**1. Introduction**

The use of potent induction agents and maintenance immunosuppression has substantially decreased the risk of acute rejection. One year graft survival is greater than 92% in deceased donor and 96% in living donor transplant recipients with current immunosuppressive strategies according to the Scientific Registry of Transplant Recipients, (SRTR, 2009).

Half life appears to be the best way to give the patient a general understanding of how long their transplant may last. The graft half life for deceased donor transplants has increased from 6.6 years in 1989 to 8.8 years by 2005. Significant progress has also been made in high risk transplants where graft half life has improved from 3 years in 1989 to 6.4 years in 2005 for expanded criteria donor recipients. For the standard low risk patient receiving a living donor kidney, current immunosuppression should guarantee a graft half life of at least 11.9 years. [1]

However, the problems of chronic rejection and chronic allograft dysfunction still remain, often leading to graft loss and shortened long-term graft survival.[2] The 5 and 10 year adjusted graft survival for deceased donor transplants were 70% and 43% respectively. The adjusted 5 year and 10 year graft survival for living donor transplant were 82% and 60% respectively. (SRTR, 2009)

Humoral rejection and sensitized patients continue to be a clinical challenge. The management and clinical impact of subclinical rejection also remains unclear. Although there are numerous clinical trials testing different immunosuppressive strategies, a lack of large prospective randomized clinical trials has decreased our ability to generate consensus on the best immu‐ nosuppressive strategies for preserving long-term allograft function. This chapter will focus on reviewing multiple aspects of immunosuppressive therapy, such as; 1) mechanism of action, 2) how therapies are being utilized in practice, 3) the advantages and/or disadvantages

© 2013 Ghanta et al.; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2013 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

of different therapies and 4) major clinical trials evaluating the effectiveness of specific regimens. New emerging strategies and therapeutic agents that are being investigated will also be discussed.

opportunistic infections and lymphoma. Patients are typically prophylaxed for cytomegalo‐

Overview of Immunosuppression in Renal Transplantation

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Alemtuzumab or Campath is a recombinant humanized monoclonal antibody directed against CD52. It binds to CD52 receptor on the surface of T and B lymphocytes leading to antibody mediated cell lysis. CD52 is present on virtually all B and T cells as well as macrophages, NK cells and some granulocytes. It was initially approved for use in B-cell lymphocytic leukemia and is now used in transplantation. Alemtuzumab induces a rapid and profound depletion of peripheral and central lymphoid cells. It is typically administered as a single 30 mg dose either subcutaneously or intravenously. Just like rATG patients receive premedication to prevent infusion reactions. When used as an induction agent it is given intraoperatively. Single dose administration makes Campath a more convenient option to administer compared to rATG

Potential side effects include thrombocytopenia, vomiting, diarrhea, headache and rarely autoimmune hemolytic anemia. Infection and lymphoma risk is similar to rATG, and patients are

IL-2 receptor blockers, Basiliximab (Simulect) and daclizumab (Zenapax) are humanized anti-CD25 monoclonal antibody preparations. They are targeted against the α-chain (CD25) of the IL-2 receptor. Rather than working by lymphocyte depletion, these agents block IL-2 signaling which is required for T-cell growth, differentiation and expansion. Because both agents are derived from mice and partly humanized, they cause far less infusion reactions compared to rATG. Daclizumab is currently not available for use in United States. Basiliximab is used in the U.S. and is typically administered as 20mg intravenous infusion intraoperatively with subsequent doses given on the third or fourth post operative day. Neither drug has major side effects. Risk of infection and lymphoma is far less than that of lymphocyte depleting agents.

According to the annual report from SRTR 2009, 83% of transplant recipients received induction agents at the time of kidney transplant. The majority of patients received a T-cell

How agents are used in practice is dependent on a number of factors which range from center specific protocols to tailored immunosuppression based on recipient factors. The risks and benefits of each agent must be assessed in every patient individually based on the individuals' immunologic risk and susceptibility to infectious complications. Induction agents clearly

depleting agent, 58%, and 21.2% received an IL-2 receptor blocking agent.

virus infection and pneumocystis carinii infection post rATG administration.

which is typically administered daily for 3-5 days.

similarly prophylaxed for potential infections.

**2.3. IL-2 receptor blockers (IL-2RA)**

**3. Which induction agent?**

**2.2. Alemtuzumab**

*2.2.1. Side effects*
