Treatment of Antibody-Mediated Rejection (ABMR) Post Kidney Transplant

First-Line Treatment Protocol

The American College of Cardiology recommends initiating combination therapy with plasmapheresis, intravenous immunoglobulin (IVIG), and high-dose corticosteroids as first-line treatment for acute ABMR in kidney transplant recipients, with rituximab added for refractory cases and bortezomib reserved for severe or treatment-resistant rejection 1, 2, 3
Corticosteroid pulse therapy remains the foundation of ABMR treatment, typically administered as methylprednisolone 250-1000 mg IV for 3 days, targeting nuclear factor-κB and activator protein-1 pathways to suppress immune activation 1, 2, 3
Plasmapheresis should be initiated to physically remove circulating donor-specific antibodies (DSAs), typically performed 1-7 sessions per week for 1-4 weekly cycles, exchanging 1-2 plasma volumes per session 1, 3
IVIG administration at 1-2 g/kg divided over 2-4 doses works through multiple mechanisms: blockade of Fc-γ receptors, complement inhibition, neutralization of circulating antibodies, and downregulation of B-cell receptors 2, 3, 4

Ensure adequate mycophenolate mofetil (MMF) is part of the maintenance regimen, as MMF reduces B-cell proliferation and antibody production, with demonstrated reduction in both anti-HLA and non-HLA antibodies in kidney transplant recipients 5, 6, 7

Bortezomib (proteasome inhibitor) is indicated for severe or refractory ABMR, administered at 1.3 mg/m² on days 1, 4, 8, and 11, and uniquely targets plasma cells—the actual antibody-producing cells that rituximab cannot reach 8, 9

Eculizumab (C5 complement inhibitor) may be considered for severe, life-threatening ABMR refractory to standard therapies, though it is not FDA-approved for this indication and cost/insurance coverage is prohibitive 5, 6, 10, 7
Daratumumab (anti-CD38 monoclonal antibody) represents a newer option for refractory cases, targeting CD38-expressing plasma cells and NK cells that produce DSAs, and the American Heart Association recognizes daratumumab as reasonable secondary therapy (Class IIa; Level of Evidence C) 9

Do not use total lymphoid irradiation (TLI) due to potential long-term complications including myelodysplasia and acute myelogenous leukemia, with unclear efficacy for ABMR 11
Splenectomy should not be performed except as an absolute last resort after all other therapies have failed, given conflicting reports of death and infectious complications in kidney transplant recipients 11
Cyclophosphamide has only modest data supporting its use and is generally reserved for combination therapy in highly refractory cases, not as monotherapy 5, 6, 10

Monitor DSA levels serially to assess treatment response, as reduction in DSA titers correlates with treatment success, and perform follow-up kidney biopsies to document histologic response and guide therapy duration 8, 4, 9