title: Asymmetric dimethylarginine and critical illness.
abstract: OBJECTIVE
  Asymmetric dimethylarginine (ADMA) is an analog of arginine and functions as an endogenous inhibitor of the nitric oxide synthase, which forms nitric oxide. Nitric oxide is crucial for perfusion of vital organs and is an important signaling agent in the development of critical illness. The role of ADMA in the pathophysiological mechanisms underlying critical illness is widely studied in the last decades, and recently it has become clear that ADMA should not be overlooked by clinicians working at the ICU. The aim of this review is to describe new insights into the role of ADMA in critical illness and its clinical relevance.
  
  
  RESULTS
  High levels of ADMA are found in critically ill patients, because of higher levels of protein methylation, increased rate of protein turnover, decreased activity of dimethylamine dimethylaminohydrolase, and impaired renal and hepatic clearance capacity. These high levels are an independent risk factor for cardiac dysfunction, organ failure, and ICU mortality. The arginine : ADMA ratio in particular is of clinical importance and the restoration of this ratio is expedient to restore several functions that are disturbed during critical illness.
  
  
  CONCLUSIONS
  Elevated ADMA levels occur in critically ill patients, which is detrimental for morbidity and mortality. The arginine : ADMA ratio should be restored to maintain nitric oxide production and therewith improve the clinical outcome of the patient.
authors.affiliation: aDepartment of Plastic and Reconstructive Surgery bDepartment of Surgery, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Saskia J H
authors.initials: SJ
authors.lastname: Brinkmann
authors.forename: Myrte C
authors.initials: MC
authors.lastname: de Boer
authors.forename: Nikki
authors.initials: N
authors.lastname: Buijs
authors.forename: Paul A M
authors.initials: PA
authors.lastname: van Leeuwen
mesh_terms: D000581:Amidohydrolases / Q000037:antagonists & inhibitors / Q000378:metabolism; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D016638:Critical Illness / Q000401:mortality*; D004791:Enzyme Inhibitors / Q000097:blood*; D006333:Heart Failure / Q000473:pathology; D006801:Humans; D007362:Intensive Care Units; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D012307:Risk Factors
chemical_list: D004791:Enzyme Inhibitors; D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase; D000581:Amidohydrolases; C059999:dimethylargininase