EARLY PANCREAS GRAFT FAILURE AFTER SIMULTANEOUS PANCREAS KIDNEY
TRANSPLANTATION
H. de Kort1, M.J.K. Mallat3, C. van Kooten3, E. de Heer1, S.H. Brand-Schaaf2, A.M. v.d. Wal1, D.L.
Roelen2, J.A. Bruijn1, F.H. Claas2, H.W. de Fijter3, I.M. Bajema1
Department of Pathology1, Immunohematology and Blood Transfusion2, and Nephrology3 Leiden
University Medical Center, Leiden, the Netherlands
Objectives: Pancreas transplantation, primarily performed as simultaneous pancreas kidney
transplantation (SPKT), is a well-established cure for diabetes. Many improvements were made since the
first pancreas transplantation in 1966, resulting in a long-term survival advantage. However, SPKTs are
still faced with both immunological and non-immunological graft loss. Graft failure within 1 year is worse
for the pancreas than for the kidney in SPKT. Early loss of the pancreas graft is clinically mostly attributed
to technical failure, encompassing loss through vascular thrombosis, anastomotic leaks, bleeding,
pancreatitis, or infection. Until now, there has been little attention for the role of antibody-mediated
rejection (AMR) in pancreas graft loss. The aim of the present study was to investigate how many early
pancreas graft losses within 1 year after transplantation were due to AMR.
Methods: At Leiden University Medical Center, a total of 256 pancreas transplantations were performed
between 1985 and February 2010, of which 59 resulted in graft failure and transplantectomy. Fourty-two
failed within 1 year, and we were able to include 33 SPKT pancreata within this study (excluded were
patients with pancreas after kidney transplantation or pancreas transplantation alone (n=3), patients with
graft loss due to post transplant lympho-proliferative disease (n=2), and tissue samples with extensive
damage unsuitable for Banff scoring (n=4)). Immunohistochemistry for C4d, CD3, CD20, CD68, BK-virus,
and CMV was performed on paraffin-embedded tissue samples. HE-slides were scored according to the
Banff ‘08 working proposal for classification. Histological components scored for were; active septal
inflammation, (peri)neural inflammation, ductitis, venulitis, interacinar capillaritis, acinar inflammation,
acinar cell injury/ necrosis, intimal arteritis, necrotizing arteritis, and transplant arteriopathy. In most cases,
pre-transplantation and post-transplantectomy (27 out of 33) DSA serology results were available or
additional tests were performed.
Results: C4d-staining was negative in 19 cases, focally positive in 6 cases, and diffusely positive in 8
cases. DSA were found after transplantectomy in 8 out of 27 patients, none of the patients had DSA prior
to transplantation. In 4 patients both DSA after transplantation and diffuse C4d staining in the excised
pancreas graft were found, which established the diagnosis of a true AMR in these 4 patients. There were
14 patients without C4d depositions in their lost grafts and no DSA detected after transplantectomy: in
these patients the graft was lost due to other causes than AMR. There were 9 patients with a suspected
AMR in their lost grafts: they either had DSA alone (i.e. in the absence of C4d positivity), diffuse C4d
positivity without DSA, or focal C4d positivity either with or without DSA. True AMR, diffuse C4d positivity,
or DSA on their own correlated with interacinar capillaritis. True AMR was significantly correlated with the
total number of rejection episodes. DSA positivity was also significantly correlated with acinar
inflammation and (peri)neural inflammation. Immunohistochemical parameters CD3, CD20 and CD68 did
not contribute to the diagnosis AMR. All grafts were negative for BK-virus and CMV. Of the 4 true AMR
patients, 3 lost their kidney graft on average 1.5 months prior to their pancreas and 1 lost his kidney 4
months after the pancreas was lost.
Conclusions: In 4 out of the 33 pancreas graft losses included in this study, true AMR was found
characterized by presence of DSA, diffuse C4d staining patterns and with interacinar capillaritis as a
prominent histological parameter. Our finding provides evidence that AMR can be the cause of early
pancreas graft loss. Furthermore, a substantial number of the pancreas transplantectomies were
suspected for AMR, for instance on the basis of focal C4d deposition, either with or without DSA. AMR as
a cause for early graft loss in pancreas transplantation is an important differential diagnosis of technical
failure. Early recognition of AMR might provide means for therapeutic intervention, to prevent graft loss.