Retrospective cohort study of epitope-based virtual crossmatch allocation in a public transplant system (Pernambuco,...

Highly sensitized kidney transplant candidates face major barriers to transplantation because broad anti-HLA antibody reactivity substantially limits donor compatibility. We conducted a retrospective cohort study comparing two allocation eras in Pernambuco, Brazil: a pre-EpViX era (2005-2014; n=3,136) and an EpViX era (2016-2025; n=4,544). We evaluated the association between an epitope-informed definition of unacceptable antigens integrated with virtual crossmatching and access to deceased-donor kidney transplantation. The proportion of candidates who underwent transplantation was higher during the EpViX era (50%) than during the pre-EpViX era (36%) (p<0.001), while median waiting time among transplanted recipients decreased from 22 to 7 months (p<0.001). Among highly sensitized candidates (cPRA ≥80%), the estimated probability of transplantation at 12 months was 17% in the EpViX era compared with 3% in the pre-EpViX era. In adjusted analyses, listing during the EpViX era was associated with a higher likelihood of transplantation (HR 2.55; 95% CI 2.37-2.74; p<0.001). Epitope-level virtual crossmatch demonstrated high concordance with prospective complement-dependent cytotoxicity crossmatch, with sensitivity of 98.7%, specificity of 93.4%, and a negative predictive value of 99.6%. An allocation strategy incorporating an epitope-informed definition of unacceptable antigens was associated with greater access to deceased-donor kidney transplantation, including among highly sensitized candidates, while maintaining high concordance with prospective crossmatch testing.