Landscape of subclinical rejection in a large international cohort of pediatric kidney transplant recipients

Kidney allograft rejection occurs in clinically stable patients, but its long-term significance in children is unknown. Previous studies demonstrated that subclinical (SC) inflammation is associated with an increased risk of rejection. However, the prevalence and significance of SC antibody-mediated rejection (AMR) and the impact of SC rejection phenotypes on graft survival remains to be assessed. We included children who underwent transplantation from 8 centers in France and the United States performing surveillance biopsies and compared the risk of acute rejection and graft loss stratified on surveillance biopsies’ findings. In total, 1406 surveillance biopsies were performed in 776 kidney transplantation recipients including 134 (10%) SC borderline, 46 (3%) SC T cell–mediated rejection, 42 (3%) SC AMR, 9 (1%) SC mixed rejections. SC rejection was associated with acute rejection (5-year rejection-free survival of 88%, 78%, 68%, and 63% in the no rejection, SC borderline, SC T cell–mediated rejection, and SC AMR groups, respectively). Treatment of SC borderline lesions was not associated with a decreased incidence of clinical rejection. SC AMR was associated with a lower 5-year graft survival (P = .02). SC rejection is associated with acute rejection in stable pediatric kidney recipients, while SC AMR only is associated with an increased risk of allograft failure. Further studies evaluating the impact of treating these SC findings are needed.