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Citrulline Level Is a Potent Indicator of Acute Rejection in the Long Term Following Pediatric Intestinal/Multivisceral Transplantation
Author(s) -
Hibi T.,
Nishida S.,
Garcia J.,
Tryphonopoulos P.,
Tekin A.,
Selvaggi G.,
Weppler D.,
Levi D. M.,
Ruiz P.,
Tzakis A. G.
Publication year - 2012
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2012.04155.x
Subject(s) - medicine , citrulline , cutoff , gastroenterology , transplantation , biomarker , biopsy , population , surgery , arginine , biochemistry , chemistry , physics , environmental health , amino acid , quantum mechanics
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 μmol/L) and moderate/severe ACR (cutoff, 10 μmol/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.