title: Associations of Trimethylamine N-Oxide With Nutritional and Inflammatory Biomarkers and Cardiovascular Outcomes in Patients New to Dialysis.
abstract: OBJECTIVE
  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, 43 μM/L; 25th-75th percentile, 28-67 μM/L) were elevated compared with those with normal or near-normal kidney function (1.41 ± 0.49 μM/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.
authors: Department of Medicine, University of California, Davis, Davis, California; Department of Biochemistry and Molecular Medicine, University of California, Davis, Davis California. Electronic address: gakaysen@ucdavis.edu.
authors: George A
authors: GA
authors: Kaysen
authors: San Francisco Department of Veterans Affairs Medical Center, San Francisco, California; Department of Medicine, University of California, San Francisco, San Francisco, California.
authors: Kirsten L
authors: KL
authors: Johansen
authors: Department of Medicine, Stanford University School of Medicine, Palo Alto, California.
authors: Glenn M
authors: GM
authors: Chertow
authors: Department of Medicine, University of California, Davis, Davis, California.
authors: Lorien S
authors: LS
authors: Dalrymple
authors: Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California.
authors: John
authors: J
authors: Kornak
authors: Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California.
authors: Barbara
authors: B
authors: Grimes
authors: Department of Medicine, University of California, Davis, Davis, California.
authors: Tjien
authors: T
authors: Dwyer
authors: Department of Molecular and Cellular Biology and Genome Center University of California, Davis, Davis California.
authors: Alexander W
authors: AW
authors: Chassy
authors: Department of Molecular and Cellular Biology and Genome Center University of California, Davis, Davis California.
authors: Oliver
authors: O
authors: Fiehn
mesh_terms: D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein; D002318:Cardiovascular Diseases / Q000097:blood / Q000401:mortality*; D002853:Chromatography, Liquid; D015331:Cohort Studies; D015897:Comorbidity; D005260:Female; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D007249:Inflammation / Q000097:blood*; D053208:Kaplan-Meier Estimate; D007676:Kidney Failure, Chronic / Q000097:blood / Q000401:mortality / Q000628:therapy*; D008297:Male; D008744:Methylamines / Q000097:blood*; D008875:Middle Aged; D009752:Nutritional Status; D006435:Renal Dialysis; D012307:Risk Factors; D053719:Tandem Mass Spectrometry
chemical_list: D015415:Biomarkers; D008744:Methylamines; D002097:C-Reactive Protein; C005855:trimethyloxamine