Prognostic risk factors for graft failure following pancreas transplantation: results of multivariate analysis of data from the International Pancreas Transplant Registry

Viste, Asgaut; Moudry-Munns, K.; Sutherland, David E.R.

doi:10.1007/bf00336212

Cited by 10 publications

(4 citation statements)

References 10 publications

(1 reference statement)

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“…Most pancreas transplants are performed simultaneous with a kidney, and the benefit conferred by having akidney from the samedonor to monitor forrejection may override any advantage that one duct management technique has over another. The dominant effect of kidney association and the lack of a significant influence of duct management on outcome is consistent with a previous multivariate analysis of Registry data (Viste et al 1990).…”

Section: Discussionsupporting

confidence: 90%

Report from the International Pancreas Transplant Registry

Sutherland

1991

Diabetologia

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From December, 1966 through 1990, 3082 pancreas transplants were reported to the International Registry. A detailed analysis was performed on the 2087 transplants in the 1986-90 data base; during this time the overall one year recipient and graft functional survival rates were 89% and 62%. Univariate analyses showed graft survival rates to be significantly higher with bladder drainage than with other duct management techniques, with a simultaneous kidney transplant than without, and with preservation in UW than other solutions. Storage up to 30 hours did not adversely effect results. Graft survival rates were significantly higher in North America than Europe, a discrepancy that persisted in a Cox proportional hazard analysis that also included duct management, recipient category, HLA-DR mismatching, immunosuppression with anti-T cell agents, preservation solution and duration, and year of transplant as the other variables; three were identified to have a significant (p less than 0.05) impact on the relative risk (RR) of graft loss: 1) Recipient category, with an RR of 0.43 when placed simultaneously with a kidney; 2) Year, with an RR of 0.76 for transplants performed in 1989-90 versus 1986-88; and 3) Location, with an RR of 0.75 for transplants in North America versus Europe. The technical failure rate was significantly lower in North America than Europe, but this was not an explanation for the differences in outcome, since the same factors sorted out as significant in a Cox proportional hazard analysis of technically successful cases only. Furthermore, logistic regression analysis showed retransplantation, duct management, recipient category, preservation solution, and storage time to significantly influence the technical failure rate. The risk of technical failure was lowest for primary, bladder-drained, simultaneous pancreas/kidney, less than 12 hour UW stored grafts; year and location of transplant were not significant factors. Pancreas transplant results continue to improve and are in the range of those for other solid organs.

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Section: Discussionsupporting

confidence: 90%

Report from the International Pancreas Transplant Registry

Sutherland

1991

Diabetologia

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“…[17][18][19] However, acute pancreas rejection occurring within the first 6 months with cyclosporine (CsA) combined with corticosteroid and azathioprine (AZA), despite the use of induction therapy, remains the most important barrier to the success and safety of pancreas transplantation. 19,20 It has been shown that rejection episodes occur more frequently after pancreas-kidney transplantation compared with kidney transplantation alone, causing an increased in the rate of hospitalization, the use of antilymphocyte agents, and infection-related morbidity. [20][21][22][23] According to registry data, rejection accounts for 32% of graft failures in the 1st year after pancreas transplantation.…”

confidence: 99%

“…19,20 It has been shown that rejection episodes occur more frequently after pancreas-kidney transplantation compared with kidney transplantation alone, causing an increased in the rate of hospitalization, the use of antilymphocyte agents, and infection-related morbidity. [20][21][22][23] According to registry data, rejection accounts for 32% of graft failures in the 1st year after pancreas transplantation. 15,16 However, improvements are expected to continue with the recent introduction of immunosuppressive agents tacrolimus (TAC) and mycophenolate mofetil (MMF).…”

confidence: 99%

Comparison of Azathioprine and Mycophenolate Mofetil for the Prevention of Acute Rejection in Recipients of Pancreas Transplantation

