title: Histologic grading of acute allograft rejection in pancreas needle biopsy: correlation to serum enzymes, glycemia, and response to immunosuppressive treatment.
abstract: BACKGROUND
  Allograft rejection continues to be the most common cause of graft failure in technically successful pancreas transplants. Early diagnosis and treatment of rejection is essential for long-term graft survival. Pancreas graft biopsies are now used routinely for the diagnosis of acute allograft rejection. The correlation between clinical evidence of graft dysfunction (increased serum enzymes and glucose), severity of acute rejection on biopsy (rejection grade), and response to treatment has not been previously studied.
  
  
  METHODS
  A total of 151 pancreas transplant needle biopsy specimens from 57 patients were evaluated. Statistical correlation was done between the histologic rejection grade (O-V) and the peak level of enzymes in serum, glycemia, 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%, and 17% for grades O-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). The 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, IV, and V, respectively. Overall correlation between the mean levels of enzymes and rejection grade 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 was present in 12 patients; this abnormality in patients with grades II-IV responded promptly to treatment, whereas in patients with grade V, hyperglycemia persisted despite antirejection treatment. Other causes of increased enzymes were found in patients with biopsy specimens showing no rejection (grades 0 and I, 43% and 31%, respectively).
  
  
  CONCLUSIONS
  Increased serum enzymes, particularly lipase, correlate with the 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 responsive to treatment, and a significant proportion of these cases respond to treatment 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.
authors.affiliation: Department of Pathology, University of Maryland School of Medicine, Baltimore 21201, USA. jpapa001@umaryland.edu
authors.forename: J C
authors.initials: JC
authors.lastname: Papadimitriou
authors.forename: C B
authors.initials: CB
authors.lastname: Drachenberg
authors.forename: A
authors.initials: A
authors.lastname: Wiland
authors.forename: D K
authors.initials: DK
authors.lastname: Klassen
authors.forename: J
authors.initials: J
authors.lastname: Fink
authors.forename: M R
authors.initials: MR
authors.lastname: Weir
authors.forename: C
authors.initials: C
authors.lastname: Cangro
authors.forename: E J
authors.initials: EJ
authors.lastname: Schweitzer
authors.forename: S T
authors.initials: ST
authors.lastname: Bartlett
mesh_terms: D000208:Acute Disease; D000328:Adult; D000681:Amylases / Q000097:blood*; D001707:Biopsy, Needle; D001786:Blood Glucose / Q000032:analysis*; D005260:Female; D006084:Graft Rejection; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008049:Lipase / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000473:pathology*; D016035:Pancreas Transplantation; D014184:Transplantation, Homologous
chemical_list: D001786:Blood Glucose; D007166:Immunosuppressive Agents; D008049:Lipase; D000681:Amylases