The negative impact of T cell-mediated rejection on renal allograft survival in the modern era
Across 775 kidney transplant recipients on tacrolimus and mycophenolate with serial biopsies, about 30% had a first episode of borderline or greater T-cell-mediated rejection, and 64% of those had further episodes; both first and second episodes independently predicted graft loss.
Background
The prevalence and long-term consequences of T-cell-mediated rejection (TCMR) have been poorly characterised in the current era of tacrolimus and mycophenolate-based maintenance therapy, where early rejection rates are widely assumed to be low.
Key findings
Among 775 kidney transplant recipients with serial histology, roughly 30% had a first Banff borderline or greater TCMR, detected on for-cause biopsies in 17% and on surveillance biopsies in 13%. Follow-up biopsies showed persistent TCMR in 37.4% and subsequent TCMR in 26.3%, meaning 64% of affected recipients had further episodes. Alloimmune risk categories based on HLA-DR/DQ single-molecule eplet molecular mismatch correlated with the number of TCMR events (P = .002) and with Banff grade (P = .007). Both a first and a second TCMR event correlated with death-censored and all-cause graft loss after adjustment for baseline covariates and time-dependent covariates including delayed graft function and antibody-mediated rejection.
Clinical implications
A substantial proportion of recipients, especially those with intermediate or high HLA-DR/DQ molecular mismatch scores, appear under-immunosuppressed. The findings support molecular mismatch-informed risk stratification, surveillance histology in higher-risk recipients, and continued development of agents that prevent or treat TCMR more effectively.
Category
Transplant
Source
American Journal of Transplantation
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