Induction therapy in pediatric renal transplant recipients: an overview

Abstract

Induction therapy to prevent the acute rejection of mismatched allografts with the ultimate aim of prolonging the life of the allograft has been the cornerstone of immunosuppression since the introduction of renal transplantation. Agents used for induction therapy have changed over time. Their role in transplantation is expanding to include corticosteroid avoidance and immunosuppression minimization. This review provides an overview of induction therapies for renal transplantation including historic therapies such as total lymphoid irradiation and Minnesota antilymphocyte globulin, and current therapies with polyclonal and monoclonal antibodies and chemical agents, with special emphasis on children. Data from adult studies, and pediatric studies whenever available, are summarized. A brief summary of experimental therapies with fingolimod and belatacept is provided. Historically, induction therapies were targeted at T cells. The role of induction therapies targeted at B cells is emerging in select groups of patients that include highly sensitized recipients and those receiving transplants from blood group incompatible donors. With the advent of newer maintenance immunosuppressive medications and with very low rates of acute rejection, induction protocols for renal transplantation need to be targeted so that excessive immunosuppression and infections are avoided. Several single-center and registry data analyses in children suggest that the addition of an interleukin (IL)-2 receptor antagonist may improve graft survival compared with no induction. The safety profile of IL-2 receptor antagonists is indistinguishable from that of placebo, with no apparent difference in the incidence of infection or post-transplant lymphoproliferative disease. IL-2 receptor antagonists and polyclonal lymphocyte-depleting antibodies offer equivalent efficacy in standard-risk populations. However, in high-risk patients, acute rejection rates and graft outcomes may be improved with the use of lymphocyte-depleting agents such as Thymoglobulin. However, cytomegalovirus infection and other infections may be more common with this therapy. Therefore, in patients at high risk of graft loss, Thymoglobulin may be the preferred choice for induction therapy, while for all other patients, IL-2 receptor antagonists should be considered the first-line choice for induction therapy. Newer lymphocyte-depleting agents such as alemtuzumab may be better utilized in minimization regimens involving one or two oral maintenance immunosuppressive agents.