Lessons learned from more than 1,000 pancreas transplants at a single institution

Abstract

Objective: To determine outcome in diabetic pancreas transplant recipients according to risk factors and the surgical techniques and immunosuppressive protocols that evolved during a 33-year period at a single institution.

Summary background data: Insulin-dependent diabetes mellitus is associated with a high incidence of management problems and secondary complications. Clinical pancreas transplantation began at the University of Minnesota in 1966, initially with a high failure rate, but outcome improved in parallel with other organ transplants. The authors retrospectively analyzed the factors associated with the increased success rate of pancreas transplants.

Methods: From December 16, 1966, to March 31, 2000, the authors performed 1,194 pancreas transplants (111 from living donors; 191 retransplants): 498 simultaneous pancreas-kidney (SPK) and 1 simultaneous pancreas-liver transplant; 404 pancreas after kidney (PAK) transplants; and 291 pancreas transplants alone (PTA). The analyses were divided into five eras: era 0, 1966 to 1973 (n = 14), historical; era 1, 1978 to 1986 (n = 148), transition to cyclosporine for immunosuppression, multiple duct management techniques, and only solitary (PAK and PTA) transplants; era 2, 1986 to 1994 (n = 461), all categories (SPK, PAK, and PTA), predominantly bladder drainage for graft duct management, and primarily triple therapy (cyclosporine, azathioprine, and prednisone) for maintenance immunosuppression; era 3, 1994 to 1998 (n = 286), tacrolimus and mycophenolate mofetil used; and era 4, 1998 to 2000 (n = 275), use of daclizumab for induction immunosuppression, primarily enteric drainage for SPK transplants, pretransplant immunosuppression in candidates awaiting PTA.

Results: Patient and primary cadaver pancreas graft functional (insulin-independence) survival rates at 1 year by category and era were as follows: SPK, era 2 (n = 214) versus eras 3 and 4 combined (n = 212), 85% and 64% versus 92% and 79%, respectively; PAK, era 1 (n = 36) versus 2 (n = 61) versus 3 (n = 84) versus 4 (n = 92), 86% and 17%, 98% and 59%, 98% and 76%, and 98% and 81%, respectively; in PTA, era 1 (n = 36) versus 2 (n = 72) versus 3 (n = 30) versus 4 (n = 40), 77% and 31%, 99% and 50%, 90% and 67%, and 100% and 88%, respectively. In eras 3 and 4 combined for primary cadaver SPK transplants, pancreas graft survival rates were significantly higher with bladder drainage (n = 136) than enteric drainage (n = 70), 82% versus 74% at 1 year (P =.03). Increasing recipient age had an adverse effect on outcome only in SPK recipients. Vascular disease was common (in eras 3 and 4, 27% of SPK recipients had a pretransplant myocardial infarction and 40% had a coronary artery bypass); those with no vascular disease had significantly higher patient and graft survival rates in the SPK and PAK categories. Living donor segmental pancreas transplants were associated with higher technically successful graft survival rates in each era, predominately solitary (PAK and PTA) in eras 1 and 2 and SPK in eras 3 and 4. Diabetic secondary complications were ameliorated in some recipients, and quality of life studies showed significant gains after the transplant in all recipient categories.

Conclusions: Patient and graft survival rates have significantly improved over time as surgical techniques and immunosuppressive protocols have evolved. Eventually, islet transplants will replace pancreas transplants for suitable candidates, but currently pancreas transplants can be applied and should be an option at all stages of diabetes. Early transplants are preferable for labile diabetes, but even patients with advanced complications can benefit.

Figure 1. Number of pancreas transplants according to recipient category (SPK, simultaneous pancreas–kidney; PTA, pancreas transplant alone; PAK, pancreas after kidney; SPL, simultaneous pancreas–liver) from living related donors (LRD) or living unrelated donors (LURD). Inclusive dates are December 16, 1966, to March 31, 2000.

Figure 10. Change in total quality of life (QOL) scores by quartile from before the transplant to 1 year after the transplant for (A) simultaneous pancreas–kidney, (B) pancreas after kidney, and (C) pancreas transplant alone recipients with functioning versus failed pancreas grafts.

Figure 2. Primary cadaver simultaneous pancreas–kidney transplant (A) patient, (B) pancreas graft, and (C) kidney graft functional survival rates and (D) pancreas graft rejection failure rates for era 2 versus eras 3 and 4 combined.

Figure 3. Primary cadaver pancreas after kidney transplant (A) patient and (B) pancreas graft functional survival rates and (C) pancreas graft rejection failure rates for era 1 versus era 2 versus eras 3 and 4 combined.

Figure 4. Primary cadaver pancreas transplant alone (A) patient and (B) pancreas graft functional survival rates and (C) pancreas graft rejection failure rates for era 1 versus era 2 versus eras 3 and 4 combined.

Figure 5. (A) Patient and (B) kidney graft survival rates in era 2 for primary cadaver simultaneous pancreas–kidney transplant versus cadaver or living donor kidney transplant alone; (C) patient and (D) kidney graft survival rates in eras 3 and 4 combined for the same categories.

Figure 6. Kidney graft survival rates in era 2 for cadaver pancreas after kidney transplant (PAK) recipients with cadaver kidneys versus cadaver kidney transplant alone (KTA) from the time of the (A) kidney transplant or (B) pancreas transplant (in PAK); and for primary cadaver PAK recipients with living donor kidneys versus living donor KTA from the time of the (C) kidney transplant or (D) pancreas transplant (PAK).

Figure 7. Kidney graft survival rates in eras 3 and 4 combined for primary cadaver pancreas after kidney transplant (PAK) recipients with cadaver kidneys versus cadaver kidney transplant alone (KTA) from the time of the (A) kidney or (B) pancreas transplant (PAK); and for primary cadaver PAK recipients with living donor kidneys versus living donor KTA from the time of the (C) kidney transplant or (D) pancreas transplant (PAK).

Figure 8. Functional survival rates of technically successful pancreas grafts from living donor versus cadaver donors for pancreas after kidney transplant recipients in (A) era 1 and (B) era 2 and for pancreas transplant alone recipients in (C) era 1 and (D) era 2.

Figure 9. Patient, pancreas, and kidney graft survival rates in all simultaneous pancreas–kidney transplant recipients of both grafts from a living donor.