Citrulline level is a potent indicator of acute rejection in the long term following pediatric intestinal/multivisceral transplantation

T. Hibi, S. Nishida, J. Garcia, P. Tryphonopoulos, A. Tekin, G. Selvaggi, D. Weppler, D. M. Levi, P. Ruiz, A. G. Tzakis

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30 Citations (Scopus)


Citrulline has been advocated as a marker for acute cellular rejection (ACR) in intestinal transplantation; however, its significance as a forewarning in the long-term follow-up remains unknown. This study aimed to investigate the association between citrulline levels and the grading of ACR to establish a cutoff point that accurately predicts ACR beyond 3 months posttransplant in the pediatric patient population. During a 16-year period (1995-2011), a total of 13 499 citrulline samples were prospectively collected from 111 consecutive pediatric intestinal/multivisceral transplant recipients: 2155 were obtained concurrently with intestinal biopsies. There were 185 ACR episodes observed among 74/111 (67%) patients (median follow-up: 4.4 years). Citrulline levels were inversely proportional to the severity of ACR. Negative predictive values for any type of ACR (cutoff, 20 lmol/L) and moderate/severe ACR (cutoff, 10 lmol/L) were 95% and 99%, respectively. When patients were divided according to graft size, diagnostic accuracy using the same cutoff was identical. Similarly, subgroup analysis by the timing of citrulline measurement prior to biopsy varying from 1 to 7 days demonstrated comparable results. Citrulline is a potent indicator as a danger signal for ACR, being an exclusionary, noninvasive biomarker with excellent negative predictive values in the long term after pediatric intestinal/multivisceral transplant.

Original languageEnglish
Pages (from-to)S27-S32
JournalAmerican Journal of Transplantation
Issue numberSUPPL 4
Publication statusPublished - 2012
Externally publishedYes


  • Acute cellular rejection
  • Citrulline
  • Intestinal transplantation
  • Multivisceral transplantation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)


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