Acute antibody-mediated rejection of renal transplant: Pathogenetic and diagnostic considerations

Context. - Acute antibody-mediated rejection (AMR) has emerged recently as an important cause of graft failure. Objective. - To review the pathogenetic, clinicopathologic, and diagnostic considerations of AMR. Data Sources. - Review of literature and the authors' experience. Conclusions. - Acute antibody-mediated rejection is mediated by antibodies specific for donor antigens, which bind to target antigens and activate the complement system, culminating in tissue injury. The clinical manifestation of AMR is not specific, and transplant biopsy is needed for diagnosis. The glomeruli show thrombosis or neutrophils or mononuclear leukocytes in capillary lumens. The tubulointerstitial compartment shows edema, hemorrhage, necrosis, mild inflammation, and neutrophils or mononuclear leukocytes in the peritubular capillary lumens. The blood vessels show thrombosis, thrombotic microangiopathy, fibrinoid necrosis, or transmural vasculitis. Strong staining for C4d in the peritubular capillaries is characteristic. A definitive diagnosis of AMR requires (1) morphologic evidence of acute tissue injury, (2) immunopathologic evidence for antibody action, and (3) serologic evidence of circulating donor-specific antibodies. Acute antibody-mediated rejection should be suspected if some but not all 3 criteria are met. Since effective treatment is currently available, accurate and timely diagnosis of AMR is essential.