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Prevention and treatment of antibody-mediated rejection of the renal allograft

Arjang Djamali, MD, MS, FASN
Daniel C Brennan, MD, FACP
Section Editor
Barbara Murphy, MB, BAO, BCh, FRCPI
Deputy Editor
Albert Q Lam, MD


Antibody-mediated rejection (ABMR) is the most common cause of allograft failure after kidney transplantation [1-4].

The cellular and molecular pathways that regulate ABMR are still under investigation. However, evidence suggests that B cell and plasma cell activation results in the generation of donor-specific antibodies (DSAs), which bind to human leukocyte antigen (HLA) or non-HLA molecules expressed on endothelial cells within the renal allograft [5,6]. In acute ABMR, antibodies bind to graft endothelium and activate complement-dependent and -independent mechanisms that recruit natural killer (NK) cells, polymorphonuclear neutrophils, platelets, and macrophages, which contribute to peritubular capillaritis, glomerulitis, cellular necrosis, thrombotic microangiopathy, and a relatively rapid decline in allograft function [5-7].

Chronic ABMR, on the other hand, is a distinct pathophysiological process resulting from a repetitive pattern of thrombotic events and inflammatory changes that lead to endothelial cell injury and allograft matrix remodeling [8,9]. It manifests histologically as transplant glomerulopathy and results in a slow and progressive decline in renal function [10].

Increasing evidence suggests that the prevention and treatment of antibody-mediated injury requires a combination of strategies to inhibit B cell development, maturation, and activity. Despite a relatively large number of observational studies, it is not clear which combination therapy is the safest and most effective.

The prevention and treatment of acute and chronic ABMR of the renal allograft will be reviewed here. The clinical features and diagnosis of ABMR and the treatment of acute T cell-mediated (cellular) rejection (TCMR) are discussed separately. (See "Clinical features and diagnosis of acute renal allograft rejection" and "Treatment of acute T cell-mediated (cellular) rejection of the renal allograft".)

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Literature review current through: Sep 2017. | This topic last updated: Oct 02, 2017.
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