Clinical importance of extended second field high‐resolution HLA genotyping for kidney transplantation

The need for extended second field high‐resolution (2F‐HR) HLA genotyping in kidney transplantation is debated. In a cohort of 1000 kidney transplants, we evaluated the impact of different HLA genotyping levels on the assignment of donor‐specific anti‐HLA antibodies (DSA) and investigated whether inference of 2F‐HR genotypes from low‐resolution (LR) genotypes could be used to correctly assign DSA. Based on LR genotypes, 224 pretransplant DSAs were present in 140 patients and absent in 860 patients (DSA(neg) group). With extended 2F‐HR HLA genotyping, we confirmed 173 DSA (77.2%) in 108 (77.1%) patients (2F‐HR(pos)LR(pos)DSA group) and excluded DSA in 32 patients (22.9%) (2F‐HR(neg)LR(pos)DSA group). Kaplan‐Meier curves showed that 10‐year graft survival rates were similar between the DSA(neg) and 2F‐HR(neg)LR(pos)DSA groups (82.4% vs 93.8%; P = .27) and confirmed that DSA determined using LR typing but not confirmed using 2F‐HR typing were indeed misclassified. By inferring 2F‐HR genotypes using HaploStats, DSA still could not be correctly assigned in 23.3% of cases. We conclude that extended 2F‐HR typing of the donor‐recipient pairs is relevant for the correct assessment of DSA. Although inference of 2F‐HR genotypes may improve the assessment of DSA in some cases, significant misclassification occurs, and warrants caution in using inferred HLA results for clinical and research purposes.