Purpose: The concept of early rejection has evolved over time. In 2019, the Transplantation Society expert consensus focused on early rejection within 30 days post-transplantation, with aggressive allograft function deterioration induced by preexisting antibody. Despite this, few studies have systematically compared the clinical characteristics and long-term allograft prognosis between early and late rejection.
Methods: We retrospectively included 114 recipients who underwent allograft biopsy at the First Affiliated Hospital of Sun Yat-sen University from 2014 to 2022 and were diagnosed with ABMR based on the Banff 2019 criteria. The cohort was stratified into early rejection (n = 16, 14%) and late rejection (n = 98, 86%). Pre-existing antibodies were defined as preoperative positive panel reactive antibodies (PRA) or donor-specific antibodies. Allograft prognosis was compared between different types of ABMR.
Results: Late rejection was characterized by more severe chronic lesions (cg:0.68±1.07 vs 0.06±0.25, p = 0.023; ci: 1.32±0.62 vs 0.56±0.73, p<0.001; ct: 1.31±0.67 vs 0.69±0.70, p = 0.001) than early rejection. Allograft survival rates were markedly diminished in late rejection compared to early rejection (Two-year: 81.8% [74.0% - 94.0%] vs 100%, p = 0.017). Recipients with late rejection exhibited significantly poorer allograft outcomes in terms of two-year estimated glomerular filtration rate (40.63 [2.98 - 55.86] vs 68.6 [44.17 - 79.69], p = 0.001), two-year change in eGFR from rejection (-3.52 [-21.36 - 4.84] vs 20.88 [-1.24 - 42.26], p < 0.001), one-year cystatin C levels (2.21 [1.8 - 3.51] vs 1.27 [1.15 - 1.76], p = 0.048), and incidence of one-year proteinuria (48.08% vs 9.09%, p = 0.02) compared to recipients with early rejection. Similar adverse outcomes were noted in early and late rejection with preexisting antibodies. After adjusted by preexisting antibody, later rejection was independent for poorer two-year eGFR (coefficient -36.9, 95%CI -58.6 - -15.1, p = 0.001), two-year change in eGFR from rejection (coefficient -31.3, 95%CI -51.8 - -10.8, p = 0.003), one-year cystatin C levels (coefficient 1.76, 95%CI 0.01 - 3.51, p = 0.049).
Conclusions: Preexisting antibodies predominantly contribute to early rejection, while late rejection is associated with significantly worse allograft prognosis than early rejection. Regular testing of PRA is valuable for early detection of antibody-mediated rejection.