REPEAT HLA CLASS II MISMATCHES ARE ASSOCIATED WITH INCREASED GRAFT LOSS OF THE SECOND KIDNEY TRANSPLANT: a contemporary Collaborative Transplant Study (CTS) registry analysis.

REPEAT HLA CLASS II MISMATCHES ARE ASSOCIATED WITH INCREASED GRAFT LOSS OF THE SECOND KIDNEY TRANSPLANT: a contemporary Collaborative Transplant Study (CTS) registry analysis. L. Pipeleers1, C. Unterrainer2, M-P. Emonds3, K.M. Wissing1, H. Tran2 (1UZBrussel, Brussel, Belgium; 2Heidelberg University Hospital, Heidelberg, Germany; 3KULeuven, Leuven; Belgian Red Cross-Flanders, Mechelen, Belgium). Re-exposure to repeat HLA antigen mismatches (RMM) has been associated with inferior outcomes of the second kidney transplant, but uncertainty remains as to whether all RMM with the first donor should be systematically avoided. We hypothesized that in an era of widely available highly sensitive HLA antibody identification techniques, RMM with detectable antibodies are avoided and allowing other RMM would no longer be associated with adverse graft outcomes. To investigate this question, we performed an analysis of the CTS registry including data of 6711 patients who had received a second kidney transplantation between 2010 and 2021, with at least one HLA-A, -B or -DR mismatch. 1438 patients were transplanted with ≥ 1 repeat HLA antigen mismatch (RMM+) and 5273 without any RMM (RMM-). Multivariable analysis identified an increased risk of 1-year death-censored graft loss in the RMM+ group compared to the RMM-group (hazard ratio HR 1.27; 95% confidence interval 95%CI 1.01 to 1.60; P=0.04), but no statistically significant difference in 5-year death-censored graft loss (HR 1.12; 95% CI 0.93 to 1.33; P=0.23). In RMM+ recipients who were transplanted with a HLA-class II RMM only, there was a doubling of the risk of 1-year death-censored graft loss (HR 2.03; 95% CI 1.40 to 2.94; P < 0.001) and a 55% increase of the risk of 5-year death-censored graft loss (HR 1.55; 95% CI 1.15 to 2.10; P=0.004) compared to the RMM- group. For HLA class I RMM only, no significantly increased risk was observed for 1-year (HR 1.10; 95% CI 0.83 to 1.45; P=0.52) and 5-year (HR 0.98; 95% CI 0.79 – 1.22; P=0.88) death-censored graft survival compared to RMM-. The results of this study indicate that HLA class II RMM have a detrimental impact on early and late graft survival in patients who receive a second kidney transplant even in modern era of improved antibody testing. In our opinion, the findings reaffirm the importance of DR-matching in kidney transplantation.