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Observational Study
. 2016 May;89(5):1144-1152.
doi: 10.1016/j.kint.2016.01.014. Epub 2016 Mar 19.

Advanced chronic kidney disease populations have elevated trimethylamine N-oxide levels associated with increased cardiovascular events

Richard B Kim  1 , Bridget L Morse  2 , Ognjenka Djurdjev  3 , Mila Tang  3 , Norman Muirhead  2 , Brendan Barrett  4 , Daniel T Holmes  5 , Francois Madore  6 , Catherine M Clase  7 , Claudio Rigatto  8 , Adeera Levin  9 ; CanPREDDICT Investigators
Collaborators, Affiliations
Free article
Observational Study

Advanced chronic kidney disease populations have elevated trimethylamine N-oxide levels associated with increased cardiovascular events

Richard B Kim et al. Kidney Int. 2016 May.
Free article

Abstract

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.

Keywords: cardiovascular risk; chronic kidney disease; trimethylamine N-oxide.

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