TABLE 3.
Details of the selected studies and baseline characteristics of the participants in meta-analyses of kidney function indicators in subjects with high concentrations of TMAO versus subjects with low concentrations of TMAO1
| First author | Year | Journal | Country | Design | Subjects, n | Age,2 y | Male, % | Disease status | Sample | Assay | TMAO range,2 μmol/L | Main results |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Tang et al. (17) | 2013 | New Engl J Med | USA | Cohort | 4007 | 63 ± 11 | 65 | CAG | Plasma | LC-MS/MS | 3.7 [2.4–6.2] | eGFR was lower in the high-concentration than in the low-concentration TMAO group (P < 0.001) |
| Tang et al. (50) | 2014 | J Am Coll Cardiol | USA | Cohort | 720 | 66 ± 10 | 59 | Patients with a history of HF | Plasma | LC-MS/MS | 5.0 [3.0–8.5] | eGFR was lower in the high-concentration than in the low-concentration TMAO group (P < 0.001) |
| Tang et al. (49) | 2017 | Clin Chem | USA | Cohort | 1216 | 64.4 ± 10.2 | 58 | Type 2 DM | Plasma | LC-MS/MS | 4.4 [2.8–7.7] | eGFR was lower in T3 of TMAO than in T1 (P < 0.001) |
| Stubbs et al. (27) | 2016 | J Am Soc Nephrol | USA | Cohort | 220 | 69.7 ± 10.3 | 42.7 | CKD | Serum | UHPLC-MS/MS | 6.9 [4.8–10.9] | eGFR was lower in T3 of TMAO than in T1 and T2 (P < 0.001) |
| Stubbs et al. (52) | 2019 | Clin J Am Soc Nephrol | Global | RCT | 1243 | 54 ± 14 | 60 | ESKD | Serum | UPLC-MS | 0.91–7.01 | No significant difference in BUN was observed between groups |
| Nie et al. (21) | 2018 | Stroke | China | Case-control | 1244 | 45–75 | 47 | Hypertensive | Serum | LC-MS/MS | T1 <1.79, T3 ≥3.19 | eGFR was lower in T3 of TMAO than in T1 (P < 0.001) |
| Gruppen et al. (58) | 2017 | Sci Rep | Netherlands | Cohort | 5469 | 53.5 ± 12 | 48.7 | Healthy adults | Plasma | LC-MS/MS | 3.2 [1.70–5.70] | eGFR was lower and UAER was higher in Q4 of TMAO than in Q1 (P < 0.001, both) |
| Svingen et al. (20) | 2018 | Int J Cardiol | Norway | Cohort | 4141 | 51–73 | 72 | Suspected stable angina | Plasma | LC-MS/MS | 9.25 [2.2–23.5] | eGFR was lower in Q4 of TMAO than in Q1 (P < 0.0001) |
| Svingen et al. (20) | 2018 | Int J Cardiol | Norway | Cohort | 3143 | 72 [71–73] | 43 | Healthy adults | Plasma | LC-MS/MS | 8.82 [2.6–31.6] | eGFR was lower in Q4 of TMAO than in Q1 (P < 0.0001) |
| Randrianarisoa et al. (54) | 2016 | Int J Cardiol | Germany | Cross-sectional | 220 | 46 ± 11 | 41 | Healthy adults | Serum | LC-MS/MS | T1: 2.13 ± 0.94, T3: 3.84 ± 2.06 | No significant difference in eGFR was observed between groups |
| Winther et al. (48) | 2019 | Diabetes Care | Denmark | Cohort | 1159 | 46 ± 13 | 58 | Type 1 DM | Plasma | LC-MS/MS | 5.7 [3.8–9.9] | eGFR was lower and UAER was higher in Q4 of TMAO than in Q1 (P < 0.001, both) |
| Krüger et al. (57) | 2017 | Mol Nutr Food Res | Germany | Cross-sectional | 297 | 47.5 ± 17.2 | 57.6 | Healthy adults | Plasma | LC-MS/MS | Q1 <2.91, Q4 >6.02 | eGFR was lower in Q4 of TMAO than in Q1 (P < 0.0001) |
| Meyer et al. (55) | 2016 | J Am Heart Assoc | USA | Cohort | 817 | 33–55 | 43 | Healthy adults | Plasma | HPLC-MS/MS | 2.6 [1.8–4.2] | eGFR was lower in Q4 of TMAO than in Q1 (P = 0.002); no difference in UACR was observed between groups (P = 0.554) |
| Suzuki et al. (19) | 2016 | Heart | England | Cohort | 972 | 78 [69–84] | 61 | AHF | Plasma | UPLC-MS/MS | 5.6 [3.4–10.5] | eGFR was lower and blood urea and sCr were higher in the high-concentration than in the low-concentration TMAO group (P < 0.0005, all) |
| Suzuki et al. (51) | 2017 | Clin Chem | England | Cohort | 1079 | 65 [57–77] | 72 | Acute MI | Plasma | UPLC-MS/MS | 3.7 [4.6–6.4] | eGFR was lower and blood urea was higher in T3 of TMAO than in T1 (P < 0.0005, both) |
| Senthong et al. (53) | 2016 | J Am Heart Assoc | USA | Cohort | 2235 | 63 ± 11 | 71 | Stable CAD | Plasma | HPLC-MS/MS | 3.8 [2.5–6.5] | eGFR was lower in Q4 of TMAO than in other quartiles (P < 0.001) |
| Matsuzawa et al. (56) | 2019 | Sci Rep | Japan | Cross-sectional | 112 | 63 [56–71] | 88 | STEMI | Plasma | LC-MS/MS | 6.76 [3.82–12.5] | No significant difference in eGFR was observed between groups (P = 0.11) |
| Zhou et al. (47) | 2020 | ESC Heart Fail | China | Cohort | 1208 | 73 [64–80] | 68.5 | CHF patients after MI | Plasma | UHPLC | lower <4.5, higher ≥4.5 | eGFR was lower in the high-concentration than in the low-concentration TMAO group (P < 0.001) |
In this analysis, if the original study reported circulating TMAO concentrations as quartiles or tertiles, the high concentration of TMAO included the highest layer of TMAO concentration, and the other layers were classified into the low concentration of TMAO. AHF, acute heart failure; BUN, blood urea nitrogen; CAD, coronary-artery disease; CAG, coronary angiography; CHF, chronic heart failure; CKD, chronic kidney disease; DM, diabetes mellitus; eGFR, estimated glomerular filtration rate; ESKD, end-stage kidney disease; HF, heart failure; LC-MS/MS, LC-tandem MS; MI, myocardial infarction; Q1, quartile 1; Q4, quartile 4; RCT, randomized controlled trial; sCr, serum creatinine; STEMI, ST-segment elevation myocardial infarction; T1, tertile 1; T2, tertile 2; T3, tertile 3; TMAO, trimethylamine N-oxide; UACR, urine albumin-to-creatinine ratio; UAER, urine albumin excretion rate; UHPLC, ultra-high-performance LC; UPLC, ultra-performance LC.
Values are mean ± SD, range, or median [IQR].