Serum Trimethylamine-N-Oxide Is Strongly Related to Renal Function and Predicts Outcome in Chronic Kidney Disease

The microbial metabolite Trimethylamine-N-oxide (TMAO) has been linked to adverse cardiovascular outcome and mortality in the general population. To assess the contribution of TMAO to inflammation and mortality in chronic kidney disease (CKD) patients ranging from mild-moderate to end-stage disease...

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Vydané v:	PloS one Ročník 11; číslo 1; s. e0141738
Hlavní autori:	Missailidis, Catharina, Hällqvist, Jenny, Qureshi, Abdel Rashid, Barany, Peter, Heimbürger, Olof, Lindholm, Bengt, Stenvinkel, Peter, Bergman, Peter
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States Public Library of Science 2016 Public Library of Science (PLoS)
Predmet:	Adult Aged Atherosclerosis Betaine Betaine - blood Biomarkers Biomarkers - blood C-Reactive Protein - metabolism Cardiovascular disease Cardiovascular diseases Cardiovascular Diseases - blood Cardiovascular Diseases - diagnosis Cardiovascular Diseases - etiology Cardiovascular Diseases - mortality Choline Choline - blood Chromatography Correlation analysis Dialysis Female Fibrinogen Fibrinogen - metabolism Glomerular Filtration Rate Heart failure Hospitals Humans Inflammation Interleukin 6 Interleukin-6 - blood Kidney diseases Kidney Transplantation Kidneys Laboratories Liquid chromatography Longitudinal Studies Male Mass spectrometry Mass spectroscopy Medicine Metabolism Metabolites Methylamines - blood Microbiota Microorganisms Middle Aged Mortality Multivariate Analysis Nephrology Nutrition Nutritional status Patients Peritoneal dialysis Prognosis Renal Dialysis Renal function Renal Insufficiency, Chronic - blood Renal Insufficiency, Chronic - complications Renal Insufficiency, Chronic - diagnosis Renal Insufficiency, Chronic - mortality Science Severity of Illness Index Studies Survival Analysis Transplantation Trimethylamine Trimethylamine-N-oxide Urologi och njurmedicin Urology and Nephrology Sweden
ISSN:	1932-6203, 1932-6203
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Shrnutí:	The microbial metabolite Trimethylamine-N-oxide (TMAO) has been linked to adverse cardiovascular outcome and mortality in the general population. To assess the contribution of TMAO to inflammation and mortality in chronic kidney disease (CKD) patients ranging from mild-moderate to end-stage disease and 1) associations with glomerular filtration rate (GFR) 2) effect of dialysis and renal transplantation (Rtx) 3) association with inflammatory biomarkers and 4) its predictive value for all-cause mortality. Levels of metabolites were quantified by a novel liquid chromatography/tandem mass spectrometry-based method in fasting plasma samples from 80 controls and 179 CKD 3-5 patients. Comorbidities, nutritional status, biomarkers of inflammation and GFR were assessed. GFR was the dominant variable affecting TMAO (β = -0.41; p<0.001), choline (β = -0.38; p<0.001), and betaine (β = 0.45; p<0.001) levels. A longitudinal study of 74 CKD 5 patients starting renal replacement therapy demonstrated that whereas dialysis treatment did not affect TMAO, Rtx reduced levels of TMAO to that of controls (p<0.001). Following Rtx choline and betaine levels continued to increase. In CKD 3-5, TMAO levels were associated with IL-6 (Rho = 0.42; p<0.0001), fibrinogen (Rho = 0.43; p<0.0001) and hsCRP (Rho = 0.17; p = 0.022). Higher TMAO levels were associated with an increased risk for all-cause mortality that remained significant after multivariate adjustment (HR 4.32, 95% CI 1.32-14.2; p = 0.016). Elevated TMAO levels are strongly associated with degree of renal function in CKD and normalize after renal transplantation. TMAO levels correlates with increased systemic inflammation and is an independent predictor of mortality in CKD 3-5 patients.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Competing Interests: The authors have declared that no competing interests exist. Conceived and designed the experiments: CM JH PS PB. Performed the experiments: CM JH PB. Analyzed the data: CM JH ARQ PB. Contributed reagents/materials/analysis tools: CM JH ARQ PB OH BL PS PB. Wrote the paper: CM JH ARQ PB OH BL PS PB.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0141738