Study Objective: The objective of this study is to evaluate the ability of arginine and Coromega(r) (a source of Omega-3 fatty acids) dietary supplements to modulate the alloimmune response and cardiovascular risk in African American kidney transplant recipients. Over the last 20 years, significant improvements have occurred in graft and patient survival following kidney transplantation. However, outcomes in African American patients continue to lag behind those of other ethnic and racial groups. Genetic predisposition to heightened alloimmunity, and to cardiovascular disease, accounts in part for the poor transplant outcomes in this patient population. The dietary supplements arginine and the Omega-3 fatty acids have been shown to have both immunomodulatory and beneficial cardiovascular effects in the general population, and in patients with renal disease. There is promising preliminary evidence that, together with optimal immunosuppressive therapy, nutritional supplementation with arginine and Omega-3 fatty acids has the potential to reduce the burden of acute rejection and cardiovascular risk following transplantation in African American recipients. The current application outlines a plan to develop a phase 3, prospective, randomized, placebo-controlled, multicenter clinical trial to formally test the hypothesis that nutritional supplementation can improve acute rejection and cardiovascular risk among African American kidney transplant patients. Adult African American women and men, 18-65 years of age, will be enrolled to the study following informed consent. The immunosuppressive regimen will be finalized over the course of the R34 grant period. Patients in the study arm will receive the nutritional supplements arginine and (Omega-3) fatty acids; patients in the control arm will receive a placebo. Objectives at 1 year post transplant will include an assessment of the incidence of acute cellular rejection. The development of allograft interstitial fibrosis and tubular atrophy (chronic allograft nephropathy), as well as the incidence of cardiovascular events, the evolution of cardiovascular risk factors, and both patient and graft survival will be monitored over five years. The long-term objective of the proposed research is to improve the graft and patient survival of African American recipients of kidney transplants through nutritional supplementation of the immunosuppressive regimen. ? ? ?