Wiland

Klassen

et al. 2001

The Journal of Clinical Pharma

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The study was performed to compare the efficacy and side effects of azathioprine (AZA) and mycophenolate mofetil (MMF) in conjunction with cyclosporine or tacrolimus and steroids for the prevention of acute pancreas rejection during the first 6 months of pancreas transplantation. In this case-controlled study, MMF is compared with historical controls of AZA in the prevention of acute pancreas rejection. The primary measures of treatment efficacy were patient and pancreas survival rate at 6 months after transplantation. Secondary efficacy measures were the occurrence of biopsy-proven pancreas rejections and the use of antilymphocyte preparations for rejection treatment. A total of 111 pancreas transplant patients (57 in the AZA group and 54 in the MMF group) were evaluated. The 6-month patient survival rate was 96% in the AZA group versus 97% in the MMF group (p = 0.57). The 6-month pancreas graft survival rate was 88% in the AZA group versus 91% in the MMF group (p = 0.29). However, biopsy-proven rejection episodes during the first 6 months of transplantation were significantly lower with MMF (46%) than with AZA (69%) (p = 0.01). In addition, patients in the AZA group received a greater number of full courses of antilymphocyte therapy as a rejection treatment (p = 0.004). Overall, the frequency of adverse events was similar, although the MMF group experienced higher incidences of gastrointestinal adverse events. In conclusion, compared with AZA, MMF significantly reduces the rate of biopsy-proven pancreas rejection during the first 6 months of transplantation and is well tolerated, except for gastrointestinal adverse events.

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“…With the use of these drugs, most pancreas transplant centers reported rates of acute rejection ranging from 60 to 80% [4–19]. Risk factors for acute rejection included solitary pancreas transplantation, pancreas retransplantation, HLA mismatching, and the absence of antibody induction therapy [20–23]. However, recent developments in immunosuppressive therapy offer significant promise for reducing the risk of acute rejection and further enhancing long‐term graft survival.…”

Section: Maintenance Immunosuppressionmentioning

confidence: 99%

Review of immunosuppressive usage in pancreas transplantation

Stratta

1999

Clinical Transplantation

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Throughout 1997, nearly 10,000 pancreas transplants have been performed worldwide, with 88% being simultaneous kidney transplants (SKPT). The current 1 yr patient survival rate exceeds 90% and pancreas graft survival (complete insulin independence) rate exceeds 80% for SKPT, 70% for sequential pancreas after kidney transplant (PAKT), and 65% for pancreas transplant alone (PTA). According to registry data, rejection accounts for 32% of graft failures in the first year after pancreas transplantation. However, improvements are expected to continue with the evolution of treatment protocols. Most pancreas transplant centers employ quadruple drug immunosuppression with anti-lymphocyte induction with either a monoclonal or polyclonal antibody agent. In recent years, there has been an overall decline in the use of antibody induction therapy from 90% during the period 1987-1993 to 83% of pancreas transplants performed during 1994-1997. Maintenance immunosuppression is triple therapy consisting of a calcineurin inhibitor (cyclosporine or tacrolimus), corticosteroids, and an anti-metabolite (AZA or MMF). Prior to 1995, nearly all pancreas transplant recipients were managed with Sandimmune. In the last 2 yr, tacrolimus-based therapy has been used in approximately 20% of cases and a new microemulsion formulation of cyclosporine (Neoral) has replaced Sandimmune in contemporary post-transplant immunosuppression. In addition, MMF is replacing AZA as part of the standard immunosuppressive regimen after pancreas transplantation. At present, a number of centers are conducting various trials with new drug combinations including either Neoral or tacrolimus in combination with steroids and MMF with or without antibody induction therapy. From 1994 to 1997, the 1 yr rates of immunologic graft loss have decreased to 2% after SKPT, 9% after PAKT, and 16% after PTA. The current array of new immunosuppressive agents are providing more effective control of rejection and permitting solitary pancreas transplantation to become an accepted treatment option in diabetic patients without advanced complications. The apparent potency of new drug combinations has also resulted in a resurgence of interest in steroid withdrawal. Immunosuppressive strategies will continue to evolve in order to achieve effective control of rejection while minimizing injury to the allograft and risk to the patient. In addition, new regimens must not only address the issue of specific drug toxicities but also long-term economic, metabolic, and quality of life outcomes. Pancreas transplantation will remain an important alternative in the treatment of diabetic patients until other strategies are developed that can provide equal glycemic control with less immunosuppression and overall morbidity.

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Prognostic risk factors for graft failure following pancreas transplantation: results of multivariate analysis of data from the International Pancreas Transplant Registry

Cited by 10 publications

References 10 publications

Report from the International Pancreas Transplant Registry

Report from the International Pancreas Transplant Registry

Comparison of Azathioprine and Mycophenolate Mofetil for the Prevention of Acute Rejection in Recipients of Pancreas Transplantation

Review of immunosuppressive usage in pancreas transplantation

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