Postabsorptive plasma citrulline concentration is a marker of absorptive enterocyte mass and intestinal failure in humans

Background & Aims: No blood marker assessing the functional absorptive bowe l length has been identified. Plasma citrulline, a nonprotein amino acid pr oduced by intestinal mucosa, is one candidate. We tested this hypothesis in adult patients with the shortbowel syndrome, whose condition can lead to i ntestinal failure. Methods: In 57 patients, after a minimal follow-up of 2 years subsequent to final digestive circuit modification, postabsorptive ci trulline concentration was measured and parenteral nutrition dependence was used to define permanent (n = 37) and transient (n = 20) intestinal failur e. Absorptive function, studied over a 3-day period, was evaluated by net d igestive absorption for protein and fat (n = 51). Relations between quantit ative values were assessed by linear regression analysis and cutoff citrull ine threshold, for a diagnosis of intestinal failure by linear discriminant analysis. Cox model was used to compare citrulline threshold and anatomic variables of the short bowel as indicators of transient as opposed to perma nent intestinal failure. Results: In patients with short-bowel syndrome, ci trulline levels were lower than in controls (n = 51): 20 +/- 13 vs. 40 +/- 10 mu mol/L (mean +/- SD), respectively (P < 0.001). After multivariate ana lysis, citrullinemia was correlated to small bowel length (P < 0.0001, r = 0.86) and to net digestive absorption of fat, but to neither body mass inde x nor creatinine clearance. A 20-mu mol/L threshold citrullinemia, (1) clas sified short bowel patients with permanent intestinal failure with high sen sitivity (92%), specificity (90%), positive predictive value (95%), and neg ative value (86%); and (2) was a more reliable indicator (odds ratio, 20.0; 95% confidence interval, 1.9-206.1) than anatomic variables (odds ratio, 2 .9; 95% confidence interval, 0.5-15.8) to separate transient as opposed to permanent intestinal failure. Conclusions: In patients with short-bowel syn drome, postabsorptive plasma citrulline concentration is a marker of functi onal absorptive bowel length and, past the a-year adaptive period, a powerf ul independent indicator allowing distinction of transient from permanent i ntestinal failure.