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Organ Transplantation Education

Organ transplantation constitutes the transfer of organs, tissues or human cells from a healthy person (donor) to an individual with a damaged or failing organ (recipient), in order to maintain normal physiologic function.1


History
References about organ transplantation are found in medical literature as early as 800 BC with the first documented solid organ transplant occurring in the early 1900s. Since then, advances in surgical techniques, tissue typing, and immunosuppressive drug therapy have improved the success rates of organ transplantation.


Types of Transplant1
Transplants can be broadly categorized into the following:

  • Autograft: transfer of tissue from and to the same person
  • Allograft: transfer between two genetically non-identical members of the same species
    - Allogeneic transplant: the donor is a genetically matched person, usually a family member
    - Matched unrelated transplant: type of allogeneic transplant, where the donor is not a family member
  • Syngraft: transfer of tissues or organs from an identical twin
  • Xenograft: transfer of tissues or organs across species


Based on the placement of grafts, the process can be described as:

  • Orthotopic transplantation: grafts placed in normal anatomic position to replace the diseased native organ (liver or heart transplantation)
  • Heterotopic transplantation: grafts placed in a non-anatomic location where the native organ is left in place (kidney transplantation)

Transplant Rejection
A very real concern in organ transplantation is the possibility of transplant rejection. Rejection is a complex response to the transplanted tissue and involves several components of the immune system, such as lymphocytes, cytokines, and macrophages, which recognize the transplanted organ as a foreign substance and try to eliminate it from the body. The immune response subsequently leads to local inflammatory injury and graft damage.1

Depending on the time of onset and pathogenesis, rejection can be classified into 3 distinct categories:

Hyperacute rejection

  • Occurs within minutes to hours following the reperfusion of the transplanted organ or tissue
  • Caused by humoral immune response
  • Leads to immediate thrombotic occlusion and loss of the transplanted tissue

Acute rejection

  • Cell-mediated process
  • Most common type of rejection
  • Occurs within a few days to months after transplantation
  • Incidence of this type of rejection has reduced considerably with the advent of modern immunosuppressive drugs

Chronic rejection

  • Occurs over months to years
  • Involves both immune and non-immune mechanisms that lead to a slow deterioration of graft function
  • Increasingly more common since the use of immunosuppressive drugs has enhanced the short-time survival rate of grafts

A key element in preventing organ rejection is the use of immunosuppressant drugs (ISDs). ISDs can be administered as a countermeasure to suppress the host’s immune response. However, regular monitoring of immunosuppressant drug concentrations is imperative to prevent infections and malignancies that occur as a result of the suppressed immune system. In addition, ISD monitoring is essential to maintain the balance between the appropriate therapeutic drug levels necessary to prevent organ rejection with the potential toxic side effects that accompany ISD therapy.

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Pre- and Post-transplant Monitoring
To optimize transplantation outcomes, regular monitoring of various pre- and post-transplant factors is vital. Some of the routine monitoring tests conducted include the following:

Routine pre- and post-transplant tests: Complete blood count, chemistry screening panel, blood pressure, echocardiogram, electrocardiogram (ECG), mammogram, bronchoscopy, pulmonary function test (PFT), ultrasonography and biopsies

Pre- and post-transplant serological screening for infectious diseases: Human immunodeficiency virus (HIV), hepatitis A, B, and C viruses, cytomegalovirus (CMV), herpes simplex virus, Epstein-Barr virus (EBV), toxoplasmosis, and varicella-zoster virus and measles virus (in pediatric patients)

Monitoring for organ function: Tests for monitoring toxic side effects of immunosuppressive drugs and the graft function for some of the organs include:

  • Kidney: cystatin C, urinary proteins, creatinine, and blood urea nitrogen (BUN)
  • Heart: troponin I, creatine kinase muscle-brain fraction isoenzyme (CK-MB), high sensitivity C-reactive protein (hsCRP), lipid profile, and apolipoproteins
  • Liver: liver enzymes, albumin, protein C, and prothrombin time (PT)
  • Pancreas: glycosylated hemoglobin (HbA1c), glucose, lipase, amylase, and urinalysis


Early detection of acute phase reactions and complications: hsCRP, serum amyloid A protein (SAA), and cystatin C are monitored.

Investigations for preventing transplant rejection:

  • Human leukocyte antigen system (HLA) typing
  • Anti-HLA antibody screening and C4d staining
  • Donor-recipient cross matching

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Reference
1. Cuschieri A, et al. Clinical Surgery. 2003:759. Link