Blood citrulline level is an exclusionary marker for significant acute rejection after intestinal transplantation.
BACKGROUND
Serum citrulline is a marker for acute cellular rejection (ACR) after intestinal transplantation; however, its clinical utility has not yet been established. The goal of this study was to determine clearcut serum levels beyond which the diagnosis of acute rejection could be supported or refuted, and predictors of citrulline levels posttransplant from which more accurate estimates of sensitivity and specificity could be obtained.


METHODS
Since March 2004, we obtained 2135 dried blood spot (DBS) citrulline samples from 57 intestinal transplant recipients at or beyond 3 months posttransplant. Stepwise linear regression was performed to determine the most significant multivariable predictors of the patient's DBS citrulline level.


RESULTS
Seven characteristics were associated with a significantly lower citrulline in multivariable analysis: presence of mild, moderate, or severe ACR; presence of bacteremia or respiratory infection; pediatric age; and time from transplant to DBS sample (P<0.00001 in each case). Using a <13 vs. > or =13 micromoles/L cutoff point, the sensitivity for detecting moderate or severe ACR and the negative predictive value were high (96.4% and >99% respectively). Specificity was 54% to 74% in children and 83% to 88% in adults.


CONCLUSIONS
Citrulline levels <13 micromoles/L should alert the clinical team that a serious problem (rejection or infection) could be looming in a previously stable intestinal recipient. Levels > =13 micromoles/L practically rule out moderate or severe rejection.
David
Andre I
AI
Departments of Surgery, University of Miami School of Medicine, Miami, FL 33101, USA.
Selvaggi
Gennaro
G
Ruiz
Phillip
P
Gaynor
Jeffrey J
JJ
Tryphonopoulos
Panagiotis
P
Kleiner
Gary I
GI
Moon
Jang I
JI
Nishida
Seigo
S
Pappas
Peter A
PA
Conanan
Lobella
L
Weppler
Debbie
D
Esquenazi
Violet
V
Levi
David M
DM
Kato
Tomoaki
T
Tzakis
Andreas G
AG
D000208:Acute Disease; D015415:Biomarkers / Q000097:blood; D002956:Citrulline / Q000097:blood*; D005260:Female; D006084:Graft Rejection / Q000097:blood / Q000175:diagnosis*; D006801:Humans; D007422:Intestines / Q000637:transplantation*; D008297:Male; D012189:Retrospective Studies; D012680:Sensitivity and Specificity
D015415:Biomarkers; D002956:Citrulline