Associations of Trimethylamine N-Oxide With Nutritional and Inflammatory Biomarkers and Cardiovascular Outcomes in Patients New to Dialysis

George Kaysen, Kirsten L. Johansen, Glenn M. Chertow, Lorien Dalrymple, John Kornak, Barbara Grimes, Tjien Dwyer, Alexander W. Chassy, Oliver Fiehn

Research output: Contribution to journalArticle

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Abstract

Objectives: Trimethylamine N-oxide (TMAO) is a product of metabolism of phosphatidylcholine (lecithin) and carnitine by the intestinal microbiome. Elevated serum concentrations of TMAO have been linked to adverse cardiovascular outcomes in the general population. We examined correlates of serum TMAO and the relations among serum TMAO concentrations, all-cause mortality, and cardiovascular mortality and hospitalizations in a nationally derived cohort of patients new to hemodialysis (HD). Methods: We quantified serum TMAO by liquid chromatography and online tandem mass spectrometry and assessed nutritional and cardiovascular risk factors in 235 patients receiving HD and measured TMAO in pooled serum from healthy controls. We analyzed time to death and time to cardiovascular death or hospitalization using Cox proportional hazards regression. Results: Serum TMAO concentrations of patients undergoing HD (median, 43μM/L; 25th-75th percentile, 28-67μM/L) were elevated compared with those with normal or near-normal kidney function (1.41±0.49μM/L). TMAO was directly correlated with serum albumin (Spearman rank correlation, 0.24; 95% CI, 0.12-0.35; P <.001), prealbumin (Spearman rank correlation, 0.19; 95% CI, 0.07-0.31; P=.003), and creatinine (Spearman rank correlation, 0.21; 95% CI, 0.08-0.33; P=.002) and inversely correlated with log C-reactive protein (Spearman rank correlation, -0.18; 95% CI, -0.30 to -0.06; P=.005). Higher serum concentrations of TMAO were not significantly associated with time to death (Spearman rank correlation, 0.84; CI, 0.65-1.09; P=.19) or time to cardiovascular hospitalization or cardiovascular death (Spearman rank correlation, 0.88; CI, 0.57-1.35; P=.55). Conclusions: Serum TMAO concentrations were markedly elevated and correlated directly with biochemical markers of nutritional status and inversely with markers of inflammation in patients receiving HD. There was no significant association between serum TMAO concentrations and all-cause mortality, cardiovascular death, or hospitalizations. In patients receiving dialysis-in contrast with the general population-adverse vascular effects of TMAO may be counterbalanced by associations with nutritional or inflammatory status.

Original languageEnglish (US)
Pages (from-to)351-356
Number of pages6
JournalJournal of Renal Nutrition
Volume25
Issue number4
DOIs
StatePublished - Jul 1 2015

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Dialysis
Biomarkers
Serum
Renal Dialysis
Hospitalization
Mortality
trimethyloxamine
Prealbumin
Lecithins
Carnitine
Tandem Mass Spectrometry
Nutritional Status
Phosphatidylcholines
Serum Albumin
Liquid Chromatography
C-Reactive Protein
Population
Blood Vessels
Creatinine
Inflammation

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics
  • Nephrology

Cite this

Associations of Trimethylamine N-Oxide With Nutritional and Inflammatory Biomarkers and Cardiovascular Outcomes in Patients New to Dialysis. / Kaysen, George; Johansen, Kirsten L.; Chertow, Glenn M.; Dalrymple, Lorien; Kornak, John; Grimes, Barbara; Dwyer, Tjien; Chassy, Alexander W.; Fiehn, Oliver.

In: Journal of Renal Nutrition, Vol. 25, No. 4, 01.07.2015, p. 351-356.

Research output: Contribution to journalArticle

Kaysen, George ; Johansen, Kirsten L. ; Chertow, Glenn M. ; Dalrymple, Lorien ; Kornak, John ; Grimes, Barbara ; Dwyer, Tjien ; Chassy, Alexander W. ; Fiehn, Oliver. / Associations of Trimethylamine N-Oxide With Nutritional and Inflammatory Biomarkers and Cardiovascular Outcomes in Patients New to Dialysis. In: Journal of Renal Nutrition. 2015 ; Vol. 25, No. 4. pp. 351-356.
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abstract = "Objectives: Trimethylamine N-oxide (TMAO) is a product of metabolism of phosphatidylcholine (lecithin) and carnitine by the intestinal microbiome. Elevated serum concentrations of TMAO have been linked to adverse cardiovascular outcomes in the general population. We examined correlates of serum TMAO and the relations among serum TMAO concentrations, all-cause mortality, and cardiovascular mortality and hospitalizations in a nationally derived cohort of patients new to hemodialysis (HD). Methods: We quantified serum TMAO by liquid chromatography and online tandem mass spectrometry and assessed nutritional and cardiovascular risk factors in 235 patients receiving HD and measured TMAO in pooled serum from healthy controls. We analyzed time to death and time to cardiovascular death or hospitalization using Cox proportional hazards regression. Results: Serum TMAO concentrations of patients undergoing HD (median, 43μM/L; 25th-75th percentile, 28-67μM/L) were elevated compared with those with normal or near-normal kidney function (1.41±0.49μM/L). TMAO was directly correlated with serum albumin (Spearman rank correlation, 0.24; 95{\%} CI, 0.12-0.35; P <.001), prealbumin (Spearman rank correlation, 0.19; 95{\%} CI, 0.07-0.31; P=.003), and creatinine (Spearman rank correlation, 0.21; 95{\%} CI, 0.08-0.33; P=.002) and inversely correlated with log C-reactive protein (Spearman rank correlation, -0.18; 95{\%} CI, -0.30 to -0.06; P=.005). Higher serum concentrations of TMAO were not significantly associated with time to death (Spearman rank correlation, 0.84; CI, 0.65-1.09; P=.19) or time to cardiovascular hospitalization or cardiovascular death (Spearman rank correlation, 0.88; CI, 0.57-1.35; P=.55). Conclusions: Serum TMAO concentrations were markedly elevated and correlated directly with biochemical markers of nutritional status and inversely with markers of inflammation in patients receiving HD. There was no significant association between serum TMAO concentrations and all-cause mortality, cardiovascular death, or hospitalizations. In patients receiving dialysis-in contrast with the general population-adverse vascular effects of TMAO may be counterbalanced by associations with nutritional or inflammatory status.",
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AU - Kaysen, George

