Advanced chronic kidney disease populations have elevated trimethylamine N-oxide levels associated with increased cardiovascular events
Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved..
Cardiovascular disease is more common in patients with chronic kidney disease (CKD), and traditional risk factors do not adequately predict those at risk for cardiovascular (CV) events. Recent evidence suggests elevated trimethylamine N-oxide (TMAO), created by gut microflora from dietary L-carnitine and choline, is associated with CV events. We investigated the relationship of TMAO levels in patients with stages 3b and 4 CKD to ischemic CV events using the CanPREDDICT cohort, a Canada-wide observational study with prospective 3-year follow-up of adjudicated CV events. Baseline samples were obtained for 2529 CKD patients. TMAO, choline, and L-carnitine levels were measured using tandem mass spectrometry. Baseline median TMAO level was high for the whole cohort (20.41 μM; interquartile range [IQR]: 12.82-32.70 μM). TMAO was independently associated with CV events (hazard ratio 1.23; 95% confidence interval: 1.06-1.42 / 1 SD lnTMAO) after adjusting for all potential CV risk factors. Those in the highest TMAO quartile had significantly higher risk of CV events (adjusted hazard ratio 1.59; 95% confidence interval: 1.04-2.43; P = 0.0351) in the analysis of recurring ischemic events. Among those with stage 3b CKD (hazard ratio 1.45; 95% confidence interval: 1.12-1.87 / 1 SD lnTMAO), independent of kidney function, TMAO levels identified those at highest risk for events. Our results suggest that TMAO may represent a new potentially modifiable CV risk factor for CKD patients. Further studies are needed to determine sources of variability and if lowering of TMAO reduces CV risk in CKD.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2016 |
|---|---|
| Erschienen: |
2016 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:89 |
|---|---|
| Enthalten in: |
Kidney international - 89(2016), 5 vom: 13. Mai, Seite 1144-1152 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Kim, Richard B [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 17.01.2017 Date Revised 16.03.2022 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.kint.2016.01.014 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM259448125 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM259448125 | ||
| 003 | DE-627 | ||
| 005 | 20231224191221.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231224s2016 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.kint.2016.01.014 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0864.xml |
| 035 | |a (DE-627)NLM259448125 | ||
| 035 | |a (NLM)27083288 | ||
| 035 | |a (PII)S0085-2538(16)00295-7 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Kim, Richard B |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Advanced chronic kidney disease populations have elevated trimethylamine N-oxide levels associated with increased cardiovascular events |
| 264 | 1 | |c 2016 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 17.01.2017 | ||
| 500 | |a Date Revised 16.03.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a Cardiovascular disease is more common in patients with chronic kidney disease (CKD), and traditional risk factors do not adequately predict those at risk for cardiovascular (CV) events. Recent evidence suggests elevated trimethylamine N-oxide (TMAO), created by gut microflora from dietary L-carnitine and choline, is associated with CV events. We investigated the relationship of TMAO levels in patients with stages 3b and 4 CKD to ischemic CV events using the CanPREDDICT cohort, a Canada-wide observational study with prospective 3-year follow-up of adjudicated CV events. Baseline samples were obtained for 2529 CKD patients. TMAO, choline, and L-carnitine levels were measured using tandem mass spectrometry. Baseline median TMAO level was high for the whole cohort (20.41 μM; interquartile range [IQR]: 12.82-32.70 