title: Admission levels of asymmetric and symmetric dimethylarginine predict long-term outcome in patients with community-acquired pneumonia.
abstract: During infection, there is an activation of the L-arginine-nitric-oxide pathway, with a shift from nitric oxide synthesis to a degradation of L-arginine to its metabolites, asymmetric and symmetric dimethylarginine (ADMA and SDMA). However, the prognostic implications for short-term or long-term survival remains unclear. We investigated the association of L-arginine, ADMA, and SDMA with adverse clinical outcomes in a well-defined cohort of patients with community-acquired pneumonia (CAP).
  
  
  
  We measured L-arginine, ADMA, and SDMA in 268 CAP patients from a Swiss multicenter trial by mass spectrometry and used Cox regression models to investigate associations between blood marker levels and disease severity as well as mortality over a period of 6 years.
  
  
  
  Six-year mortality was 44.8%. Admission levels of ADMA and SDMA (μmol/L) were correlated with CAP severity as assessed by the pneumonia severity index (r = 0.32, p < 0.001 and r = 0.56, p < 0.001 for ADMA and SDMA, respectively) and higher in 6-year non-survivors versus survivors (median 0.62 vs. 0.48; p < 0.001 and 1.01 vs. 0.85; p < 0.001 for ADMA and SDMA, respectively). Both ADMA and SDMA were significantly associated with long-term mortality (hazard ratios [HR] 4.44 [95% confidence intervals (CI) 1.84 to 10.74] and 2.81 [95% CI 1.45 to 5.48], respectively). The effects were no longer significant after multivariate adjustment for age and comorbidities. No association of L-arginine with severity and outcome was found.
  
  
  
  Both ADMA and SDMA show a severity-dependent increase in patients with CAP and are strongly associated with mortality. This association is mainly explained by age and comorbidities.
  
  
  
  ISRCTN95122877 . Registered 31 July 2006.
authors.affiliation: Kantonsspital Aarau, University Department of Internal Medicine, Tellstrasse, CH-5001, Aarau, Switzerland.
authors.forename: Alaadin
authors.initials: A
authors.lastname: Vögeli
authors.affiliation: Kantonsspital Aarau, University Department of Internal Medicine, Tellstrasse, CH-5001, Aarau, Switzerland.
authors.forename: Manuel
authors.initials: M
authors.lastname: Ottiger
authors.affiliation: Kantonsspital Aarau, University Department of Internal Medicine, Tellstrasse, CH-5001, Aarau, Switzerland.
authors.forename: Marc A
authors.initials: MA
authors.lastname: Meier
authors.affiliation: Institute of Laboratory Medicine, Kantonsspital Aarau, Aarau, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Steuer
authors.affiliation: Institute of Laboratory Medicine, Kantonsspital Aarau, Aarau, Switzerland.
authors.forename: Luca
authors.initials: L
authors.lastname: Bernasconi
authors.affiliation: Asclepius Medical Communications LLC, Ridgewood, NJ, USA.
authors.forename: Prasad
authors.initials: P
authors.lastname: Kulkarni
authors.affiliation: Institute of Laboratory Medicine, Kantonsspital Aarau, Aarau, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Huber
authors.affiliation: Endocrinology, Diabetology, and Metabolism, University Hospital Basel, Basel, Switzerland.
authors.forename: Mirjam
authors.initials: M
authors.lastname: Christ-Crain
authors.affiliation: Department of Internal Medicine, Kantonsspital Luzern, Luzern, Switzerland.
authors.forename: Christoph
authors.initials: C
authors.lastname: Henzen
authors.affiliation: Department of Internal Medicine, Kantonsspital Münsterlingen, Münsterlingen, Switzerland.
authors.forename: Claus
authors.initials: C
authors.lastname: Hoess
authors.affiliation: Department of Internal Medicine, Bürgerspital Solothurn, Solothurn, Switzerland.
authors.forename: Robert
authors.initials: R
authors.lastname: Thomann
authors.affiliation: Kantonsspital Baselland, University Department of Internal Medicine, Liestal, Switzerland.
authors.forename: Werner
authors.initials: W
authors.lastname: Zimmerli
authors.affiliation: Kantonsspital Aarau, University Department of Internal Medicine, Tellstrasse, CH-5001, Aarau, Switzerland.
authors.forename: Beat
authors.initials: B
authors.lastname: Mueller
authors.affiliation: Kantonsspital Aarau, University Department of Internal Medicine, Tellstrasse, CH-5001, Aarau, Switzerland. schuetzph@gmail.com.
authors.forename: Philipp
authors.initials: P
authors.lastname: Schuetz
mesh_terms: D000328:Adult; D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D017714:Community-Acquired Infections / Q000097:blood* / Q000175:diagnosis / Q000401:mortality*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010343:Patient Admission / Q000706:statistics & numerical data; D011014:Pneumonia / Q000097:blood* / Q000175:diagnosis / Q000401:mortality*; D015995:Prevalence; D016016:Proportional Hazards Models; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors; D016019:Survival Analysis; D013557:Switzerland / Q000453:epidemiology
chemical_list: D015415:Biomarkers; C024917:symmetric dimethylarginine; C018524:N,N-dimethylarginine; D001120:Arginine
keywords: Asymmetric dimethylarginine (ADMA); Biomarker; Community-acquired pneumonia (CAP); L-arginine; Mortality prediction; Symmetric dimethylarginine (SDMA)