title: Asymmetric dimethylarginine, race, and mortality in hemodialysis patients.
abstract: OBJECTIVE
  Levels of asymmetric dimethylarginine, an inhibitor of nitric oxide synthase, are elevated in kidney disease and associated with mortality in white European hemodialysis populations. Nitric oxide production and degradation are partially genetically determined and differ by racial background. No studies have measured asymmetric dimethylarginine in African Americans on dialysis and assessed whether differences exist in its association with mortality by race.
  
  
  METHODS
  Asymmetric dimethylarginine was measured in 259 patients on maintenance hemodialysis assembled from 2004 to 2012 in Boston area outpatient centers. Cox proportional hazards models were used to determine the association between asymmetric dimethylarginine and all-cause mortality, and an interaction with race was tested.
  
  
  RESULTS
  Mean (SD) age was 63 (17) years, 46% were women, and 22% were African American. Mean asymmetric dimethylarginine in non-African Americans was 0.79 µmol/L (0.16) versus 0.70 µmol/L (0.11) in African Americans (P<0.001); 130 patients died over a median follow-up of 2.3 years. African Americans had lower mortality risk than non-African Americans (hazard ratio, 0.27; 95% confidence interval, 0.15 to 0.50) that was robust to adjustment for age, comorbidity, and asymmetric dimethylarginine (hazard ratio, 0.35; 95% confidence interval, 0.17 to 0.69). An interaction was noted between race and asymmetric dimethylarginine (P=0.03), such that asymmetric dimethylarginine was associated with higher mortality in non-African Americans (adjusted hazard ratio, 1.29; 95% confidence interval, 1.06 to 1.57 per 1 SD higher asymmetric dimethylarginine) but not in African Americans (adjusted hazard ratio, 0.57; 95% confidence interval, 0.28 to 1.18). Additional adjustment for fibroblast growth factor 23 partially attenuated the association for non-African Americans (adjusted hazard ratio, 1.22; 95% confidence interval, 0.98 to 1.50).
  
  
  CONCLUSIONS
  African Americans have lower asymmetric dimethylarginine levels and lower hazard for mortality compared with non-African Americans. Levels of asymmetric dimethylarginine did not explain lower hazard for mortality in non-African American patients. High asymmetric dimethylarginine was a risk factor for mortality exclusively in non-African Americans. Mechanisms explaining these relationships need to be evaluated.
authors: Division of Nephrology, Department of Medicine.
authors: David A
authors: DA
authors: Drew
authors: Institute for Clinical Research and Health Policy Studies, and Tufts Clinical and Translational Science Institute, Tufts University, Boston, Massachusetts; and.
authors: Hocine
authors: H
authors: Tighiouart
authors: Department of Psychiatry, Tufts Medical Center, Boston, Massachusetts;
authors: Tammy
authors: T
authors: Scott
authors: Division of Nephrology, Department of Medicine.
authors: Amy
authors: A
authors: Kantor
authors: Division of Nephrology, Department of Medicine.
authors: Li
authors: L
authors: Fan
authors: Department of Laboratory Medicine, University Hospital of Padua, Padua, Italy.
authors: Carlo
authors: C
authors: Artusi
authors: Department of Laboratory Medicine, University Hospital of Padua, Padua, Italy.
authors: Mario
authors: M
authors: Plebani
authors: Division of Nephrology, Department of Medicine.
authors: Daniel E
authors: DE
authors: Weiner
authors: Division of Nephrology, Department of Medicine, msarnak@tuftsmedicalcenter.org.
authors: Mark J
authors: MJ
authors: Sarnak
mesh_terms: D001741:Black or African American; D000368:Aged; D000369:Aged, 80 and over; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001900:Boston / Q000453:epidemiology; D002423:Cause of Death; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000208:ethnology / Q000401:mortality / Q000628:therapy*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D006435:Renal Dialysis / Q000009:adverse effects / Q000401:mortality*; D012307:Risk Factors; D013997:Time Factors
chemical_list: D015415:Biomarkers; C018524:N,N-dimethylarginine; D001120:Arginine
keywords: hemodialysis; mortality risk; nitric oxide