Establishment of Rat Model of Acute Antibody-Mediated Rejection in Kidney Transplantation.

Abstract

Acute antibody-mediated rejection (AAMR) remains a major obstacle to long-term graft survival in kidney transplantation. The pathophysiology of AAMR is primarily driven by donor-specific antibodies (DSA) that trigger complement activation, leading to endothelial cell injury, vasculitis, and graft dysfunction. Despite advancements in immunosuppressive therapies, the treatment of AAMR remains suboptimal. Therefore, the development of reliable animal models for AAMR is crucial for understanding its mechanisms and evaluating potential therapeutic interventions. In this study, a rat model of AAMR was established by sensitizing recipient Lewis rats with donor Brown Norway rat skin grafts for 14 days prior to kidney transplantation. No immunosuppressive agents were administered to the recipients throughout the study. Survival analysis demonstrated significantly reduced graft survival in the presensitized allogeneic group compared with the non-presensitized group (6.2 &#xb1; 1.1 d vs 10.0 &#xb1; 0.7 d, P < 0.001). The levels of serum DSA-IgG significantly increased from the 7th day after skin transplantation and continued to rise until the 5th day after kidney transplantation, and the levels of serum DSA-IgM significantly increased on the 7th and 14th days after skin transplantation. Starting 6 h after kidney transplantation, the allografts began to show signs of glomerulitis, peritubular capillaritis, and C4d deposition in capillaries. Starting from 3 days after kidney transplantation, significant allograft damage and tubular necrosis were observed. These changes gradually worsened over time and are all consistent with the characteristics of AAMR. This model effectively recapitulates the key features of AAMR, providing a robust platform for future studies on underlying mechanisms and potential treatments.