Impact of Excluding Anti-HLA-C and -DP Antibodies From the Allocation System on Kidney Transplant Access

Given the risk of antibody-mediated rejection, most kidney graft allocation systems define unacceptable antigens to prevent transplantation in the presence of donor-specific antibodies. Anti-HLA-C and anti-HLA-DP antibodies are often not included in these algorithms, including the French allocation system, despite growing evidence supporting their pathogenicity. In routine clinical practice, however, these antibodies are frequently considered by transplant teams when evaluating donor offers, creating a discrepancy between allocation scores and real-world access to transplantation. We aimed to evaluate the impact of this discrepancy on access to kidney transplantation. We conducted a retrospective study including 2160 patients registered on the kidney transplant waiting list at our centre between 2009 and 2018, in whom anti-HLA-C and anti-HLA-DP antibodies were systematically considered in clinical decision-making similarly to other HLA antibodies. Anti-HLA-C/DP antibodies were detected in 325 patients (15.1%). Incorporating these antibodies into cPRA calculations resulted in a near-systematic increase in cPRA values (mean increase, 5.5 ± 11.3). Using relative loss of graft access (RLGA), 83.5% of patients experienced reduced estimated access to transplantation, including 21.5% who lost more than 75% of their access. Patients harbouring anti-HLA-C/DP antibodies also exhibited significantly reduced access to kidney transplantation in both univariable and multivariable analyses (HR = 0.52; 95% CI, 0.42-0.66; p = 2 × 10^-8), associated with higher immunological donor offer refusal rates (mean 25.7% vs. 1.8%, p < 2 × 10^-16). In conclusion, excluding anti-HLA-C and anti-HLA-DP antibodies from allocation algorithms, despite their consideration in routine clinical decision-making, is associated with reduced access to kidney transplantation, and their integration could improve equity among transplant candidates.