Pancreas function index: an early monitor of allograft rejection

The lack of reliable markers for the early diagnosis of allograft rejection is a major obstacle preventing improved results in clinical pancreas transplantation. Using a vascularized whole-pancreas transplant model in the rat, with exocrine ductal drainage into the lower urinary tract, we explored the possibility that a change in an index of pancreatic function (IPF), viz., urine volume, urine pH, and urine amylase (UA) in composite, may provide an earlier and more specific indicator of rejection than a decline in UA levels alone. Six Lewis-to-Lewis rat isograft and 12 ACI-to-Lewis allograft recipients were studied. Ten nontransplanted diabetic Lewis rats served as a control group. Euglycemia was restored in all the recipients of isografts, and was maintained for over a year. In the allograft group, rejection occurred on Days 7-9, with a mean graft survival time of 8.1 +/- 0.1 days. Peak UA levels and IPF during normal allograft function were 2422 +/- 353 U/ml and 100 +/- 14, respectively, whereas levels heralding rejection were 600 U/ml and 25 (P less than 0.05). The diagnosis of rejection based on the IPF resulted in significantly greater specificity and an earlier prediction time compared with UA alone (2.4 +/- 0.3 vs 1.6 +/- 0.2 days); the IPF permitted the successful prediction of rejection 3 or more days prior to hyperglycemia in 6 of 12 (50%) grafts, whereas only 1 of 12 (8%) rejection episodes was successfully predicted when the rejection criterion was based on UA. In conclusion, early diagnosis of rejection was achieved by a composite index of pancreatic function, improving the ability to predict pancreas-allograft rejection 24 to 48 hr prior to a fall in UA levels.