Antibody-Mediated Rejection of Human Renal Allografts: An Electron Microscopic Study of Peritubular Capillaries

Abstract

The role of humoral rejection in acute and chronic rejection of human renal allografts other than in hyperacute rejection has not been well established, and its importance may be underestimated. Recently, a specific histological pattern of antibody-mediated rejection of renal allografts has been recognized. The antigens targeted by this mode of rejection are not well defined but are likely located on the endothelium of small vessels (arterioles and glomerular and peritubular capillaries). In both cellular and humoral rejection, the microvasculature of transplanted organs appears to be a main target of injury. This study describes the ultrastructural changes of peritubular capillaries, over a period of up to 8 months, in 14 biopsy specimens obtained from 5 renal allograft recipients diagnosed with “pure” antibody-mediated rejection. In peritubular capillaries, there is progression of injury from necrosis of endothelial cells with lifting and denudation of basement membrane to complete disappearance of capillaries. Acutely, acute tubular necrosis is a constant finding. At 2 to 3 months posttransplantation, the remaining capillaries are dilated, misshapen, and distorted, and are surrounded by a reduplicated and thickened basement membrane. These changes are associated with increased interstitial fibrosis and tubular atrophy, comparable to a sort of renal “asphyxial” death. The author concludes that in “pure” antibody-mediated rejection, the endothelium of peritubular capillaries is a main target of injury. The potential role of antibody-mediated rejection in acute and chronic rejection of renal allografts needs to be explored further.