Induction Therapy: A Modern Review of Kidney Transplantation Agents

Kidney transplantation remains the most effective modality for the treatment of end-stage renal disease. The development of induction therapy has significantly reduced the incidence of acute rejection within the first six months following kidney transplantation. As a result, induction therapy is typically administered in the majority of kidney transplants. Moreover, early graft function has also improved with the advent and routine administration of induction therapy. Effective induction therapy has also expanded the donor pool as it allows for more effective utilization of marginal donor kidneys including expanded criteria donors and donors after cardiac death. It may also benefit higher immunologic risk recipients such as highly sensitized, African American, and repeat transplant patients. Polyand monoclonal antibody agents are available for use as induction agents, including rabbit Anti-thymocyte globulin, interleukin-2 receptor antagonists, and alemtuzumab each of which have proven efficacy but have discrete advantages and disadvantages. Tailoring induction therapy to individual patient profiles provides the best opportunity for both short and long-term outcomes of the patient and allograft. Moreover, we explore the role of induction therapy with long-term steroid avoidance immunosuppression regimens in modern kidney transplantation. Overall, we review the safety and efficacy of this important group of induction agents and discuss an approach to tailoring their use for specific patients undergoing kidney transplantation. *Corresponding author: Cheguevara Afaneh, MD, Department of Surgery, Weill Cornell Medical College, New York Presbyterian Hospital, 525 East 68th Street, Box 44, Tel. 212-746-5330; Fax: 212-746-6890; E-mail: [email protected] Received November 08, 2011; Accepted December 16, 2011; Published December 20, 2011 Citation: Afaneh C, Aull MJ, Schubl S, Leeser DB, Kapur S (2011) Induction Therapy: A Modern Review of Kidney Transplantation Agents. J Transplant Technol Res S4:001. doi:10.4172/2161-0991.S4-001 Copyright: © 2011 Ferchichi H, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Introduction Historically, acute rejection episodes were most prevalent in the early postoperative period. Prior to induction therapy, kidney transplantation was plagued with high rates of acute rejection. Early attempts at preventing acute rejection consisted only of glucocorticoids and azathioprine. However, advancements in the understanding of kidney transplantation immunology lead to the development of “induction therapy.” Induction therapy refers to any potent immunosuppressive agent administered in the perioperative period to prevent episodes of acute rejection and immunologically-mediated causes of graft loss. The widespread use of these agents has significantly decreased the incidence of acute rejection in the first six months; however, long-term allograft survival has not yet been prolonged by the agents used in modern kidney transplantation [1]. In 1995 induction therapy was used in less than half of all kidney transplants in the United States, a decade later, approximately 70% of all kidney transplant recipients received induction therapy [2]. Induction therapy carries various risks, the most serious of which is overimmunosuppression resulting in infection or malignancy [3,4]. Appropriate selection and dosing of induction therapy can prevent acute rejection episodes, postpone the onset of acute rejection outside the critical perioperative period, potentially decrease the degree of ischemia-reperfusion injury, and graft function [5,6]. The latter has become increasingly important as major transplant centers continue to utilize marginal donor kidneys, including expanded criteria donors (ECD) and donation after cardiac death (DCD) donors. Additionally, induction therapy has benefited patients at higher risk of acute rejection, including those that are highly sensitized, African American, or undergoing retransplantation [7,8]. Nevertheless, despite the decrease in acute rejection episodes and improvement in early graft function, overall allograft survival has not been clearly shown to improve with induction therapy. Induction therapy commonly refers to antibodies against specific or non-specific antigens on targeted immune cells (Table 1). These can be classified as lymphocyte depleting agents and non-lymphocyte depleting agents. The categorization is based on the ability of the therapeutic agent to target specific antigens or cells, leading to a decrease in the total cellular expression or reduction in cell counts. Most depleting agents are relatively potent with potential for toxicity with prolonged administration (i.e. OKT3). On the other hand, nondepleting agents are generally well-tolerated with reasonable side effect profiles, yet are less potent (i.e. anti-interleukin-2 receptor antibody). Depleting agents are also used for severe or refractory cases of acute rejection and have proven to be more effective than glucocorticoids in treating these episodes of acute rejection [9]. Polyclonal antibodies are typically heterogeneous, with batch-to-batch variability, variable invivo reactions, typically require larger doses, and are less susceptible to immune elimination (Figure 1). Monoclonal antibodies are more consistent, predictable, and require smaller doses. Murine monoclonal antibodies are susceptible to immune elimination, but chimeric (e.g. basiliximab) and especially humanized (e.g. alemtuzumab, daclizumab) antibodies are less susceptible to immune elimination. Some major institutions have modified their immunosuppression regimen to avoid long-term steroid maintenance. These regimens have utilized more potent induction agents (i.e. rabbit Antithymocyte globulin [rATG]) even in higher risk patients, such as the elderly or patients with multiple co-morbidities. The armamentarium of induction agents in modern transplantation has expanded, leading to the clinical dilemma in selecting the most appropriate agent for a given patient while taking into account co-morbidities, donor quality, immunological status, and planned maintenance therapy. The importance of induction therapy compared to transplantation without induction therapy has been clearly demonstrated and routinely accepted. The following review focuses on the three most commonly used induction agents in modern kidney transplantation, including rATG, basiliximab, and alemtuzumab. The advantages Citation: Afaneh C, Aull MJ, Schubl S, Leeser DB, Kapur S (2011) Induction Therapy: A Modern Review of Kidney Transplantation Agents. J Transplant Technol Res S4:001. doi:10.4172/2161-0991.S4-001