Recommended Treatment for Antibody-mediated Rejection After Kidney Transplantation: The 2019 Expert Consensus From the Transplantion Society Working Group

Abstract

With the development of modern solid-phase assays to detect anti-HLA antibodies and a more precise histological classification, the diagnosis of antibody-mediated rejection (AMR) has become more common and is a major cause of kidney graft loss. Currently, there are no approved therapies and treatment guidelines are based on low-level evidence. The number of prospective randomized trials for the treatment of AMR is small, and the lack of an accepted common standard for care has been an impediment to the development of new therapies. To help alleviate this, The Transplantation Society convened a meeting of international experts to develop a consensus as to what is appropriate treatment for active and chronic active AMR. The aim was to reach a consensus for standard of care treatment against which new therapies could be evaluated. At the meeting, the underlying biology of AMR, the criteria for diagnosis, the clinical phenotypes, and outcomes were discussed. The evidence for different treatments was reviewed, and a consensus for what is acceptable standard of care for the treatment of active and chronic active AMR was presented. While it was agreed that the aims of treatment are to preserve renal function, reduce histological injury, and reduce the titer of donor-specific antibody, there was no conclusive evidence to support any specific therapy. As a result, the treatment recommendations are largely based on expert opinion. It is acknowledged that properly conducted and powered clinical trials of biologically plausible agents are urgently needed to improve patient outcomes.

FIGURE 1. Kinetics of memory B cells and plasma cell generation relative to the germinal center (GC) reaction following transplantation. Following encounter with alloantigen, activated B cells migrate to the T- and B-cell interface and receive T-cell help. Some of the helped B cells differentiate into memory B cells or plasma cells, while the rest enter into a germinal center to emerge as high-affinity and class-switched memory B cells and plasma cells. Memory B cells tend to have low levels of somatic hypermutations and lower B-cell receptor (BCR) affinity compared with plasma cells, and cells generated pre-GC tend to be of lower affinity than cells generated post-GC.