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Content Update

May 26, 2020

Expanding the Donor Pool in Solid Organ Transplantation: The landscape of solid organ transplantation has changed based on organ allocation and a larger number of candidates on waiting lists. Transplant centers are expanding use of nontraditional donors to aid in access to transplantation. This changes the appropriate transplant immunosuppression and post-transplant monitoring and often dictates additional medication such as antivirals. Pharmacotherapy decisions are often complicated by prolonged organ dysfunction, specifically liver and kidney. This update focuses on four different scenarios and their implications, namely the use of donors who are: (1) older; (2) donate after cardiac death; (3) living, specifically for liver donation; and (4) Hepatitis C antibody positive.

LEARNING OBJECTIVES

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 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 currently available immunosuppressive agents in terms of mechanisms of action, adverse events, and drug–drug interactions (DDI).

  8. Develop a therapeutic drug-monitoring plan to assess effectiveness of the immunosuppressive drugs.

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

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

INTRODUCTION

The earliest recorded attempts at organ transplant date back thousands of years.1 More than a few apocryphal descriptions exist from ancient Egypt, China, India, and Rome describing experimentation with transplantation. However, it was not until the early 1900s that French surgeon, Alexis Carrel, pioneered the art of surgical techniques for transplantation.1 Together with Charles Guthrie, Carrel experimented in artery and vein transplantation. Using revolutionary methods in anastomosis operations and suturing techniques, Carrel laid the groundwork for modern transplant surgery. He was one of the first to identify the dilemma of rejection, an issue that remained insurmountable for nearly half a century.1

Prior to the work of Alexis Carrel, malnourishment was the prevailing theory regarding the mechanism of allograft rejection.1 However, in 1910, Carrel noted that tissue damage in the transplanted organ was likely caused by multiple, circulating biological factors. It was not until the late 1940s with the work of Peter Medawar that transplant immunology became better understood. Medawar defined the immunologic nature of rejection using skin allografts. In addition, George Snell observed that grafts shared between inbred animals were accepted but were rejected when transplanted between animals of different strains.1...

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