μM). TMAO was independently associated with CV events (hazard ratio 1.23; 95% confidence interval: 1.06-1.42 / 1 SD lnTMAO) after adjusting for all potential CV risk factors. Those in the highest TMAO quartile had significantly higher risk of CV events (adjusted hazard ratio 1.59; 95% confidence interval: 1.04-2.43; P = 0.0351) in the analysis of recurring ischemic events. Among those with stage 3b CKD (hazard ratio 1.45; 95% confidence interval: 1.12-1.87 / 1 SD lnTMAO), independent of kidney function, TMAO levels identified those at highest risk for events. Our results suggest that TMAO may represent a new potentially modifiable CV risk factor for CKD patients. Further studies are needed to determine sources of variability and if lowering of TMAO reduces CV risk in CKD | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Multicenter Study | |
| 650 | 4 | |a Observational Study | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a cardiovascular risk | |
| 650 | 4 | |a chronic kidney disease | |
| 650 | 4 | |a trimethylamine N-oxide | |
| 650 | 7 | |a Biomarkers |2 NLM | |
| 650 | 7 | |a Methylamines |2 NLM | |
| 650 | 7 | |a trimethyloxamine |2 NLM | |
| 650 | 7 | |a FLD0K1SJ1A |2 NLM | |
| 700 | 1 | |a Morse, Bridget L |e verfasserin |4 aut | |
| 700 | 1 | |a Djurdjev, Ognjenka |e verfasserin |4 aut | |
| 700 | 1 | |a Tang, Mila |e verfasserin |4 aut | |
| 700 | 1 | |a Muirhead, Norman |e verfasserin |4 aut | |
| 700 | 1 | |a Barrett, Brendan |e verfasserin |4 aut | |
| 700 | 1 | |a Holmes, Daniel T |e verfasserin |4 aut | |
| 700 | 1 | |a Madore, Francois |e verfasserin |4 aut | |
| 700 | 1 | |a Clase, Catherine M |e verfasserin |4 aut | |
| 700 | 1 | |a Rigatto, Claudio |e verfasserin |4 aut | |
| 700 | 1 | |a Levin, Adeera |e verfasserin |4 aut | |
| 700 | 0 | |a CanPREDDICT Investigators |e verfasserin |4 aut | |
| 700 | 1 | |a Agharazii, Mohsen |e investigator |4 oth | |
| 700 | 1 | |a Blouin, Joanne |e investigator |4 oth | |
| 700 | 1 | |a Samson, France |e investigator |4 oth | |
| 700 | 1 | |a Akbarii, Ayub |e investigator |4 oth | |
| 700 | 1 | |a Cheesman, Judy |e investigator |4 oth | |
| 700 | 1 | |a Courtney, Jennilea |e investigator |4 oth | |
| 700 | 1 | |a Hamer, Sabrina |e investigator |4 oth | |
| 700 | 1 | |a Delic, Edita |e investigator |4 oth | |
| 700 | 1 | |a Cronin, Valerie |e investigator |4 oth | |
| 700 | 1 | |a Barré, Paul |e investigator |4 oth | |
| 700 | 1 | |a Golden, Jeffrey |e investigator |4 oth | |
| 700 | 1 | |a Barrett, Brendan |e investigator |4 oth | |
| 700 | 1 | |a Langille, Elizabeth |e investigator |4 oth | |
| 700 | 1 | |a Adams, Sandra |e investigator |4 oth | |
| 700 | 1 | |a Morgan, Janet |e investigator |4 oth | |
| 700 | 1 | |a Clase, Catherine |e investigator |4 oth | |
| 700 | 1 | |a Moreau, Cathy |e investigator |4 oth | |
| 700 | 1 | |a Cooper, Susan |e investigator |4 oth | |
| 700 | 1 | |a Forzley, Brian |e investigator |4 oth | |
| 700 | 1 | |a Caron, Susan |e investigator |4 oth | |
| 700 | 1 | |a Granger, Shauna |e investigator |4 oth | |
| 700 | 1 | |a Valley, Susan |e investigator |4 oth | |
| 700 | 1 | |a Sather, Helen |e investigator |4 oth | |
| 700 | 1 | |a Cournoyer, Serge |e investigator |4 oth | |
| 700 | 1 | |a Menard, Lorraine |e investigator |4 oth | |
| 700 | 1 | |a Roy, Michèle |e investigator |4 oth | |
| 700 | 1 | |a Skidmore, Hélène |e investigator |4 oth | |
| 700 | 1 | |a Beaudry, Dolores |e investigator |4 oth | |
| 700 | 1 | |a Dionne, Janis |e investigator |4 oth | |
| 700 | 1 | |a Chow, Josephine |e investigator |4 oth | |
| 700 | 1 | |a Sahraei, Valla |e investigator |4 oth | |
| 700 | 1 | |a Donnelly, Sandra |e investigator |4 oth | |
| 700 | 1 | |a Dacouris, Niki |e investigator |4 oth | |
| 700 | 1 | |a Marticorena, Rosa |e investigator |4 oth | |
| 700 | 1 | |a Hemmelgarn, Brenda |e investigator |4 oth | |
| 700 | 1 | |a Gulewich, Sharon |e investigator |4 oth | |
| 700 | 1 | |a Hamilton, Troy |e investigator |4 oth | |
