What is the management of acute antibody-mediated rejection?

Management of Acute Antibody-Mediated Rejection

The management of acute antibody-mediated rejection (AMR) requires a combination of plasma exchange, high-dose corticosteroids, and immunomodulatory therapies to remove circulating antibodies and suppress the immune response. 1

First-Line Treatment Strategy

Immediate Interventions

• High-dose corticosteroids: Methylprednisolone 1g IV daily for 3 consecutive days 1
• Plasma exchange: Exchange twice the blood volume with fresh-frozen plasma daily for 5-7 days 1
  • For patients <8kg: Exchange transfusions instead of plasmapheresis
  • For patients >8kg: Standard plasmapheresis

Baseline Immunosuppression Modifications

• Replace cyclosporine with tacrolimus 1
• Consider substituting mycophenolate mofetil (MMF) or cyclophosphamide for azathioprine 1

Second-Line Therapies

For Persistent or Severe AMR

• Intravenous immunoglobulin (IVIg): 1-2 g/kg in divided doses 1

  • Mechanism: Blocks Fc-γ receptors, inhibits complement system, neutralizes antibodies
  • Typically administered after completion of plasma exchange course

• Rituximab: 375 mg/m² IV (for targeting B cells) 1

  • Consider weekly administration for up to 4 weeks
  • For pediatric patients with body surface area <0.5 m², use 12.5 mg/kg

For Refractory Cases

• Bortezomib: 1.3 mg/m² on days 1,4,8, and 11 (targets plasma cells) 1
• Anti-thymocyte globulin (ATG): 1.5 mg/kg daily for 3-7 days (for severe hemodynamic compromise) 1
• Eculizumab: For complement-mediated severe cases 2

Treatment Based on AMR Severity

pAMR1 (Subclinical)

• Increase maintenance immunosuppression
• Consider single dose of methylprednisolone 500mg IV

pAMR2 without Dysfunction or DSA

• Pulse steroids only: Methylprednisolone 500mg-1g IV daily for 3 days 3

pAMR2 with Dysfunction and/or DSA

• Steroids plus additional therapies (IVIg, plasmapheresis, rituximab) 3

pAMR3 (Severe Rejection)

• High-dose steroids with multiple additional therapies 3
• Consider ATG if hemodynamically compromised
• Mechanical circulatory support may be required in cases of cardiogenic shock 1

Monitoring and Follow-up

• Monitor donor-specific antibody (DSA) levels before and after treatment 1
• Perform follow-up endomyocardial biopsies to assess treatment response
• Echocardiography to evaluate graft function

Special Considerations

Pediatric Patients

• Weight-based dosing with careful attention to maximum doses 1
• Exchange transfusions rather than plasmapheresis for patients <8kg

Hemodynamic Compromise

• More aggressive approach with combination therapy
• Early consideration of mechanical circulatory support
• Anti-thymocyte globulin 1.5 mg/kg daily for 3-7 days 1

Pitfalls and Caveats

• Plasma exchange alone is insufficient; must be combined with other immunomodulatory therapies 1
• Rebound antibody production can occur after plasma exchange
• Risk of bleeding complications with plasma exchange requires monitoring of coagulation parameters
• IVIg has high risk of recurrence when used alone 1
• Long-term corticosteroid use can lead to hypertension, diabetes, and osteoporosis 3
• Retransplantation may be the only option for patients who do not respond to aggressive measures, but carries lower survival rates than primary transplantation 1

Emerging Therapies

• Anti-CD38 therapy for targeting long-lived plasma cells (particularly in late AMR) 2
• Complement inhibitors for severe or refractory cases 2

The management of AMR requires prompt diagnosis and aggressive treatment to prevent graft loss. While there is no consensus on the optimal treatment regimen, the combination of plasma exchange, high-dose corticosteroids, and targeted immunomodulatory therapies has shown efficacy in most cases 1.