AU - Johansen, Kirsten L.

AU - Chertow, Glenn M.

AU - Dalrymple, Lorien

AU - Kornak, John

AU - Grimes, Barbara

AU - Dwyer, Tjien

AU - Chassy, Alexander W.

AU - Fiehn, Oliver

PY - 2015/7/1

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N2 - Objectives: Trimethylamine N-oxide (TMAO) is a product of metabolism of phosphatidylcholine (lecithin) and carnitine by the intestinal microbiome. Elevated serum concentrations of TMAO have been linked to adverse cardiovascular outcomes in the general population. We examined correlates of serum TMAO and the relations among serum TMAO concentrations, all-cause mortality, and cardiovascular mortality and hospitalizations in a nationally derived cohort of patients new to hemodialysis (HD). Methods: We quantified serum TMAO by liquid chromatography and online tandem mass spectrometry and assessed nutritional and cardiovascular risk factors in 235 patients receiving HD and measured TMAO in pooled serum from healthy controls. We analyzed time to death and time to cardiovascular death or hospitalization using Cox proportional hazards regression. Results: Serum TMAO concentrations of patients undergoing HD (median, 43μM/L; 25th-75th percentile, 28-67μM/L) were elevated compared with those with normal or near-normal kidney function (1.41±0.49μM/L). TMAO was directly correlated with serum albumin (Spearman rank correlation, 0.24; 95% CI, 0.12-0.35; P <.001), prealbumin (Spearman rank correlation, 0.19; 95% CI, 0.07-0.31; P=.003), and creatinine (Spearman rank correlation, 0.21; 95% CI, 0.08-0.33; P=.002) and inversely correlated with log C-reactive protein (Spearman rank correlation, -0.18; 95% CI, -0.30 to -0.06; P=.005). Higher serum concentrations of TMAO were not significantly associated with time to death (Spearman rank correlation, 0.84; CI, 0.65-1.09; P=.19) or time to cardiovascular hospitalization or cardiovascular death (Spearman rank correlation, 0.88; CI, 0.57-1.35; P=.55). Conclusions: Serum TMAO concentrations were markedly elevated and correlated directly with biochemical markers of nutritional status and inversely with markers of inflammation in patients receiving HD. There was no significant association between serum TMAO concentrations and all-cause mortality, cardiovascular death, or hospitalizations. In patients receiving dialysis-in contrast with the general population-adverse vascular effects of TMAO may be counterbalanced by associations with nutritional or inflammatory status.

AB - Objectives: Trimethylamine N-oxide (TMAO) is a product of metabolism of phosphatidylcholine (lecithin) and carnitine by the intestinal microbiome. Elevated serum concentrations of TMAO have been linked to adverse cardiovascular outcomes in the general population. We examined correlates of serum TMAO and the relations among serum TMAO concentrations, all-cause mortality, and cardiovascular mortality and hospitalizations in a nationally derived cohort of patients new to hemodialysis (HD). Methods: We quantified serum TMAO by liquid chromatography and online tandem mass spectrometry and assessed nutritional and cardiovascular risk factors in 235 patients receiving HD and measured TMAO in pooled serum from healthy controls. We analyzed time to death and time to cardiovascular death or hospitalization using Cox proportional hazards regression. Results: Serum TMAO concentrations of patients undergoing HD (median, 43μM/L; 25th-75th percentile, 28-67μM/L) were elevated compared with those with normal or near-normal kidney function (1.41±0.49μM/L). TMAO was directly correlated with serum albumin (Spearman rank correlation, 0.24; 95% CI, 0.12-0.35; P <.001), prealbumin (Spearman rank correlation, 0.19; 95% CI, 0.07-0.31; P=.003), and creatinine (Spearman rank correlation, 0.21; 95% CI, 0.08-0.33; P=.002) and inversely correlated with log C-reactive protein (Spearman rank correlation, -0.18; 95% CI, -0.30 to -0.06; P=.005). Higher serum concentrations of TMAO were not significantly associated with time to death (Spearman rank correlation, 0.84; CI, 0.65-1.09; P=.19) or time to cardiovascular hospitalization or cardiovascular death (Spearman rank correlation, 0.88; CI, 0.57-1.35; P=.55). Conclusions: Serum TMAO concentrations were markedly elevated and correlated directly with biochemical markers of nutritional status and inversely with markers of inflammation in patients receiving HD. There was no significant association between serum TMAO concentrations and all-cause mortality, cardiovascular death, or hospitalizations. In patients receiving dialysis-in contrast with the general population-adverse vascular effects of TMAO may be counterbalanced by associations with nutritional or inflammatory status.

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