Citrulline correlations in short bowel syndrome–intestinal failure by patient stratification: Analysis of 24 weeks of teduglutide treatment from a randomized controlled study

Abstract

Background & aims: Disease-associated factors influence parenteral support (PS) reduction in response to teduglutide in patients with intestinal failure associated-short bowel syndrome (SBSeIF). We sought to determine correlative relationships between plasma citrulline levels, small bowel length, and PS volume. Methods: A post hoc analysis of plasma citrulline levels from patients in the STEPS 24-week study of teduglutide in patients with SBSÀIF. Plasma citrulline was assessed in all patients; patients were stratified 3 times into subgroups based on bowel anatomy, cause of SBSeIF, and baseline PS volumes. Correlation analyses used simple linear regression models. Statistical comparisons between study groups were conducted using 2-sided t tests for 2 independent mean differences. Results: Baseline plasma citrulline correlated with remnant small bowel length (r ¼ 0.355, P ¼ 0.002), but not with baseline PS volume (r ¼ À0.167, P ¼ 0.14), in the overall population. There was a robust correlation between the baseline and Week 24 citrulline (r ¼ 0.705, P < 0.0001), and an inverse correlation between change from baseline in citrulline and PS volume from baseline to Week 24 (r ¼ À0.359, P ¼ 0.001). In all subgroups, patients treated with teduglutide showed numerically greater increases in plasma citrulline at Week 24 compared with placebo. Conclusion: Baseline plasma citrulline showed significant correlations with small bowel length in patients with !50% colon remaining/no stoma/colon-in-continuity, and patients with SBSeIF causes other than IBD/vascular disease. Citrulline levels may correlate with PS changes in response to teduglutide and more research may reveal a relationship between citrulline levels within the heterogeneous population of patients with SBSÀIF. ClinicalTrials.gov NCT00798967, ClinicalTrialsRegister.eu 2008-006193-15.

Chronic intestinal failure and short bowel syndrome in Crohn’s disease

“…As a first step, diarrhea is quantified and further characterized by stool frequency, stool weight, and 24-h steatorrhea/creatorrhea[ 25 , 26 ]. The resorptive surface area can be calculated using the D-xylose absorption test and/or serum citrulline[ 27 , 28 ]. However, data published on the validity of serum citrulline determination as a biomarker for bowel length and a prognostic parameter for successful intestinal adaptation are the subject of controversy.…”

Potential Implications of Citrulline and Quercetin on Gut Functioning of Monogastric Animals and Humans: A Comprehensive Review

“…Relatively few studies are available on citrulline in animals; however, it is subtly gaining research interest due to its unique metabolism. Citrulline is a functional marker of gut barrier dysfunction [16], and has been associated with various intestinal diseases, including short bowel syndrome [17,18], gastric ulcers [19], and necrotizing enterocolitis [20]. Recently, flavonoids, a group of natural compounds abundant in plants sources, such as bark, roots, stems, fruits, vegetables, bulbs, wine, and tea, have gained widespread attention for their therapeutic effects such as anti-oxidative, anti-inflammatory, cardioprotective, anti-estrogenic, neuroprotective, and chemoprotective roles [21,22].…”

Citrulline, Biomarker of Enterocyte Functional Mass and Dietary Supplement. Metabolism, Transport, and Current Evidence for Clinical Use

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