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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