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Antibody-mediated rejection (AMR) after pancreas transplantation is a recently identified entity. We describe the incidence of, risk factors for, and outcomes after AMR, and the correlation of C4d immunostaining and donor-specific antibody (DSA) in the diagnosis of AMR. We retrospectively analyzed 162 pancreas transplants in 159 patients who underwent 94 pancreas allograft biopsies between 2006 and 2009. Univariate and multivariate analyses were performed to evaluate risk factors for pancreas graft AMR. One-year rejection rates and survival after rejection were calculated by Kaplan-Meier methods. AMR occurred in 10% of patients by 1-year posttransplant. Multivariate risk factors identified for AMR include nonprimary simultaneous pancreas-kidney (SPK) transplant, primary solitary pancreas (PAN) transplant and race mismatch. After pancreas rejection, patient survival was 100% but 20% (8 of 41) of pancreas grafts failed within 1 year. Graft survival after acute cellular rejection (ACR), AMR and mixed rejection was similar. Of biopsies that stained >5% C4d, 80% were associated with increased Class I DSA. In summary, AMR occurs at a measurable rate after pancreas transplantation, and the diagnosis should be actively sought using C4d staining and DSA levels in patients with graft dysfunction, especially after nonprimary SPK and primary PAN transplantation., (© Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Since 1984, we have performed 243 living-unrelated renal transplants at the University of Wisconsin. Rejection occurred in 47% of the patients. Graft loss occurred in 59 patients and 39 patients died. Graft survival in LURD transplants at 10 years is 54% and 43% at 15 years. Patient survival is 68% at 10 years and 54% at 15 years. These long-term results demonstrate that LURD is equivalent to haploidentical renal transplantation and superior to cadaveric transplantation. Husband-to-wife donation demonstrated improved graft survival when compared with wife-to-husband and nonspousal donation. Living-unrelated renal transplantation has been utilized successfully at the University of Wisconsin and may help to alleviate the donor shortage.

Based on the University of Wisconsin experience with 653 cadaver pancreas transplant performed since 1985, we noted that: 1. The overall 5- and 10-year patient survival rates were 87% and 80%, respectively. The 5- and 10-year pancreas graft survival rates were 70% and 60%, respectively, and the 5- and 10-year kidney graft survival rates were 80% and 60%, respectively. 2. An immunosuppressive regimen including TAC and MMF in both solitary pancreas and SPK transplants was very effective in reducing the rate of acute rejection and improving graft survival. 3. Pancreas graft survival in recipients of solitary pancreas transplants was equivalent to that in SPK recipients in the TAC-MMF era. 4. Anti-IL2 receptor monoclonal antibodies were safe and effective in solitary pancreas and SPK transplants. 5. Excellent short-term graft survival can be achieved in solitary pancreas transplants using enteric drainage.

The data show that with careful surgical technique, modern immunosuppression with MMF and FK506, and pancreatic allograft biopsy, it should be possible to achieve: 1) a low rate of technical complications, 2) improved long-term graft survival, particularly in solitary pancreas recipients improving the risk/benefit ratio of this option for nonuremic diabetics, 3) a high safety profile with combined MMF and FK506 immunosuppression, 4) safe transplantation using enteric drainage without increased risk of rejection, infection or graft loss, and 5) successful pancreas transplantation without induction therapy.

After a decade of rapid development, SPK transplantation has become routine at our center. There are several developments responsible for the current high level of success: UW preservation solution, improved surgical technique, advances in immunosuppression, and expeditious diagnosis and treatment of complications. The critical modifications in surgical technique have included the avoidance of systemic heparinization, complete mobilization of the iliac vein for a tension-free anastomosis between an unmodified donor portal vein and the recipient iliac vein, oversewing of the revised duodenal staple lines and meticulous hemostasis. The most important recent improvement in immunosuppression is the use of mycophenolate mofetil, which has dramatically reduced rejection. Finally, PDC leaks, the principal and potentially most devastating complication of SPK transplantation, are rapidly diagnosed and treated expeditiously.

1. Immunological graft loss in the cyclosporine (CsA) era has been decreasing over the past decade with current 94% immunological graft survival at one year. 2. The rates of both immunological graft loss and graft loss from all causes gradually decrease after the first year for primary transplants. This implies that rejection gradually becomes less likely between one and 10 years follow-up. 3. On CsA immunosuppression, better DR matching results in significantly less immunological graft loss and a slower rate of late graft loss. 4. Roughly equal proportions of cadaveric renal transplants are lost due to acute rejection, chronic rejection, and death with a functioning graft (25-30% each). 5. Improving immunological graft outcome correlates with a lower incidence of a first rejection episode. Although OKT3 increases the success of rejection treatment, having a rejection episode nevertheless increases one's risk of immunological graft loss. 6. Cardiovascular deaths are by far the leading cause of mortality (42%) in this series. Improved strategies of prevention and treatment of cardiovascular disease are needed in this patient group. 7. Long-term CsA immunosuppression usually is not associated with graft loss due to CsA toxicity. Late graft loss from acute and chronic rejection is far more common, implying the need for continued immunosuppression even in patients with long-surviving grafts. 8. There is no measurable benefit of 3 or more random blood transfusions prior to cadaveric renal transplantation in the CsA era.

1. Use of LUrDs under a DST protocol results in a 70% actuarial graft survival at 6 years which is not statistically different from haploidentical or primary cadaver recipients transplanted over the same time period. 2. Sensitization is common, despite the use of Aza, especially in husband-to-wife donor-to-recipient relationship. 3. Rejection occurs frequently, despite the use of DST, however, it is usually reversible. The high rejection rate did not influence the quality of long-term graft survival with very few patients losing grafts to chronic rejection. 4. Expansion of the use of LUrDs could help provide additional organs for transplantation.

We have tested the predictive model for risk of sensitization by donor-specific transfusions developed at the University of California, San Francisco for its applicability to the DST experience at UW/Madison. Patient sample sizes between the two groups were similar (n = 249 for UW/Madison, n = 261 for UCSF) and the two groups of patients had similar compositions in terms of mean age, ABO type, baseline panel-reactive antibody, and pregnancy rate. The two groups differed in that the UW/Madison group had a higher percentage of males, diabetic patients, previously transplanted patients, and 0 haplotype-matched (2 HLA-mismatched related and unrelated) recipients. In addition, all the UW/Madison patients received azathioprine (AZA) whereas only half the UCSF group was given AZA. Despite these differences, application of the UCSF model for prediction of sensitization by DST gave remarkably similar results in our patient population, with pregnancy, prior transplant, baseline PRA, and HLA antigen sharing giving similar odds ratios and P values. However, when female sex was included in the model along with the other variables, the significance of pregnancy risk disappeared. We have developed an alternative multivariate model using stepwise logistic regression that identifies baseline PRA greater than 40%, female sex, and prior transplant as significant risk factors for sensitization, while number of HLA (A, B, DR) antigens shared and increasing recipient age significantly decreased risk of sensitization by DST.