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.

Teduglutide, a novel glucagon-like peptide 2 analog, in the treatment of patients with short bowel syndrome

“…Citrulline is synthesized by enterocytes of intestinal mucosa and is regarded as a biomarker of remnant functional absorptive metabolic mass of enterocytes. A close correlation between citrullinemia and remnant functional small bowel length has been described, but the correlation between citrullinemia and remnant absorptive capacity is less well established [Peters et al 2007;Luo et al 2007]. Thus, future studies should investigate the role of plasma citrulline as a pharmaco-dynamic indicator of the effect of teduglutide.…”

Plasma citrulline as marker of bowel adaptation in children with short bowel syndrome

“…Current clinical practice in weaning short bowel syndrome (SBS) patients from parenteral nutrition (PN) and promoting oral diet is based on clinical data changes, blood test, urine electrolytes output, body weight, and physical examination [1]. Sensitive and reliable clinical markers to predict and to monitor intestinal adaptation are lacking and would be welcome.…”

Insuficiencia intestinal secundaria a síndrome de intestino corto: resultados de un programa multidisciplinario de rehabilitación intestinal

“…En la actualidad, la determinación de niveles plasmáticos de citrulina y la administración de un péptido análogo del glucagón (GLP-2), el primero para estimar la masa de enterocitos remanentes y el segundo para maximizar la capacidad absortiva, son elementos de apoyo en el tratamiento de pacientes con II [28][29][30] . Otro factor en la II es el rol de la inmunidad innata y su relación con determinadas patologías inflamatorias intestinales, su gravedad y alteración en los mecanismos de normal AI.…”