Transplant Rejection

Basics

Description

Immune response to a graft's genetically dissimilar antigens resulting in rejection of the transplanted organ:
  • HLA incompatibility:
    • Most common cause of rejection
    • Rejection of solid organ transplants
  • Blood group incompatibility:
    • Much less of a risk to graft survival than HLA incompatibility
    • May result in hyperacute rejection of primarily vascularized grafts (kidney and heart)
  • 3 phases of rejection:
    • Hyperacute:
      • Immediate postoperative period
      • Antibody reaction to red cells or HLA antigens
      • Endothelial damage
      • Platelets accumulate, thrombi develop, and tissue necrosis occurs
      • Rare with careful donor–recipient matching
  • Acute:
    • Within the first 3 mo postop
    • At any time if immunosuppressant (IS) medication is stopped
    • T-cell–dependent process. Inflammatory cells infiltrate allograft, release cellular and humoral factors, destroys graft
    • Presents with constitutional symptoms and signs of transplant organ insufficiency
  • Chronic:
    • Occurs over years
    • Results in gradual organ failure

Epidemiology

Incidence and Prevalence Estimates
  • Solid organ transplants:
    • Over 30,000 organs transplanted yearly
    • Most transplanted organs: Kidney, liver, heart, lung, intestine, pancreas
    • Most common diagnosis from visit to ED: Infection, GI/GU pathology, dehydration, electrolyte, CV and pulmonary pathology, injury, rejection
    • Up to 75% require hospitalization

Etiology

  • Reduction or noncompliance with medication:
    • Multiple medication interactions with cyclosporine, tacrolimus, or sirolimus including:
      • Phenobarbital, phenytoin, carbamazepine, rifampin, isoniazid
  • Kidney transplant rejection:
    • Early rejection caused by T- and B-lymphocytes, which attack microvasculature and impair graft perfusion; volume depletion, hypotension, infection
    • Chronic rejection caused by progressive nephrosclerosis of renal vessels, infection
  • Liver transplant rejection:
    • Acute: 48% by 6 wk, 65% by 1 yr
      • Commonly follows reduction in the IS regimen
    • Chronic: <5%
      • 1 wk–6 mo MC range to experience
  • Cardiac transplant rejection:
    • Acute rejection:
      • 75–85% of patients within the first 3–6 mo due to T-cell–mediated response
    • Chronic rejection:
      • Accelerated atherosclerosis is the hallmark
      • Associated with change in IS therapy
  • Lung transplant rejection:
    • Acute rejection develops early:
      • Can occur up to 6 times in the first year
    • Chronic rejection:
      • 25–40% of patients postop
      • MCC of death in second postop year
      • Rejection caused by endothelial, vascular, and lymphocyte inflammation, recurrent acute rejection
  • Bone marrow transplant rejection:
    • Acute graft vs. host disease:
      • Immune attack of donor marrow on lung tissue
    • Chronic graft vs. host disease:
      • 25–50% of patients
    • Marrow rejection:
      • MC in patients with plastic anemia who do not receive total body radiotherapy or in patients receiving mismatched or unrelated transplants

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