Background. Graft rejection is one of the major causes of graft loss a
fter pancreas transplantation. Pancreatitis-associated protein (PAP) i
s synthesized by the pancreas due to pancreatic inflammation and has s
hown to be a good serum marker for injury of the pancreas. It may also
be potentially useful in the early recognition of rejection and may t
hus improve pancreas survival. Methods. We retrospectively evaluated P
AP as an early serum marker of pancreas graft rejection in a cross-sec
tional study in which immunohistochemical analysis of pancreas biopsie
s was undertaken using antibodies against PAP. PAP concentrations were
also measured in sera of blood donors and in patients with renal fail
ure, renal replacement therapy, kidney transplantation alone, and simu
ltaneous pancreas-kidney transplantation. Results. All patients had el
evated PAP serum levels compared with blood donors (median PAP: 22 ng/
ml, range: 5-75 ng/ml; P<0.0001). Patients on renal replacement therap
y had higher values than patients with renal failure (median: 420 ng/m
l and 150 ng/ml, respectively). There was a strong inverse correlation
between PAP levels and creatinine clearance (P<0.001). PAP values in
simultaneous pancreas-kidney transplantation patients with histologica
l rejection were significantly higher than values in those who were cl
inically stable (median: 925 ng/ml and 322 ng/ml, respectively; P=0.00
6). Rejection was significantly associated with PAP staining of acinar
cell surface. There was also a significant correlation between surfac
e positivity of staining and serum PAP levels (P=0.008). No positive P
AP staining was observed in concurrently collected biopsies of renal a
llografts undergoing rejection. Conclusions. Serum PAP levels appear t
o strongly correlate with creatinine clearance measurements. In patien
ts with a pancreas-kidney transplantation, PAP may prove to be a usefu
l biological and histological marker of pancreatic graft rejection.