| 700 | 1 | |a Keown, Paul |e investigator |4 oth | |
| 700 | 1 | |a Zalunardo, Nadia |e investigator |4 oth | |
| 700 | 1 | |a Rogers, Daniel |e investigator |4 oth | |
| 700 | 1 | |a Tut, Reena |e investigator |4 oth | |
| 700 | 1 | |a Paquette, Matthew |e investigator |4 oth | |
| 700 | 1 | |a Yung, Rossitta |e investigator |4 oth | |
| 700 | 1 | |a Levin, Adeera |e investigator |4 oth | |
| 700 | 1 | |a Ferguson, Nancy |e investigator |4 oth | |
| 700 | 1 | |a Tang, Mila |e investigator |4 oth | |
| 700 | 1 | |a Chiu, Helen |e investigator |4 oth | |
| 700 | 1 | |a Carlson, Kathleen |e investigator |4 oth | |
| 700 | 1 | |a Sioson, Lina |e investigator |4 oth | |
| 700 | 1 | |a Perry, Taylor |e investigator |4 oth | |
| 700 | 1 | |a Sheriff, Zainab |e investigator |4 oth | |
| 700 | 1 | |a Rozen, Naama |e investigator |4 oth | |
| 700 | 1 | |a Lok, Charmaine |e investigator |4 oth | |
| 700 | 1 | |a Cross, Michelle |e investigator |4 oth | |
| 700 | 1 | |a Forrester, Cathy |e investigator |4 oth | |
| 700 | 1 | |a Cotoi, Alexandra |e investigator |4 oth | |
| 700 | 1 | |a Madore, François |e investigator |4 oth | |
| 700 | 1 | |a Maltais, Manon |e investigator |4 oth | |
| 700 | 1 | |a Moist, Louise |e investigator |4 oth | |
| 700 | 1 | |a Gallo, Kerri |e investigator |4 oth | |
| 700 | 1 | |a Langford, Sarah |e investigator |4 oth | |
| 700 | 1 | |a Slamen, Leah |e investigator |4 oth | |
| 700 | 1 | |a Cram, Danielle |e investigator |4 oth | |
| 700 | 1 | |a Muirhead, Norman |e investigator |4 oth | |
| 700 | 1 | |a Edgar, Mary Jeanne |e investigator |4 oth | |
| 700 | 1 | |a Gray, Taylor |e investigator |4 oth | |
| 700 | 1 | |a Edgar, Cameron |e investigator |4 oth | |
| 700 | 1 | |a Groeneweg, Karen |e investigator |4 oth | |
| 700 | 1 | |a McKinnon, Eileen |e investigator |4 oth | |
| 700 | 1 | |a McRae, Erin |e investigator |4 oth | |
| 700 | 1 | |a Blackie, Kyla |e investigator |4 oth | |
| 700 | 1 | |a Nathoo, Bharat |e investigator |4 oth | |
| 700 | 1 | |a Lau, Kimmy |e investigator |4 oth | |
| 700 | 1 | |a Parmar, Malvinder |e investigator |4 oth | |
| 700 | 1 | |a Gelinas, Sylvie |e investigator |4 oth | |
| 700 | 1 | |a Leblanc, Martine |e investigator |4 oth | |
| 700 | 1 | |a Lépine, Lucie |e investigator |4 oth | |
| 700 | 1 | |a Rigatto, Claudio |e investigator |4 oth | |
| 700 | 1 | |a Friesen, Dolores |e investigator |4 oth | |
| 700 | 1 | |a Soroka, Steven |e investigator |4 oth | |
| 700 | 1 | |a Fleet, Susan |e investigator |4 oth | |
| 700 | 1 | |a Squires, Jeanette |e investigator |4 oth | |
| 700 | 1 | |a Thanamayooran, Siva |e investigator |4 oth | |
| 700 | 1 | |a Binder, Michael |e investigator |4 oth | |
| 700 | 1 | |a Hines, Christine |e investigator |4 oth | |
| 700 | 1 | |a McNeil, Brenda |e investigator |4 oth | |
| 700 | 1 | |a McDougall, Patrice |e investigator |4 oth | |
| 700 | 1 | |a Howard, Joy |e investigator |4 oth | |
| 700 | 1 | |a Gillis, Deborah |e investigator |4 oth | |
| 700 | 1 | |a Hines, Kathleen |e investigator |4 oth | |
| 700 | 1 | |a Tobe, Sheldon |e investigator |4 oth | |
| 700 | 1 | |a Chessman, Mary |e investigator |4 oth | |
| 700 | 1 | |a Perkins, Nancy |e investigator |4 oth | |
| 700 | 1 | |a Agelopoulos, Martha |e investigator |4 oth | |
| 700 | 1 | |a Knox, Stacey |e investigator |4 oth | |
| 700 | 1 | |a Richards, Tiffany |e investigator |4 oth | |
| 700 | 1 | |a Tonelli, Marcello |e investigator |4 oth | |
| 700 | 1 | |a Szigety, Susan |e investigator |4 oth | |
| 700 | 1 | |a Opgenorth, Dawn |e investigator |4 oth | |
| 700 | 1 | |a Yeates, Karen |e investigator |4 oth | |
| 773 | 0 | 8 | |i Enthalten in |t Kidney international |d 1972 |g 89(2016), 5 vom: 13. Mai, Seite 1144-1152 |w (DE-627)NLM000007188 |x 1523-1755 |7 nnns |
| 773 | 1 | 8 | |g volume:89 |g year:2016 |g number:5 |g day:13 |g month:05 |g pages:1144-1152 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.kint.2016.01.014 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 89 |j 2016 |e 5 |b 13 |c 05 |h 1144-1152 | ||