title: Are plasma citrulline and glutamine biomarkers of intestinal absorptive function in patients with short bowel syndrome?
abstract: Sensitive biomarkers for intestinal absorptive function would be clinically useful in short bowel syndrome (SBS). Citrulline (Cit) is a product of the metabolism of glutamine (Gln) and derived amino acids by enterocytes. Cit is produced almost exclusively by the gut, which is also a major site of Gln metabolism. The goals of this study were to examine whether plasma Cit and Gln concentrations are biomarkers of residual small intestinal length and nutrient absorptive functions in adult SBS patients followed prospectively. We studied 24 stable adults with severe SBS receiving chronic parenteral nutrition (PN) in a double-blind, randomized trial of individualized dietary modification +/- recombinant human growth hormone (GH). During a baseline week, intestinal absorption studies (% absorption of fluid, kcal, nitrogen, fat, carbohydrate, sodium, phosphorus, and magnesium) were performed and concomitant plasma Cit and Gln concentrations determined. Individualized dietary modification and treatment with subcutaneous injection of placebo (n = 9) or GH (0.1 mg/kg daily x 21 days, then 3 times/week; n = 15) were then begun. PN weaning was initiated after week 4 and continued as tolerated for 24 weeks. Repeat plasma amino acid determination and nutrient absorption studies were performed at weeks 4 and 12. Residual small bowel length at baseline was positively correlated with baseline plasma Cit (r = 0.467; p = .028). However, no significant correlations between absolute Cit or Gln concentrations and the percent absorption of nutrient substrates at any time point were observed. Similarly, no correlation between the change in Cit or GLN concentration and the change in % nutrient absorption was observed (baseline vs weeks 4 and 12, respectively). By weeks 12 and 24, 7 and 13 subjects were weaned completely from PN, respectively. However, baseline plasma Cit or Gln did not predict PN weaning at these time points. We concluded that plasma Cit (but not Gln) concentrations appeared to be an indicator of small intestinal length in adult SBS. However, neither plasma Cit nor Gln was a biomarker for intestinal absorptive function in this cohort of patients with SBS.
authors.affiliation: Department of Medicine, Emory Center for Clinical and Molecular Nutrition, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: Menghua
authors.initials: M
authors.lastname: Luo
authors.forename: Concepción
authors.initials: C
authors.lastname: Fernández-Estívariz
authors.forename: Amita K
authors.initials: AK
authors.lastname: Manatunga
authors.forename: Niloofar
authors.initials: N
authors.lastname: Bazargan
authors.forename: Li H
authors.initials: LH
authors.lastname: Gu
authors.forename: Dean P
authors.initials: DP
authors.lastname: Jones
authors.forename: Jan-Michael
authors.initials: JM
authors.lastname: Klapproth
authors.forename: Shanthi V
authors.initials: SV
authors.lastname: Sitaraman
authors.forename: Lorraine M
authors.initials: LM
authors.lastname: Leader
authors.forename: John R
authors.initials: JR
authors.lastname: Galloway
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Ziegler
mesh_terms: D015415:Biomarkers / Q000097:blood; D002956:Citrulline / Q000493:pharmacokinetics*; D004311:Double-Blind Method; D005260:Female; D005973:Glutamine / Q000493:pharmacokinetics*; D019382:Human Growth Hormone / Q000008:administration & dosage; D006801:Humans; D007408:Intestinal Absorption / Q000502:physiology*; D007421:Intestine, Small / Q000033:anatomy & histology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010288:Parenteral Nutrition; D011446:Prospective Studies; D012778:Short Bowel Syndrome / Q000097:blood / Q000378:metabolism* / Q000628:therapy
chemical_list: D015415:Biomarkers; D005973:Glutamine; D019382:Human Growth Hormone; D002956:Citrulline