Histologic grading of acute allograft rejection in pancreas needle biopsy:Correlation to serum enzymes, glycemia, and response to immunosuppressive treatment

Background Allograft rejection continues to be the most common cause of gra ft failure in technically successful pancreas transplants. Early diagnosis and treatment of rejection is essential for long-term graft survival. Pancr eas graft biopsies are now used routinely for the diagnosis of acute allogr aft rejection. The correlation between clinical evidence of graft dysfuncti on (increased serum enzymes and glucose), severity of acute rejection on bi opsy (rejection grade), and response to treatment has not been previously s tudied. Methods. A total of 151 pancreas transplant needle biopsy specimens from 57 patients were evaluated. Statistical correlation was done between the hist ologic rejection grade (0-V) and the peak level of enzymes in serum, glycem ia, type of antirejection treatment instituted, and response to treatment. Differentiation between grades was also evaluated statistically. Results. Response to antirejection treatment was 25%, 40%, 88%, 78%, 50%, a nd 17% for grades 0-V, respectively. The response for grades II and III was better than for grades 0-I and IV-V (P=0.0003 and 0.0008, respectively). T he response to corticosteroids alone was 36%, 86%, 68%, and 0% for grades I , II, III, and IV, respectively. The response to antilymphocyte regimen was 50%, 89%, 85%, 71%, and 17% for grades I, II, III, TV, and V, respectively . Overall correlation between the mean levels of enzymes and rejection grad e was seen; the increase of lipase was statistically significant (r=0.24, P =0.012). Amylase and lipase correlated very well with each other (r=0.84, P =0.0001). No correlation was found in the mean values of blood glucose with the serum enzyme increase and with severity of rejection. Hyperglycemia wa s present in 12 patients; this abnormality in patients with grades II-TV re sponded promptly to treatment, whereas in patients with grade V, hyperglyce mia persisted despite antirejection treatment. Other causes of increased en zymes were found in patients with biopsy specimens showing no rejection (gr ades 0 and I, 43% and 31%, respectively). Conclusions. Increased serum enzymes, particularly lipase, correlate with t he grade of acute rejection, but their lack of specificity precludes their use as sole markers of acute rejection. Glucose levels are not a sensitive marker for acute rejection. Rejection grades II and III are the most respon sive to treatment, and a significant proportion of these cases respond to t reatment with corticosteroids only. The higher rejection grades (IV and V) require treatment with antilymphocytic regimens, and their overall response to treatment is moderate to poor, respectively.