IMMUNONUTRITION AND TRANSPLANT SUCCESS

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While improvements in immunosuppression have increased the short term survival of renal allografts, the rate of loss after the first six months has changed insignificantly during the past three decades. The long-term objective of this proposal is to develop nutritional supplements that will decrease complications and allow improved long lasting allograft survival in man with minimal immunosuppression. The specific aim of this study is to perform a prospective, randomized clinical trial in patients receiving renal allografts to determine the tolerance, safety, and efficacy of a special transplant dietary supplement. Recent animal studies have shown that both arginine and canola oil, which contains both omega 3 and omega 9 fatty acids, will remarkedly prolong allograft survival when given with a short course of cyclosporine A. An ongoing study in stable posttransplant patients has shown that dietary supplementation with arginine and canola oil will improve allograft function as measured by a decrease in serum creatinine and an improvement in creatinine clearance. This supplement has also reduced responsiveness in mixed lymphocyte cultures and has caused a shift in the cytokine production from a Th1 to Th2 type response. There have been no significant adverse effects from administration of a combination of arginine and canola oil for up to 18 days. The proposed study will randomly assign patients receiving a new renal allograft into study and control groups which will receive the same chemical immunosuppression. The study group will begin dietary supplements of arginine and canola oil at transplant. Major endpoints of the study will include incidence of rejections, type and severity of rejection, time to first rejection, renal function, patient and graft survival, incidence of cardiovascular events, incidence and length of initial and rehospitalization, incidence and types of infections, incidence of chronic rejection, and effect on blood pressure. It is anticipated that each of these major endpoints will be influenced positively and that nutritional immune modulation will become an important component of therapeutic strategies to induce long-term tolerance in solid organ transplantation.