Organ Transplant Complications and Rejection

Table of Contents

Types of Transplant Rejection

TypeTimeMechanismPathologyHypersensitivityManagement
Host against Graft (Host vs Graft)Mnemonic: TIA
HyperacuteImmediate (<5 days)Anti-donor antibodies in recipientThrombosis and Obliteration of blood supplyType IIUntreatable
Prevent by cross-matching
Remove graft
Acute (most common)< 6 months (most common in 1st month)Anti-donor T cell proliferation in recipientInterstitial lymphocyte infiltrateType IVPrevent/reverse with immunosuppressants
ChronicMonths to years (usually >6 months)Development of multiple cellular and humoral immune reactions to donor vasculatureArteriosclerosis and intimal fibrosisType III and IVUnresponsive to immunosuppressants
Accelerated acuteFirst few days (7-10 days)Activation of memory T and/or B lymphocytes in pre-sensitized receipients (post-formed CMI and antibodies)May be responsive to antibody therapy: OKT3, ATG
Graft vs Host Disease (GVHD) is opposite of transplant rejection (i.e., graft against host). It is the reaction of donor immune cells in transplanted graft to host cells in immunocompromised patients. It is a type IV hypersensitivity reaction and frequently occurs in bone marrow and liver transplant (rich in lymphocytes).
heart transplant

Post-renal transplant fluid collections

Mnemonic: HEAL

1. Hematoma (Immediate)

2. Encapsulated urine collections/urinomas (1-2 weeks): commonest cause is ureter tip necrosis and may require revision anastomosis

3. Abscess (3-4 weeks)

4. Lymphocele (2 months)

Post-renal transplant renal injury

Mnemonic: SCRI

1. Structural causes: USG

  • Renal artery thrombosis – Sudden complete loss of urine output (T/t: Immediate surgery within 30 minutes)
  • Renal artery stenosis – Uncontrolled hypertension; allograft dysfunction and edema (T/t: Angioplasty)
  • Renal vein thrombosis – Pain and swelling of graft site, hematuria and oliguria (Graft is usually lost)

2. Calcineurin inhibitor toxicity: Cyclosporin level

3. Rejection and/or Recurrence of primary disease: Biopsy (rejection type; MCGN>IgA nephropathy>FSGS)

4. Infection: PCR

  • 1-6 months post-transplant: BK virus, CMV
  • >6 months post-transplant: PTLD (Post-transplant lymphoproliferative disorder) – EBV

Outcomes

Transplant1 year survival5 year survival
Renal90%65%
Cardiac80%65%
Hepatic80%55%
Lung70%55%
Pancreatic75%
Small bowel60%

Immunosuppressants

DrugsMechanismAdverse effects
CorticosteroidsSuppress all inflammatory elements of immune response‘Cushingoid’ effects
Calcineurin inhibitors (Cyclosporin, Tacrolimus)Suppress T-cells and inhibit IL-2 releaseNephrotoxicity (more with cyclosporin)
Diabetes (with tacrolimus)
Anti-proliferatives (methotrexate, azathioprine, mycophenolate)Prevent cell mediated cell mitosis and amplification of responseRenal and hepatic dysfunction, marrow suppression
mTOR inhibitors (sirolimus, rapamycin, everolimus)Prevents T cell and B cell activation by blocking IL-2 receptorsInterstitial pneumonitis
Biologic effectorsBasiliximab: anti-IL2-receptor antibody
Rituximab: anti-CD20 antibody
Cytokine release syndrome
Hydroxychloroquine (for chronic GVHD)Inhibits antigen processingVisual disturbances
Thalidomide (for chronic GVHD)Inhibits T-cell function and migrationSedation, constipation, teratogenicity


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