Kidney allograft survival after acute rejection, the value of follow-up biopsies

Kidney allografts are frequently lost due to alloimmunity. Still, the impact of early acute rejection (AR) on long-term graft survival is debated. We examined this relationship focusing on graft histology post-AR and assessing specific causes of graft loss. Included are 797 recipients without anti-donor antibodies (DSA) at transplant who had 1 year protocol biopsies. 15.2% of recipients had AR diagnosed by protocol or clinical biopsies. Compared to no-AR, all histologic types of AR led to abnormal histology in 1 and 2 years protocol biopsies, including more fibrosis + inflammation (6.3% vs. 21.9%), moderate/severe fibrosis (7.7% vs. 13.5%) and transplant glomerulopathy (1.4% vs. 8.3%, all p < 0.0001). AR were associated with reduced graft survival (HR = 3.07 (1.92-4.94), p < 0.0001). However, only those AR episodes followed by abnormal histology led to reduced graft survival. Early AR related to more late alloimmune-mediated graft losses, particularly transplant glomerulopathy (31% of losses). Related to this outcome, recipients with AR were more likely to have new DSA class II 1 year posttransplant (no-AR, 11.1%; AR, 21.2%, p = 0.039). In DSA negative recipients, early AR often leads to persistent graft inflammation and increases the risk of new DSA II production. Both of these post-AR events are associated with increased risk of graft loss. This study examines the relationship between early acute rejection and graft survival in unsensitized recipients of conventional kidney transplants and finds that early acute rejection leads to more fibrosis and inflammation at one and two years, formation of de novo class II donor-specific antibodies, and subsequently more late alloimmune graft loss related to chronic antibody-mediated rejection. See editorial by Nickerson and Rush on page 2239.