AUTHOR=Paessler Alicia , Kostakis Ioannis D. , Loukopoulos Ioannis , Arslan Zainab , Kessaris Nicos , Stojanovic Jelena TITLE=Living Donation and Pre-Emptive Transplantation Are More Important Than HLA Matching in Pediatric Kidney Transplantation: Results From a 33-Year Comparative OPTN Study JOURNAL=Transplant International VOLUME=Volume 38 - 2025 YEAR=2025 URL=https://www.frontierspartnerships.org/journals/transplant-international/articles/10.3389/ti.2025.15064 DOI=10.3389/ti.2025.15064 ISSN=1432-2277 ABSTRACT=Poorly HLA matched transplants have poorer long-term outcomes, however it is unclear whether living donation or pre-emptive transplantation can counteract the effects of HLA mismatches. We reviewed the long-term outcomes of paediatric kidney transplants with different HLA matches and aimed to identify other factors which may contribute significantly to long-term outcomes. We conducted a retrospective registry analysis of all pediatric kidney transplants from 1987–2020 in the USA from the OPTN Registry. These were analysed by HLA mismatches and compared by pre-transplant dialysis status and donor type. 21,500 patients were included for analysis. Overall, patients with unfavourable HLA matches had higher rates of delayed allograft function and lower allograft survival. However, patients with unfavourable HLA matched transplants from living donors had better allograft survival than patients with favourable HLA matched transplants from deceased donors (79% at 5 years vs. 71%, p < 0⋅01). Patients with pre-emptive unfavourable HLA matched transplants had better allograft and patient survival than patients with non-pre-emptive favourable HLA matched transplants (83% at 5 years vs. 78%, p = 0⋅02% and 98% vs. 96%, p < 0⋅01 respectively). In conclusion, living donation and pre-emptive transplantation have a more significant impact on clinical outcomes and lead to better allograft and patient survival than HLA matching.