Introduction to Solid Organ Transplantation

Organ transplantation has been the subject of ancient myths dating back to the twelfth century. The modern era of transplantation began in the early 1900s with the development of surgical techniques for constructing vascular anastomoses [ 1 ] leading to successful kidney transplantation in dogs in 1902 [ 2 ]. The fi rst series of human kidney transplants were performed in the Ukraine beginning in 1933, but each of fi ve attempted transplants failed [ 3 , 4 ]. Around the same time, Kuss et al. [ 5 ], Servelle et al. [ 6 ], and Dubost et al. [ 7 ] reported technically successful transplantation of kidney allografts in humans, placing the organs heterotopically in the iliac fossa, similar to the technique used in the modernday operation. However, all of these grafts failed over a short period of time. In 1954, Murray et al. [ 8 , 9 ] performed a kidney transplant between identical twins and achieved longterm function. During the subsequent 10 years, more than 30 kidney transplants between identical twins were performed worldwide. These early transplants between identical twins were successful because the donors and recipients were syngeneic, sharing the same immune system and thus eliminating the possibility of immunologically mediated rejection of the graft. In the 1940s, the seminal experiments of Medawar fi rst delineated the immunologic basis for allograft rejection [ 10 ] and the need for immunosuppressive therapy to achieve successful transplantation using non-syngeneic grafts. By 1963, the fi rst human liver transplantation was performed, using early forms of immunosuppression [ 11 ]. One year later, Barnard [ 12 ] performed the fi rst successful human heart transplant. Shortly thereafter, techniques were developed for clinical heart–lung [ 13 ] and pancreas [ 14 ] transplantation. Since those early days, remarkable strides have been made to increase the success of organ transplantation to prolong the lives of patients with end-stage organ disease. General advances in medical science, including improvements in surgical techniques and the development of effective antimicrobial agents, have undoubtedly played a role in this success story. However, the current success of organ transplantation has been related more directly to an improved understanding of the mechanisms of allograft rejection and the development of immunosuppressive drugs capable of preventing or treating rejection. Although transplantation offers a survival advantage and improved quality of life for most patients with end-stage organ disease, the continued disparity between the supply of allografts from deceased donors and the growing demand for these organs represents the main limiting factor in fi eld of transplantation today. In addition, while the mechanisms and treatments for acute forms of allograft rejection are well understood, our understanding of chronic forms of rejection remains limited, and organs continue to be lost from both immune and nonimmune causes. The remainder of this chapter will review the known mechanisms of allograft rejection, the drugs used to prevent and treat rejection, and current outcomes of organ transplant recipients .