title: Serum citrulline as a biomarker of gastrointestinal function during hematopoietic cell transplantation in children.
abstract: OBJECTIVE
  We sought to determine whether serum citrulline (CIT), an amino acid produced by small bowel enterocytes, was associated with clinical and biochemical markers of gastrointestinal function in children undergoing hematopoietic cell transplantation (HCT).
  
  
  METHODS
  We conducted a multicenter, prospective cohort study of 26 children to define time-related changes in serum CIT during the course of HCT. Markers of gastrointestinal function including oral energy intake, emesis, stool volume, presence of graft-versus-host disease (GVHD), oral mucositis severity, and cytokine and neurohormone levels were measured. Weekly serum CIT concentrations were obtained from 10 days prior until 30 days after HCT.
  
  
  RESULTS
  Mean baseline CIT concentration was 22.7 μmol/L (95% confidence interval [CI] 17.7-27.6) on day -10, which decreased to a nadir of 7.5 μmol/L (95% CI 3.1-18.0, P = 0.017) on day 8 following HCT before returning to baseline by day 30. After adjustment for IL-6 level (1.0% lower CIT per 10% increase in interleukin-6, P = 0.004), presence of acute GVHD (27% lower CIT, P = 0.025), and oral energy intake (2.1% lower CIT per 10% decrease in energy intake, P = 0.018), the nadir shifted to day 10, when mean CIT concentration was lower in patients with severe oral mucositis (6.7 μmol/L, 95% CI 3.4-13.1) than in those without severe mucositis (11.9 μmol/L, 95% CI 5.8-24.4, P = 0.003). Change in CIT was not correlated with stool volume, C-reactive protein, tumor necrosis factor-α, leptin, or ghrelin.
  
  
  CONCLUSIONS
  In children undergoing HCT, serum CIT correlates with measures of gastrointestinal function (oral mucositis severity, dietary intake, acute GVHD) and may reflect mucosal injury to the gastrointestinal tract.
authors.affiliation: *Boston Children's Hospital, Boston, MA †UCLA Mattel Children's Hospital, Los Angeles, CA ‡Brown University, Providence, RI §Dana-Farber Cancer Institute, Boston, MA.
authors.forename: Kerri B
authors.initials: KB
authors.lastname: Gosselin
authors.forename: Henry A
authors.initials: HA
authors.lastname: Feldman
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Sonis
authors.forename: Lori J
authors.initials: LJ
authors.lastname: Bechard
authors.forename: Mark D
authors.initials: MD
authors.lastname: Kellogg
authors.forename: Kathleen
authors.initials: K
authors.lastname: Gura
authors.forename: Robert
authors.initials: R
authors.lastname: Venick
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Gordon
authors.forename: Eva C
authors.initials: EC
authors.lastname: Guinan
authors.forename: Christopher
authors.initials: C
authors.lastname: Duggan
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000097:blood; D002648:Child; D002956:Citrulline / Q000097:blood*; D002149:Energy Intake; D006086:Graft vs Host Disease / Q000097:blood* / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D009061:Mouth Mucosa / Q000473:pathology*; D052016:Mucositis / Q000097:blood* / Q000209:etiology; D011446:Prospective Studies
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; D002956:Citrulline