title: Serum Asymmetric and Symmetric Dimethylarginine and Morbidity and Mortality in Hemodialysis Patients.
abstract: BACKGROUND
  Asymmetric (ADMA) and symmetric dimethylarginine (SDMA) are putative uremic toxins that may exert toxicity by a number of mechanisms, including impaired nitric oxide synthesis and generation of reactive oxygen species. The study goal was to determine the association between these metabolites and cardiovascular outcomes in hemodialysis patients.
  
  
  METHODS
  Post hoc analysis of the Hemodialysis (HEMO) Study.
  
  
  METHODS
  1,276 prevalent hemodialysis patients with available samples 3 to 6 months after randomization.
  
  
  METHODS
  ADMA and SDMA measured in stored specimens.
  
  
  RESULTS
  Cardiac death, sudden cardiac death, first cardiovascular event, and any-cause death. Association with predictors analyzed using Cox regression adjusted for potential confounders (including demographics, clinical characteristics, comorbid conditions, albumin level, and residual kidney function).
  
  
  RESULTS
  Mean age of patients was 57±14 (SD) years, 63% were black, and 57% were women. Mean ADMA (0.9±0.2μmol/L) and SDMA levels (4.3±1.4μmol/L) were moderately correlated (r=0.418). Higher dialysis dose or longer session length were not associated with lower predialysis ADMA or SDMA concentrations. In fully adjusted models, each doubling of ADMA level was associated with higher risk (HR per 2-fold higher concentration; 95% CI) of cardiac death (1.83; 1.29-2.58), sudden cardiac death (1.79; 1.19-2.69), first cardiovascular event (1.50; 1.20-1.87), and any-cause death (1.44; 1.13-1.83). Compared to the lowest ADMA quintile (<0.745 μmol/L), the highest ADMA quintile (≥1.07μmol/L) was associated with higher risk (HR; 95% CI) of cardiac death (2.10; 1.44-3.05), sudden cardiac death (2.06; 1.46-2.90), first cardiovascular event (1.75; 1.35-2.27), and any-cause death (1.56; 1.21-2.00). SDMA level was associated with higher risk for cardiac death (HR, 1.40; 95% CI, 1.03-1.92), but this was no longer statistically significant after adjusting for ADMA level (HR, 1.20; 95% CI, 0.86-1.68).
  
  
  CONCLUSIONS
  Single time-point measurement of ADMA and SDMA.
  
  
  CONCLUSIONS
  ADMA and, to a lesser extent, SDMA levels are associated with cardiovascular outcomes in hemodialysis patients.
authors.affiliation: Department of Medicine, Johns Hopkins University, Baltimore, MD; Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, Baltimore, MD. Electronic address: tshafi@jhmi.edu.
authors.forename: Tariq
authors.initials: T
authors.lastname: Shafi
authors.affiliation: Department of Medicine, Case Western University School of Medicine, Cleveland, OH.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Hostetter
authors.affiliation: Department of Medicine, Palo Alto Veterans Affairs Health Care System and Stanford University, Palo Alto, CA.
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Meyer
authors.affiliation: Department of Medicine, Johns Hopkins University, Baltimore, MD.
authors.forename: Seungyoung
authors.initials: S
authors.lastname: Hwang
authors.affiliation: Department of Medicine, Case Western University School of Medicine, Cleveland, OH.
authors.forename: Xin
authors.initials: X
authors.lastname: Hai
authors.affiliation: Department of Medicine, Albert Einstein College of Medicine, Bronx, NY; Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY.
authors.forename: Michal L
authors.initials: ML
authors.lastname: Melamed
authors.affiliation: Department of Medicine, University of California, San Francisco, CA.
authors.forename: Tanushree
authors.initials: T
authors.lastname: Banerjee
authors.affiliation: Department of Medicine, Johns Hopkins University, Baltimore, MD; Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, Baltimore, MD; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
authors.forename: Josef
authors.initials: J
authors.lastname: Coresh
authors.affiliation: Department of Medicine, University of California, San Francisco, CA.
authors.forename: Neil R
authors.initials: NR
authors.lastname: Powe
mesh_terms: D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood* / Q000453:epidemiology* / Q000401:mortality; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009017:Morbidity; D011446:Prospective Studies; D006435:Renal Dialysis
chemical_list: C024917:symmetric dimethylarginine; C018524:N,N-dimethylarginine; D001120:Arginine
keywords: Cardiovascular mortality; asymmetric dimethylarginine (ADMA); cardiac death; cardiovascular morbidity; dialysis outcomes; end-stage renal disease (ESRD); hemodialysis; sudden cardiac death; symmetric dimethylarginine (SDMA); uremic toxins