu, B. (2024) · Medical Science Monitor · doi:10.12659/msm.947197
The Role of Microbiome in Metabolic Pattern Changes
Akool, E., Shatat, A.-A. S., & Balah, A. (2025) · Springer eBooks · doi:10.1007/978-981-96-1305-2_13
Kang, S.-J., Kim, W.-G., Kim, K., Choi, C.-H., Park, J., Kang, S.-J., Lee, C., Do, Y. J., & Ro, W. (2025) · Animals · doi:10.3390/ani15152170
Laučytė-Cibulskienė, A., Ward, L. J., Ebert, T., Tosti, G., Tucci, C., Hernandez, L. N., Kautzky‐Willer, A., Herrero, M.-T., Norris, C. M., Pilote, L., et al. (2021) · Figshare · doi:10.6084/m9.figshare.16625590
Self-citationAziz, F., Tripolt, N. J., Pferschy, P. N., Kolesnik, E., Mangge, H., Curcic, P., Hermann, M., Meinitzer, A., von Lewinski, D., & Sourij, H. (2023) · Figshare · doi:10.6084/m9.figshare.23722344
Naghipour, S., Cox, A. J., Fisher, J. J., Plan, M. R., Stark, T., West, N., Peart, J. N., Headrick, J. P., & Toit, E. F. D. (2024) · Figshare · doi:10.6084/m9.figshare.26734986
Xiong, X., Zhou, J., Fu, Q., Xu, X., Wei, S., Yang, S., & Chen, B. (2022) · Figshare · doi:10.6084/m9.figshare.20353468
Suchecka, N. A., Popławska, P., Obrycka, P., Frątczak, A., Tokarz, E., Soczyńska, J., & Woźniak, S. (2026) · Biomedicines · doi:10.3390/biomedicines14020287
Multi-Omics Mechanisms of Trimethylamine Oxide and Cardiovascular Disease: A Review
Yu, H., & Li, F. (2026) · Reviews in Cardiovascular Medicine · doi:10.31083/rcm44420
Ren, B., Wang, H., Cao, Y., Zhang, Z., Wu, X., Ji, S., & Zhao, J. (2026) · Frontiers in Microbiology · doi:10.3389/fmicb.2026.1726262
Xu, J., Lin, S., Zhang, B. R., Feng, X., Liu, L., Huang, L., Liao, M., Li, J., Yang, K., Wang, J., et al. (2026) · Research Square · doi:10.21203/rs.3.rs-9256291/v1
Trimethylamine N-oxide as a key microbial mediator in the progression of diabetic kidney disease
Kashiv, P., Balwani, M. R., Pasari, A. S., Saxena, K., & Kute, V. B. (2026) · World Journal of Nephrology · doi:10.5527/wjn.v15.i2.117355
The role of mitochondria in the gut-kidney axis: implications for kidney health
Hu, Q., Jin, H., Hu, L., & Li, X. (2026) · Frontiers in Pharmacology · doi:10.3389/fphar.2026.1851705
Rutka, B., Danieluk, A., Krata, N., & Mucha, K. (2026) · Journal of Clinical Medicine · doi:10.3390/jcm15135213
Elevated plasma TMAO levels associated with all-cause mortality in CAD patients in South China
Zhang, H., Peng, Y., Lu, X.-Y., Li, Y. Y., Li, W., Hu, Y., Li, W., & Chen, B.-L. (2026) · BMC Cardiovascular Disorders · doi:10.1186/s12872-026-06214-9
Raghavender, G., Chiwhane, A., Parepalli, A., Krishna, K. V. V., & Alluri, J. V. (2026) · Indian Journal of Medical Specialities · doi:10.4103/injms.injms_269_25
DiDonato, J. A., Weeks, T. L., Gupta, N., Mallela, D. P., Buffa, J. A., Wang, Z., Li, X. S., Anderson, J. T., Fu, X., Sangwan, N., et al. (2026) · Journal of the American Society of Nephrology · doi:10.1681/asn.0000001171
Tang, J., Zaretsky, J. A., Labajo, J. D., Shaqo, A., Dakroub, H., Shelp, G. V., Poole, E. M., Burns, S. E., & Cho, C. E. (2026) · iScience · doi:10.1016/j.isci.2026.116720
Currò, M., Bertuccio, M. P., Ientile, R., & Caccamo, D. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27177517
Strizzi, C. T., Hernandez, L. N., Arefin, S., Cantaluppi, V., Pesce, F., Stenvinkel, P., & Kublickiene, K. R. (2026) · European Journal of Internal Medicine · doi:10.1016/j.ejim.2026.107178
Self-citationDonath-Miklos, I., Știrbu, O., Popețiu, R. O., Crişan, A. S., Vulciu, P. A., Coman, R. A., Avram, C. R., Roman, D. R., Bugari, R. A., Zdremtan, D., et al. (2026) · Diagnostics · doi:10.3390/diagnostics16193084
Xu, J., Qi, Q., & Wang, Q. (2026) · Synthetic and Systems Biotechnology · doi:10.1016/j.synbio.2026.09.006
Altahrawi, A. Y., Sofi, F., Kanjwal, Z., & Shah, Z. A. (2026) · Cells · doi:10.3390/cells15201845
Czarnowski, P., Czajkowska, A., Rubik, J., & Kocur, A. (2026) · Clinica Chimica Acta · doi:10.1016/j.cca.2026.122894
Chong, L., Rampersaud, H., Rao, D. A., Gujare, I., Makhijani, A., Kim, D., Levy, E., Beatty, B. L., & Kobayashi, S. (2026) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00584.2026
Metadata
- Authors
- Missailidis, C., Hällqvist, J., Qureshi, A. R., Barany, P., Heimbürger, O., Lindholm, B., Stenvinkel, P., & Bergman, P.
- Affiliations
- Karolinska University Hospital (SE)
- Swedish University of Agricultural Sciences (SE)
- Corresponding author
- Missailidis, Catharina
- ORCID
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2016-01-11
- Volume
- 11
- Issue
- 1
- Pages
- e0141738
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC4709190
- OpenAlex
- W2232990799
- Cited by
- 338
- References
- 34
- Citations by year
- 2026: 22 · 2025: 32 · 2024: 27 · 2023: 36 · 2022: 44 · 2021: 34 · 2020: 42 · 2019: 33 · 2018: 28 · 2017: 27 · 2016: 13
- FWCI
- 34.20
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- Stockholms Läns Landsting (2013-0317)
- Vetenskapsrådet
- Topics
- Health Sciences › Medicine › Nephrology › Dialysis and Renal Disease Management
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Keywords
- trimethylamine N-oxide, chronic kidney disease, glomerular filtration rate, renal function, kidney transplantation, dialysis, all-cause mortality, systemic inflammation, interleukin-6, fibrinogen, C-reactive protein, choline, betaine, microbial metabolites, prognostic factors
- MeSH terms
- Adult, Aged, Betaine, C-Reactive Protein, Cardiovascular Diseases, Choline, Female, Fibrinogen, Glomerular Filtration Rate, Renal Dialysis, Humans, Inflammation, Longitudinal Studies, Male, Methylamines, Middle Aged, Prognosis, Severity of Illness Index, Biomarkers, Interleukin-6, Multivariate Analysis, Survival Analysis, Kidney Transplantation, Renal Insufficiency, Chronic
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
