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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. LURD transplants were associated with excellent one-year graft survival of 92%. This survival was superior to that for cadaver transplants performed during the same period. 2. High-risk groups for LURDs are children (age < 18 years) and repeat transplant recipients. Both groups were associated with significantly decreased graft survival. 3. The effects of HLA matching and donor-specific transfusions are not significant. 4. Because of the critical shortage of donor organs and the increasing waiting time for renal transplantation, the use of LURDs can be recommended as a means to expand the number of available organs.

The proper management of surgical complications after simultaneous pancreas-kidney transplantation is essential to minimize morbidity. The almost universal acceptance of bladder drainage has shifted the complications after pancreatic transplantation from intra-abdominal to urologic. Most urologic complications will respond to conservative therapy. However, the early conversion to enteric drainage can be safely utilized when conservative therapy fails.

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.

1. Quadruple immunosuppression yields excellent early renal allograft survival in primary renal transplant recipients when compared with non-primary renal transplant recipients. Although significant, the difference between primary and nonprimary recipients at 5 years has narrowed considerably (8%). 2. No beneficial effect of HLA or DR matching was noted in this study in primary transplant recipients. However, a trend toward improved graft survival was noted when patients with greater than or equal to 3 antigens matched or less than 3 antigens mismatched were compared to their counterparts. Further analysis of variables related to graft loss is required before statements regarding this trend can be made. 3. Significantly better results in nonprimary renal transplantation continues to be seen in DR matched recipients. Additionally, the use of OKT3 rather than ALG in DR matched recipients has resulted in a 92.3% 3-year allograft survival despite over half of these patients being highly sensitized. 4. Further follow-up of 2 high-risk groups of patients (diabetics and elderly patients) revealed significant decreases in patient survival at 5 years. This difference was not apparent in our earlier results (3-year follow-up) published in Clinical Transplants 1987. Despite this difference, we believe renal transplantation should continue to be offered to diabetic and elderly patients without other contraindications to transplantation. 5. The availability of the monoclonal antibody OKT3 during the CsA era has resulted in a trend toward improved patient and graft survival when compared with patients in the CsA pre-OKT3 era. This trend toward improved survival is also seen in the high-risk diabetic recipients.

The data presented demonstrate that combined kidney-pancreas grafting can be performed with excellent patient and graft survival. Current long-term studies at our center investigating the effect of pancreas transplantation on diabetic retinopathy and comprehensive quality of life assessment will address the question of whether pancreas transplantation can be considered an effective and therapeutic procedure.

The data presented in this chapter demonstrate that acceptable short-term results can now be achieved for patients receiving a pancreas transplant. We feel that urinary drainage and the use of a whole pancreas with a duodenal segment currently represent the most optimal technical approach. Immunosuppressive therapy using the quadruple induction protocol will prevent early rejection episodes in the majority of patients. Once rejection is diagnosed, one should not hesitate to institute immediate antirejection treatment with OKT3 monoclonal antibody. In our most recent series of 24 combined kidney and pancreas transplants an extremely encouraging outcome can be reported. Of the 24 patients who received a combined cadaver kidney and pancreatic allograft within the last 2 years, 23 are alive and well. Twenty-three also have good-functioning kidneys, of which 21 have a functioning kidney and pancreatic allograft. Based on these results, which will undoubtedly be duplicated in the very near future by a number of other centers, we believe that pancreas transplantation has now emerged into a therapeutic and effective procedure.