Anil Vaidya, Marion O'Connor, Lydia Smith, Doruk Elker, Reddy Srikant, Peter Friend

Oxford Transplant Center, Oxford, United Kingdom

Introduction: Citrulline has been successfully used as a marker for intestinal graft dysfunction after intestinal transplantation. We have extended its use to direct enteral versus parenteral feeding in the early post operative period as well as during graft dysfunction presenting as high volume stoma effluent.

Materials and Methods: Serum citrulline concentrations using Guthrie cards were implemented in directing nutrition in all recipients of intestinal grafts. A cut off of 18 micromol/l was used. Citrulline levels were done on a particular day of the week on a weekly basis starting from the day of transplant. Patients with citrulline levels less than 18mmol/l in the post operative period were kept on low volume enteral feed and maintained on TPN. The recipients were followed with weekly citrulline. Once the levels were above 18mmol/l, enteral feeds were advanced rapidly to goal and TPN independence was achieved. A similar pattern was followed with patients presenting with high output stomal effluents. Citrulline levels below 18mmol/l was a trigger for getting a tunneled line in and institution of TPN while the patient was having diagnostic tests done to look for a cause of the dysfunction. Citrulline levels of more than 18mmol/l with a high stomal output would be managed with enteral feed and replacement of salt and water for on going losses. These citrulline levels were then matched with histopathological diagnosis in the early post transplant period as well as during transient graft dysfunction.

Results: From October 2006 to date, 9 patients underwent a small bowel transplant at the Oxford transplant center. Mean citrulline levels in the first week after transplantation were 15mmol/l (range 12-17). Endoscopic biopsies in the first week showed signs of ischemia reperfusion with significant edema in the submucosa of the transplanted ileum. Mean ostomy effluent volumes were 800mls/24h (range 200-1800 mls). All these patients were maintained on TPN for the first week and had enteral feed (peptisorb) at 30 mls/h. Mean citrulline levels in the second week were 19 mmol/l (range 15-22). The patients who had crossed the 18 mmol/l mark were rapidly progressed on to full feeds and TPN discontinued. The biopsy from the patients with citrulline levels above 18mmol/l showed significant improvement in submucosal edema. 4 patients presented with intestinal dysfunction after discharge from the hospital. The first patient had a citrulline of 19mmol/l on presentation with a high stoma output. She was maintained on enteral feeding and fluid and electrolyte replacement for her losses. Biopsy demonstrated acute rejection that was successfully treated with methylprednisolone. The second patient presented with a high stoma output with a citrulline level of 9mmol/l. He was kept nil by mouth (NBM) and started on TPN immediately. Biopsy results revealed increase in mitotic figures as well as apoptosis and loss of tips of villi architecture. This was initially reported as rejection and treated with ATG after failure of steroids. The patient did not improve and succumbed to a pulmonary embolus. The third patient presented with a high stomal output and a citrulline of 18mmol/l. She was kept on enteral feeds and intravenous fluid and electrolyte replacement. Her biopsy showed signs of moderate rejection. She was subsequently treated with a dose of Campath. Her citrulline level fell further to 13 and then 9 mmol/l in subsequent weeks. She was then kept NBM and TPN instituted through a tunnelled line. She recovered from the episode of rejection and is presently off TPN and maintaining an oral diet. The fourth patient presented with a high output and citrulline levle of 13mmol/l, dropping further to 6mmol/l. He was kept NBM and TPN was started through a tunnelled line on admission. His biopsy revealed a similar picture to patient number 2 with dense mitotic activity in the face of increased apoptosis. Adenoviral PCR showed a four fold log increase and we decreased his maintainance immunosuppression. he recovered in a span of 30 days with subsequent citrulline showing a rise. he was then weaned off TPN and commenced on enteral feeds once he achieved a citrulline level of more than 18mmol/l. Mean time to graft dysfunction from transplantation was 240 days (range 46-450).

Conclusion: Firstly serum citrulline is a good marker to direct nutritional therapy in the early post transplant period as well as during graft dysfunction. Secondly, although the numbers are small there appears to be an association with lower presenting citrulline levels with infection as opposed to rejection, suggesting that infection is possibly global and rejection may be patchy.