The relationship between pathologic lesions of active and chronic antibody-mediated rejection in renal allografts

The Banff classification of renal allograft pathology defines specific morphologic lesions that are used in the diagnosis of active (glomerulitis, peritubular capillaritis, endarteritis) and chronic (transplant glomerulopathy, peritubular capillary basement membrane multilayering, transplant arteriopathy) antibody-mediated rejection (ABMR). However, none of these individual lesions are specific for ABMR, and for this reason Banff requires 1 or more additional findings, including C4d deposition in peritubular capillaries, presence of circulating donor-specific antibodies (DSAs), and/or expression in the tissue of transcripts strongly associated with ABMR, for a definitive diagnosis of ABMR to be made. In addition, while animal studies examining serial biopsies have established the progression of morphologic lesions of active to chronic ABMR as well as intermediate forms (chronic active ABMR) exhibiting features of both, clear documentation that lesions of chronic ABMR require the earlier presence of corresponding active and intermediate lesions is less well established in human renal allografts. This review examines temporal relationships between key morphologic lesions of active and chronic ABMR in biopsies of human grafts, likely intermediate forms, and findings for and possibly against direct and potentially interruptible progression from active to chronic lesions.