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.

Intestinal and multivisceral transplantation in children.

OBJECTIVE: To describe a single-center experience of pediatric intestinal transplantation (Itx) and to provide an overview of the children who underwent this procedure along with their outcomes. SUMMARY BACKGROUND DATA: Pediatric Itx presents multiple challenges because of the very young ages at which patients require transplantation and their higher susceptibility to infectious complications. METHODS: We have performed 141 Itx in 123 children with a median age of 1.37 years. Primary grafts included isolated intestine (n = 28), liver and intestine (n = 27), multivisceral (n = 61), and multivisceral without the liver (n = 7). Two protocol modifications were introduced in 1998: daclizumab induction and frequent rejection surveillance. In 2001, indications for multivisceral transplantation were expanded, and induction with Campath-1H was introduced. RESULTS: Actuarial patient survival at 1 and 3 years for group 1 (January 1994 to December 1997, n = 25), group 2 (January 1998 to March 2001, n = 29), group 3a (April 2001 to present, daclizumab, n = 51), and group 3b (April 2001 to present, Campath-1H, n = 18) was 44%/32%, 52%/38%, 83%/60%, and 44%/44%, respectively (P = 0.0003 in favor of group 3a). Severe rejection implied a dismal prognosis (65% mortality at 6 months). Observed incidence of severe rejection in groups 1, 2, 3a, and 3b was 32%, 24%, 14%, and 11%, respectively. In multivariable analysis, use of a multivisceral (with or without liver) transplant (P = 0.002), induction with daclizumab (P = 0.005), patient at home prior to transplant (P = 0.007), and age at transplant > or =1 year (P = 0.02) favorably influenced patient survival. Multivisceral transplant was protective with respect to the mortality rate due to rejection, while an older age at transplant was associated with both a lower incidence rate of developing respiratory infection and lower risk of mortality following the respiratory infection. Survivors are off parenteral nutrition and have demonstrated significant growth catch-up. CONCLUSIONS: Itx in children still is a high-risk procedure but has now become a viable option for children who otherwise have no hope for survival. Control of respiratory infection is of particular importance in the younger children.

100 multivisceral transplants at a single center.

OBJECTIVE: The objective of this study was to summarize the evolution of multivisceral transplantation over a decade of experience and evaluate its current status. SUMMARY BACKGROUND DATA: Multivisceral transplantation can be valuable for the treatment of patients with massive abdominal catastrophes. Its major limitations have been technical and rejection of the intestinal graft. METHODS: This study consisted of an outcome analysis of 98 consecutive patients who received multivisceral transplantation at our institution. This represents the largest single center experience to date. RESULTS: The most common diseases in our population before transplant were intestinal gastroschisis and intestinal dysmotility syndromes in children, and mesenteric thrombosis and trauma in adults. Kaplan Meier estimated patient and graft survivals for all cases were 65% and 63% at 1 year, 49% and 47% at 3 years, and 49% and 47% at 5 years. Factors that adversely influenced patient survival included transplant before 1998 (P = 0.01), being hospitalized at the time of transplant (P = 0.05), and being a child who received Campath-1H induction (P = 0.03). Among 37 patients who had none of these 3 factors (15 adults and 22 children), estimated 1- and 3-year survivals were 89% and 71%, respectively. Patients transplanted since 2001 had significantly less moderate and severe rejections (31.6% vs 67.6%, P = 0.0005) with almost half of these patients never developing rejection. CONCLUSIONS: Multivisceral transplantation is now an effective treatment of patients with complex abdominal pathology. The incidences of serious acute rejection and patient survival have improved in the most recent experience. Our results show that the multivisceral graft seems to facilitate engraftment of transplanted organs and raises the possibility that there is a degree of immunologic protection afforded by this procedure.