Pathology of Chronic Humoral Rejection

Since its initial description in 2001, chronic humoral rejection (CHR, aka ‘chronic anti-body-mediated rejection’) has been recognized as a distinct and common cause of late graft dysfunction and loss. The pathology is focused on the microvascular components of the kid-ney, manifested by endothelial ‘activation’, multilamination of glomerular and peritubular capillary basement membranes, interstitial fibrosis and tubular atrophy, and sometimes chronic transplant arteriopathy. Diagnosis requires a biopsy and demonstration of the complement degradation product, C4d in peritubular and/or glomerular capillaries. For definitive diagnosis, detection of donor-specific anti-endothelial antibodies is required (most commonly to class II MHC antigens). Here we review the diagnostic criteria, pathologic manifestations, new molecular markers and related studies in experimental animals.