Rejection diagnosis
Trends in serum citrulline and acute rejection among recipients of small bowel transplants

https://doi.org/10.1016/j.transproceed.2003.12.007Get rights and content

Abstract

A test for detecting acute cellular rejection (ACR) of small intestinal transplants (ITx) would be a major advance. Small preliminary studies suggest that serum citrulline levels correlate with ACR. The results for a group of 26 isolated intestinal and multivisceral transplant recipients are summarized here. Serum citrulline concentrations were determined by ion exchange chromatography and compared to biopsy-based grade of ACR. Other factors considered included patient and donor age and sex, ischemia time, and serum creatinine. Straight-line fits were employed to describe how each patient's citrulline levels changed over time. Estimated times to achieve normal citrulline (≥30 μmol/L) ranged from 1 to 730 days posttransplant for 21 patients demonstrating increasing citrulline levels over time. Using stepwise linear regression, patients' ranks for time required to achieve normal citrulline levels were the only independent predictors of both maximum ACR (P < .0001) and average ACR (P = .0059) after 14 days posttransplant. The rate and direction of change in citrulline over time may be an indicator of the risk of acute rejection. We plan to further examine the use of citrulline as a marker for rejection in larger prospective studies.

Section snippets

Methods

Analysis of serum citrulline levels was carried out by ion-exchange chromatography with serum concentrations compared to biopsy-based grades of rejection. Histopathologic grading of endoscopic biopsies was used to diagnose rejection. Severity of rejection was graded from 0 (none) to 4 (severe) following the criteria of the Small Bowel Allograft Working Group.5 Patients were selected for statistical analysis based on their having at least two citrulline levels between postoperative days 30 to

Results

Out of our pool of 32 patients, 26 were found to have adequate data for our analysis. These patients underwent transplants between December 1998 and October 2001 and consisted of 12 pediatric patients and 14 adults having undergone 14 small bowel, 11 multivisceral, and one liver/small bowel transplants. In total, we have acquired 14 pretransplant samples taken within 24 hours before surgery, 15 control specimens from healthy volunteers, 194 posttransplant samples taken within 24 hours of

Conclusions

This analysis has demonstrated that decreasing or slowly increasing citrulline levels correlate with higher grades of rejection, while a patient achieving citrulline levels > 30 μmol/L in less than 90 days correlates with lower grades of acute cellular rejection after this period. As such, the rate and direction of change in serum citrulline levels over time can be a criterion for allograft health and risk of rejection. We find our results to date encouraging and we are vigorously pursuing

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