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LEARNING OBJECTIVES

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LEARNING OBJECTIVES

Upon completion of the chapter, the reader will be able to:

  1. Describe the reasons for solid organ transplantation.

  2. Differentiate between the functions of cell-mediated and humoral immunity and how they relate to organ transplant.

  3. Describe the roles of the antigen-presenting cells (APCs) in initiating the immune response.

  4. Compare and contrast the types of rejection, including hyperacute, acute, chronic, and humoral rejection.

  5. Define the terms "host–graft adaptation" and "tolerance," paying close attention to their differences.

  6. Discuss the desired therapeutic outcomes and appropriate pharmacotherapy utilized to avoid allograft rejection.

  7. Compare and contrast the currently available immunosuppressive agents in terms of mechanisms of action, adverse events, and drug–drug interactions (DDIs).

  8. Design an appropriate therapeutic regimen for the management of immunosuppressive drug complications based on patient-specific information.

  9. Develop a therapeutic drug-monitoring plan to assess effectiveness and adverse events of the immunosuppressive drugs.

  10. Write appropriate patient education instructions and identify methods to improve patient adherence following transplantation.

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KEY CONCEPTS

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  • Image not available. T cells are the chief component initiating the immune response against the allograft. The activity of T cells is mediated by a complex system of pathways resulting from the presence of antigen and the release of multiple inflammatory markers known as cytokines.

  • Image not available. Antigen-presenting cells (APCs) are vital in initiation of the immune response and play a role in both direct and indirect allorecognition.

  • Image not available. The goal of pharmacotherapy in transplantation is to induce immunosuppression with a multidrug approach to target various points of the immune system with resultant long-term allograft and patient survival, while minimizing the complications of suppressing the immune system and drug toxicity.

  • Image not available. The goals of induction therapy are to improve short-term allograft and patient survival and to reduce the incidence of acute rejection in the immediate post-transplant period.

  • Image not available. The calcineurin inhibitors, cyclosporine and tacrolimus, block T-cell activation by inhibiting the production of interleukin 2 (IL-2). They are associated with significant adverse events, such as nephrotoxicity, cardiovascular disease, posttransplant diabetes, and neurotoxicity.

  • Image not available. The antiproliferatives, azathioprine and the mycophenolic acid derivatives, inhibit T-cell proliferation. Myelosuppression is the most significant adverse event associated with these agents.

  • Image not available. Sirolimus and everolimus, target of rapamycin (ToR) inhibitors, work by decreasing the ability of T cells to respond to IL-2. The major adverse events associated with these agents are decreased wound healing, hyperlipidemia, and myelosuppression. The promising effects of allowing calcineurin inhibitor withdrawal have been limited by the significant toxicity profile of the ToR inhibitors. However, interest in this drug class as an immunosuppressant currently surrounds its potential cardiovascular and skin malignancy protective properties.

  • Image not available. Corticosteroids induce a nonspecific immunosuppression. Due to their overwhelming incidence of adverse events, many practitioners attempt to use low-dose maintenance therapy or, in some cases, complete steroid withdrawal. These agents are also effective in reversing acute rejection.

  • Image not available. Belatacept is an intermittent, IV maintenance immunosuppressive agent that blocks the costimulatory pathway of T-cell activation. This agent may contribute to improved glomerular filtration rates in renal transplant recipients; however, these patients ...

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