Citrulline level is a potent indicator of acute rejection in the long term following pediatric intestinal/multivisceral transplantation.
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.
Miami Transplant Institute, University of Miami and Jackson Memorial Hospital, Miami, FL, USA.
T
T
Hibi
S
S
Nishida
J
J
Garcia
P
P
Tryphonopoulos
A
A
Tekin
G
G
Selvaggi
D
D
Weppler
D M
DM
Levi
P
P
Ruiz
A G
AG
Tzakis
D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D002956:Citrulline / Q000097:blood*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000097:blood* / Q000175:diagnosis*; D006801:Humans; D007223:Infant; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000473:pathology / Q000637:transplantation*; D008137:Longitudinal Studies; D008297:Male; D016377:Organ Transplantation; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012189:Retrospective Studies; D012720:Severity of Illness Index; D014781:Viscera / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*
D015415:Biomarkers; D002956:Citrulline