Abstract
Remarkable advances have been made in the pathophysiology, diagnosis, and treatment of antibody-mediated rejection (ABMR) over the past decades, leading to improved graft outcomes. However, long-term failure is still high and effective treatment for chronic ABMR, an important cause of graft failure, has not yet been identified. Chronic ABMR has a relatively different phenotype from active ABMR and is a slowly progressive disease in which graft injury is mainly caused by de novo donor specific antibodies (DSA). Since most trials of current immunosuppressive therapies for rejection have focused on active ABMR, treatment strategies based on those data might be less effective in chronic ABMR. A better understanding of chronic ABMR may serve as a bridge in establishing treatment strategies to improve graft outcomes. In this in-depth review, we focus on the pathophysiology and characteristics of chronic ABMR along with the newly revised Banff criteria in 2017. In addition, in terms of chronic ABMR, we identify the reasons for the resistance of current immunosuppressive therapies and look at ongoing research that could play a role in setting better treatment strategies in the future. Finally, we review non-invasive biomarkers as tools to monitor for rejection.
Highlights
Successful kidney transplantation (KT) provides a better quality of life and survival compared to transplant candidates (Gill et al, 2005; Oniscu et al, 2005; Finkelstein et al, 2012)
Lack of C4d staining is relatively common in chronic active antibody-mediated rejection (ABMR) (Gloor et al, 2007; Becker et al, 2016). These findings suggest that chronic active ABMR can occur in the absence of complement activation
Chronic ABMR: donor specific antibodies (DSA) >mean-fluorescence intensity (MFI) 1100; 20% reduction in eGFR; no severe fibrosis Late ABMR -BANFF 2013 (9 ptx: chronic active ABMR)
Summary
Reviewed by: Georg Böhmig, Medical University of Vienna, Austria Francesc J. Since most trials of current immunosuppressive therapies for rejection have focused on active ABMR, treatment strategies based on those data might be less effective in chronic ABMR. A better understanding of chronic ABMR may serve as a bridge in establishing treatment strategies to improve graft outcomes. In this in-depth review, we focus on the pathophysiology and characteristics of chronic ABMR along with the newly revised Banff criteria in 2017. In terms of chronic ABMR, we identify the reasons for the resistance of current immunosuppressive therapies and look at ongoing research that could play a role in setting better treatment strategies in the future.
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