skip to main content
Language:
Search Limited to: Search Limited to: Resource type Show Results with: Show Results with: Search type Index

Gut Microbiota-Dependent Trimethylamine N-Oxide (TMAO) Pathway Contributes to Both Development of Renal Insufficiency and Mortality Risk in Chronic Kidney Disease

Circulation research, 2015-01, Vol.116 (3), p.448-455 [Peer Reviewed Journal]

2015 American Heart Association, Inc. ;2014 American Heart Association, Inc. ;ISSN: 0009-7330 ;EISSN: 1524-4571 ;DOI: 10.1161/CIRCRESAHA.116.305360 ;PMID: 25599331

Full text available

Citations Cited by
  • Title:
    Gut Microbiota-Dependent Trimethylamine N-Oxide (TMAO) Pathway Contributes to Both Development of Renal Insufficiency and Mortality Risk in Chronic Kidney Disease
  • Author: Tang, W.H Wilson ; Wang, Zeneng ; Kennedy, David J ; Wu, Yuping ; Buffa, Jennifer A ; Agatisa-Boyle, Brendan ; Li, Xinmin S ; Levison, Bruce S ; Hazen, Stanley L
  • Subjects: Aged ; Aged, 80 and over ; Animals ; Biomarkers - blood ; Case-Control Studies ; Female ; Humans ; Intestines - microbiology ; Male ; Methylamines - blood ; Methylamines - toxicity ; Mice ; Mice, Inbred C57BL ; Microbiota ; Middle Aged ; Prognosis ; Renal Insufficiency - diagnosis ; Renal Insufficiency - etiology ; Renal Insufficiency, Chronic - diagnosis ; Renal Insufficiency, Chronic - metabolism ; Renal Insufficiency, Chronic - microbiology ; Risk Factors
  • Is Part Of: Circulation research, 2015-01, Vol.116 (3), p.448-455
  • Description: RATIONALE:Trimethylamine-N-oxide (TMAO), a gut microbial-dependent metabolite of dietary choline, phosphatidylcholine (lecithin), and L-carnitine, is elevated in chronic kidney diseases (CKD) and associated with coronary artery disease pathogenesis. OBJECTIVE:To both investigate the clinical prognostic value of TMAO in subjects with versus without CKD, and test the hypothesis that TMAO plays a direct contributory role in the development and progression of renal dysfunction. METHODS AND RESULTS:We first examined the relationship between fasting plasma TMAO and all-cause mortality over 5-year follow-up in 521 stable subjects with CKD (estimated glomerular filtration rate, <60 mL/min per 1.73 m). Median TMAO level among CKD subjects was 7.9 μmol/L (interquartile range, 5.2–12.4 μmol/L), which was markedly higher (P<0.001) than in non-CKD subjects (n=3166). Within CKD subjects, higher (fourth versus first quartile) plasma TMAO level was associated with a 2.8-fold increased mortality risk. After adjustments for traditional risk factors, high-sensitivity C-reactive protein, estimated glomerular filtration rate, elevated TMAO levels remained predictive of 5-year mortality risk (hazard ratio, 1.93; 95% confidence interval, 1.13–3.29; P<0.05). TMAO provided significant incremental prognostic value (net reclassification index, 17.26%; P<0.001 and differences in area under receiver operator characteristic curve, 63.26% versus 65.95%; P=0.036). Among non-CKD subjects, elevated TMAO levels portend poorer prognosis within cohorts of high and low cystatin C. In animal models, elevated dietary choline or TMAO directly led to progressive renal tubulointerstitial fibrosis and dysfunction. CONCLUSIONS:Plasma TMAO levels are both elevated in patients with CKD and portend poorer long-term survival. Chronic dietary exposures that increase TMAO directly contributes to progressive renal fibrosis and dysfunction in animal models.
  • Publisher: United States: American Heart Association, Inc
  • Language: English
  • Identifier: ISSN: 0009-7330
    EISSN: 1524-4571
    DOI: 10.1161/CIRCRESAHA.116.305360
    PMID: 25599331
  • Source: Geneva Foundation Free Medical Journals at publisher websites
    MEDLINE
Back to results list
INSPIRE LIBRARY - TON DUC THANG UNIVERSITY (84-028) 37 755 057 Feedback
19 Nguyen Huu Tho St. Dist.7, HCM thuvien@tdtu.edu.vn

Copyright © 2017 INSPIRE LIBRARY - TON DUC THANG UNIVERSITY

Searching Remote Databases, Please Wait