Evolving Therapeutic Approaches for Treatment of Antibody-Mediated Rejection in Renal Allograft Recipients.

Antibody-mediated rejection (AMR) is now recognized as the primary cause of the decline of functional integrity and ultimately, graft failure in kidney transplants. Evolving understanding of effectors responsible for B-cell activation and plasma cell biology has led to the informed design of new therapeutics. Currently, several novel agents with varying mechanisms of action have emerged. These include imlifidase, FcRn inhibitors, anti-cytokine (IL-6/IL-6R) therapies, and plasma cell-directed therapies, especially anti-CD38s. As our understanding of critical effector pathways responsible for ARM grows, we now know that no single agent can control all facets of antibody generation and injury. The future of antibody-directed therapeutics will require protocols consisting of multiple agents positioned in a logical sequence to rapidly and durably remove pathogenic DSAs and block their re-emergence.