Kiyohiko Hotta

Chronic antibody‐mediated rejection of kidney transplantation is a major cause of late‐stage graft loss. Donor‐specific antibodies are the main cause of antibody‐mediated rejection; in particular, de novo donor‐specific antibodies are a risk factor for chronic active antibody‐mediated rejection. The level of de novo donor‐specific antibodies tends to increase with time throughout long‐term graft survival. Donor‐specific antibodies induce humoral rejection through complement activation, which results in tissue injury and coagulation. Additionally, complement activation promotes the migration of inflammatory cells through the innate immune response, causing endothelial injury. This inflammatory response may cause persistent glomerulitis and peritubular capillaritis, leading to fixed pathological lesions that impair graft function. No treatment has been established for chronic antibody‐mediated rejection, a condition in which antibody‐mediated rejection becomes irreversible. Thus, antibody‐mediated rejection must be detected and treated while it is still reversible. In this review, we discuss the development of de novo donor‐specific antibodies and the mechanisms leading to chronic antibody‐mediated rejection and summarize the current treatment options and the latest biomarkers for detecting chronic antibody‐mediated rejection at an earlier stage.