Update on diagnostic and therapeutic strategies for antibody-mediated rejection in kidney transplantation

Table 7 Evidence-based comparison of acute vs chronic antibody-mediated rejection therapies

Therapy	Use in acute AMR	Use in chronic AMR	Evidence summary	KDIGO 2023 position
PP	First-line for antibody removal; often combined with IVIG	Used selectively; less effective in chronic injury	Supported by multiple case series and consensus guidelines	Recommended in acute AMR; limited role in chronic AMR
IVIG	Adjunct to PP; modulates immune response	Used in chronic AMR with DSA presence	Moderate evidence; variable dosing strategies	Supported in both acute and chronic AMR
Rituximab	Targets CD20+ B cells; used in combination with PP/IVIG	Sometimes used in chronic AMR with active inflammation	Mixed results; better efficacy in early AMR	Considered in both settings; not universally effective
Eculizumab	Complement inhibition in severe or refractory acute AMR	Not recommended for routine chronic AMR	Effective in complement-mediated AMR; high cost, limited trials	Restricted use: Only in complement-driven AMR
Bortezomib	Used in refractory acute AMR; targets plasma cells	Limited efficacy in chronic AMR; poor outcomes in late-stage fibrosis	Early studies showed promise; later trials failed to show consistent benefit[83]	Not recommended for chronic AMR; use in acute AMR remains investigational
Tocilizumab (IL-6 blocker)	Investigational; targets inflammatory cytokine pathways	Emerging therapy in chronic AMR	Phase 2/3 trials ongoing; promising results in chronic inflammation	Under evaluation; not yet standard of care
CD38 antibodies (e.g., felzartamab)	Targets long-lived plasma cells and NK cells	Promising in chronic AMR with persistent DSA	Recent trials show reversal of AMR activity	KDIGO supports further research; not yet routine
Molecular diagnostics (MMDx, dd-cfDNA, GEP)	Used to confirm and monitor acute AMR	Valuable for detecting subclinical chronic AMR	High NPV; improves diagnostic precision	Strongly recommended for both acute and chronic AMR monitoring

PP: Plasmapheresis; IVIG: Intravenous immunoglobulin; IL: Interleukin; MMDx: Molecular Microscope Diagnostic System; dd-cfDNA: Donor-derived cell-free DNA; GEP: Gene expression profiling; AMR: Antibody-mediated rejection; DSA: Donor-specific antibody; NK: Natural killer; NPV: Negative predictive value; KDIGO: Kidney Disease: Improving Global Outcomes.