title: Citrulline as a biomarker of intestinal failure due to enterocyte mass reduction.
abstract: OBJECTIVE
  In human, citrulline (plasma concentration about 40 micromol/L) is an amino acid involved in intermediary metabolism and that is not incorporated in proteins. Circulating citrulline is mainly produced by enterocytes of the small bowel. For this reason plasma or serum citrulline concentration has been proposed as a biomarker of remnant small bowel mass and function. This article reviews this concept and its metabolic basis.
  
  
  METHODS
  Conditions in which there is a significantly reduced small bowel enterocyte mass and function and a plasma or serum citrulline were measured in adults and children. These studies included patients with a short bowel syndrome, villous atrophy states, Crohn's disease, during monitoring of digestive toxicity of chemotherapy and radiotherapy or follow-up of patients after small bowel transplantation.
  
  
  RESULTS
  In all these situations, with more than 500 studied patients a decreased level of plasma citrulline correlated with the reduced enterocyte mass independently of nutritional and inflammatory status. A close correlation between small bowel remnant length and citrullinemia was found. In addition, diagnosis of intestinal failure was assessed through plasma citrulline levels in severe small bowel diseases in which there is a marked enterocyte mass reduction.
  
  
  CONCLUSIONS
  The threshold for establishing a diagnosis of intestinal failure is lower in villous atrophy disease (10mumol/L) than in short bowel syndrome (20mumol/L). Compromised renal function is an important factor when considering plasma citrulline levels as a marker of intestinal failure as this potentially can increase circulating citrulline values.
  
  
  CONCLUSIONS
  Reduced plasma citrulline levels are an innovative quantitative biomarker of significantly reduced enterocyte mass and function in different disease states in humans.
authors.affiliation: Département de Médecine, Hôpital Raymond Poincaré, Assistance Publique-Hôpitaux de Paris, Université de Versailles Saint-Quentin-en-Yvelines, Garches, France. pascal.crenn@rpc.aphp.fr
authors.forename: Pascal
authors.initials: P
authors.lastname: Crenn
authors.forename: Bernard
authors.initials: B
authors.lastname: Messing
authors.forename: Luc
authors.initials: L
authors.lastname: Cynober
mesh_terms: D015415:Biomarkers; D002956:Citrulline / Q000032:analysis / Q000097:blood*; D020895:Enterocytes / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007421:Intestine, Small / Q000166:cytology / Q000378:metabolism / Q000473:pathology* / Q000502:physiology*; D011237:Predictive Value of Tests; D012778:Short Bowel Syndrome / Q000097:blood* / Q000175:diagnosis / Q000473:pathology
chemical_list: D015415:Biomarkers; D002956:Citrulline