ABSTRACT
UNLABELLED: To evaluate the risk factors for pancreas graft loss within 3 months postoperatively among 170 simultaneous pancreas-kidney transplantation (SPKT) we examined 38 variables. METHODS: Twenty-two variables were related to recipients; 12 to donors and 4 to the surgical procedure. In addition the latest follow-up dates as well as the transplant and/or death dates. Independent variables were examined with reference to the dependent pancreatic loss variable, excluding losses owing to deaths. Variables with statistical significance were analyzed to predict early graft loss. RESULTS: Univariate analyses determined the following significant variables: kidney cold ischemia time, older donors, non-white donors, death cause related to vascular disease, wound infection, and length of extended hospitalization. However, multivariate analysis showed that only donor age and kidney cold ischemia time were significant predictors for early pancreatic graft loss. CONCLUSION: Donor age and kidney cold ischemia time were independently related to pancreatic loss after SPKT within 3 months posttransplantation.
Subject(s)
Kidney Transplantation/physiology , Pancreas Transplantation/adverse effects , Adolescent , Adult , Age Factors , Amylases/metabolism , Analysis of Variance , Body Mass Index , Cause of Death , Creatinine/metabolism , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/surgery , Diabetic Nephropathies/surgery , Ethnicity , Female , Humans , Male , Middle Aged , Multivariate Analysis , Retrospective Studies , Risk Factors , Sodium/blood , Surgical Wound Infection/mortality , Tissue Donors/statistics & numerical data , Treatment Outcome , Vascular Diseases/mortalityABSTRACT
Substitution of cyclosporin with tacrolimus should be considered for paediatric liver transplant recipients with cyclosporin-associated complications such as hypertension, gum hyperplasia, hirsutism, gynaecomastia and growth retardation, as well as recurrent or refractory acute rejection, chronic duct injury or chronic rejection. Continued experience with well tolerated drug administration and careful monitoring during drug substitution has limited drug toxicity associated with tacrolimus to a level comparable to or less than that associated with cyclosporin. Successful outcome with long term graft salvage has been reported in up to 80% of patients converted to tacrolimus because of acute rejection and 50% of patients converted because of chronic rejection. Nearly all children converted because of cyclosporin-related complications have a successful outcome. Additional benefits of conversion to tacrolimus include improvement in growth and resolution of hypertension, hirsutism and cushingoid facies. Complete corticosteroid withdrawal is possible in up to 78% of children post-conversion. Long term outcome in these patients may be optimised by conversion to tacrolimus at an early stage of acute or chronic transplant rejection in order to minimise the cumulative amount of immunosuppression. Avoidance of cyclosporin-related toxicity and minimisation of corticosteroid therapy may further improve patient compliance to drug therapy.
Subject(s)
Cyclosporine/therapeutic use , Immunosuppressive Agents/therapeutic use , Liver Transplantation/immunology , Tacrolimus/therapeutic use , Child , Cyclosporine/adverse effects , Graft Rejection/drug therapy , Humans , Immunosuppression Therapy/methods , Immunosuppressive Agents/adverse effects , Lymphoproliferative Disorders/drug therapy , Postoperative Complications/drug therapyABSTRACT
The current management of hepatic allograft rejection after liver transplantation in children requires effective baseline immunosuppression to prevent rejection and rapid diagnosis and treatment to manage acute rejection episodes. The subsequent impact on chronic rejection is dependent on the combination of adequate prevention and the treatment of acute rejection. Tacrolimus is a macrolide lactone that inhibits the signal transduction of interleukin-2 (IL-2) via calcineurin inhibition. Introduced in 1989, tacrolimus was first used in the salvage of refractory acute or chronic rejection under cyclosporin or to rescue patients with significant cyclosporin-related complications. The majority of paediatric transplant centres use a combination of steroids with tacrolimus as a basic immunosuppressant regimen following paediatric liver transplantation. This combination has allowed the acute cellular rejection-free rate to increase to between 30 and 60%, while lowering the rate of refractory rejection to less than 5%. Corticosteroid-resistant rejection is commonly treated with monoclonal (muromonab CD3) or polyclonal preparations. Although most episodes of acute cellular rejection occur during the first 6 weeks after liver transplant, the appearance of late acute liver allograft rejection must raise the question of noncompliance, especially in the adolescent population. Chronic rejection is becoming increasingly rare under tacrolimus-based immunosuppression. Tacrolimus is effective in reversing refractory acute cellular rejection or early chronic rejection in patients initially treated with cyclosporin-based regimens. Patients with a history of noncompliance as well as children with autoimmune liver disease are at risk of chronic rejection. Retransplantation therapy for chronic rejection has, fortunately, become more rare in the tacrolimus era with only 3% of retransplants being performed for this indication. Newer immunosuppressive agents are further modifying the long term management of liver allograft rejection. These include mycophenolate mofetil, rapamycin and IL-2 antibodies such as daclizumab. The development of these agents is allowing patient-specific immunosuppressive management to minimise rejection as well as the complications related to immunosuppression.
