416.3: Are HLA-A,B,DR and DQ-Mismatching Important for the Kidney Allocation Schemes?-UK Registry Data- an Artificial Intelligence Approach

Abstract

Introduction: Currently, there is inconsistency among different kidney allocation systems for deceased donors and paired exchange schemes in terms of assessment for HLA-A,B,DR and DQ mismatch. The aim of our study is to assess the effect of HLA-A,B,DR and DQ mismatch on kidney transplant graft survival in the current era. Methodology: All renal transplant patients registered in the United Kingdom Transplant Registry database between January 2005 till January 2015 were retrospectively reviewed. Patients with complete data about HLA-A,D,DR and DQ mismatch were included. Follow up was till April 2021.Patient with complete dataset were included in the study. Recipients with multiple organ transplant, previous renal transplants, or those with missing data about HLA mismatch were excluded from the study. For survival analysis, we fit a penalised Cox model to the entire set of data. We obtained the estimated set of alphas using estimated cross-validated grid-search. The variables included in the penalised cox model donor, recipient and transplant factors in addition to the HLA mismatches. Then we determined the set of alpha for evaluation using optimized cross-validated grid-search. Moreover, we visualised how the coefficients changed for varying α using ridge regression model. The regression models were adjusted for recipient factors (age, sex, ethnicity, diabetes, body mass index), transplant factors (HLA mismatches, calculated reaction frequency, cold ischemia time, delayed graft function, induction, and maintenance immunotherapy) and donor factors (donor type, donor creatinine at time of retrieval, donor age). Results: Median follow-up was 7.5 years. Among living donor kidney transplant recipients (n=4782), Incremental increase in HLA-DR mismatch touched statistical significance and was associated with worse survival (Two HLA-DR: HR=1.31, P=0.05, 95%CI: 1.0-1.72; One HLA-DR mismatch: HR=1.21, P=0.05, 95%CI: 1.00-1.47). None of the other categories of HLA mismatches were associated with worse graft outcomes (P>0.05 for each category).Other factors that played an important role in determining graft survival were delayed graft function (P<0.01), black ethnicity (HR=1.88, 95%CI:1.45-2.51, p<0.01), and donor age (HR=1.02, P<0.01). Among deceased donor kidney transplant recipients (n=7996), None of the HLA mismatches were associated with worse graft survival (P>0.05 for each category of HLA mismatches). The factors that played an important role in determining graft survival were delayed graft function (HR=1.84, 95%CI: 1.67-2.03, P<0.01), black ethnicity (HR=1.42, 95%CI:1.21-1.65, p<0.01), donor age (HR=1.02, P<0.01), and recipient age (HR=0.99, P<0.01). Conclusion: In the current era, HLA-DR mismatches are associated with worse graft outcomes among living donor transplants. However, none of the HLA mismatches are associated with worse graft outcomes among deceased donor kidney transplant recipients. Other factors that play an important role in determining graft survival are delayed graft function, donor age and black ethnicity.