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

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Gut Microbiota-Dependent Trimethylamine N-Oxide (TMAO) Pathway Contributes to Both Development of Renal Insufficiency and Mortality Risk in Chronic Kidney DiseaseNovelty and Significance by W.H. Wilson Tang, Zeneng Wang, David J. Kennedy, Yuping Wu, Jennifer A. Buffa, Brendan Agatisa-Boyle, Xinmin S. Li, Bruce S. Levison, and Stanley L. Hazen Circulation Research Volume 116(3):448-455 January 30, 2015 Copyright © American Heart Association, Inc. All rights reserved.

Prognostic Value of plasma trimethylamine N-oxide (TMAO) levels in the chronic kidney disease (CKD) Cohort. Prognostic Value of plasma trimethylamine N-oxide (TMAO) levels in the chronic kidney disease (CKD) Cohort. In a cohort of stable patients undergoing elective diagnostic coronary evaluation, subjects with underlying CKD Stage 3+ (n=521) demonstrated higher levels of fasting plasma TMAO than those with no CKD (n=3,166; P<0.01; A). Increasing quartiles fasting plasma TMAO levels portend increased risk for all-cause mortality at 5 years in patients with CKD (n=521; B). W.H. Wilson Tang et al. Circ Res. 2015;116:448-455 Copyright © American Heart Association, Inc. All rights reserved.

Comparative prognostic value of plasma trimethylamine-N-oxide (TMAO) and Cystatin C (CysC) in the non-chronic kidney disease (CKD) cohort. Comparative prognostic value of plasma trimethylamine-N-oxide (TMAO) and Cystatin C (CysC) in the non-chronic kidney disease (CKD) cohort. Subjects with elevated CysC (≥0.9 mg/dL) and TMAO (≥3.4 μmol/L) had the highest 5-year mortality risk in this non-CKD cohort (n=3188). W.H. Wilson Tang et al. Circ Res. 2015;116:448-455 Copyright © American Heart Association, Inc. All rights reserved.

Dietary choline/trimethylamine-N-oxide (TMAO) exposure contributes to progressive renal fibrosis in murine model. Dietary choline/trimethylamine-N-oxide (TMAO) exposure contributes to progressive renal fibrosis in murine model. Plasma TMAO (A) levels are increased after 6 week feeding TMAO (0.12%), or Choline (1.0%) diets vs Chow (0.08% choline) fed mice. Representative Mason trichrome histology (B) quantitative morphometry and its relationship with TMAO levels (C), and SMAD3 activation by phosphorylation at serine 423/425 (D) and its relationship with TMAO levels (E) in mouse kidneys after 6 week feeding of Chow (0.08% choline), TMAO (0.12%), and Choline (1.0%) diets. Scale bar, 100 um. **P<0.01 vs Chow, n≥5 mice per group. W.H. Wilson Tang et al. Circ Res. 2015;116:448-455 Copyright © American Heart Association, Inc. All rights reserved.

Dietary choline/trimethylamine-N-oxide (TMAO) exposure contributes to progressive renal injury and dysfunction in murine model. Dietary choline/trimethylamine-N-oxide (TMAO) exposure contributes to progressive renal injury and dysfunction in murine model. Immunoblot of kidney injury molecular 1 (KIM-1) expression (A) and its relationship with TMAO levels (B) in mouse kidneys after 6 week feeding of chow (0.08% choline), TMAO (0.12%), and choline (1.0%) diets. Also shown are plasma cystatin C levels (C) after 16 week feeding of Chow, TMAO (0.12%), and Choline (1.0%) diets. **P<0.01 vs Chow, n≥5 mice per group. W.H. Wilson Tang et al. Circ Res. 2015;116:448-455 Copyright © American Heart Association, Inc. All rights reserved.