The long-term objective of our Project is to determine whether posttransplant immune parameters can predict which solid organ transplant recipients will tolerate decreased immunosuppression.
The specific aims for recipients developing donor antigen-specific hyporesponsiveness. 1. To determine, in a prospective randomized trial, whether kidney transplant recipients can be tapered off steroids without an increased incidence of late acute rejection or of chronic rejection. 2. To determine whether heart transplant recipients can be tapered off steroids without an increased incidence of acute rejection and without an increased risk of allograft vasculopathy. 3. To determine whether lung transplant recipients can be converted from oral to inhaled steroids without an increased incidence of acute rejection episodes and without an increased risk of obliterative bronchiolitis. It is well-recognized that posttransplant immunosuppression is associated with morbidity. And many immunosuppressive care protocols attempt to lower or withdraw some immunosuppressive agents. However, trials of immunosuppression drug withdrawal or dosage lowering, based on clinical criteria alone, have not been routinely successful. We have previously shown that patients who develop donor antigen-specific hyporesponsiveness have decreased incidence of late acute rejection episodes, decreased chronic rejections (biopsy proven in kidney transplant recipients, coronary artery disease on angiogram in heart transplant recipients, and of obliterative bronchiolitis in lung transplant recipients), and improved long term graft survival. The goal of the current study is to determine whether those who have developed donor antigen-specific hyporesponsiveness can have the same excellent long-term outcome after prednisone withdrawal ( in kidneys and heart recipients) or conversion to nebulized prednisone (in lung transplant recipients). Identification of a subpopulation of patients who can safely tolerate prednisone (in long transplant recipients). Identification of a subpopulation of patient who can safely tolerate prednisone withdrawal will allow potential for decreased morbidity for these, while simultaneously not withdrawing prednisone from those who would be at risk for rejection episodes, will similarly help preserve graft function and decrease morbidity (due to the antirejection treatment). Finally, for lung transplant recipients who remain responsive to donor antigens, we will also determine if the addition of inhaled steroids to their oral steroid regimen will decrease the risk of bronciolitis obliterans. Thus, this study has the potential for allowing selective immunosuppression for transplant recipients after the first year. The selective immunosuppression will help improve graft survival while potential decreasing posttransplant morbidity.
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