Human Leukocyte Antigen Mismatch is Associated with Grade 3 Primary Graft Dysfunction at 72 Hours Following Bilateral Sequential Lung Transplantation: A Single-Center, Retrospective Cohort Study

Background: The role of donor-recipient human leukocyte antigen (HLA) mismatch as a risk factor for developing primary graft dysfunction (PGD) after lung transplantation is not well understood. We describe a novel association between increased donor-recipient HLA mismatch and grade 3 PGD after bilateral lung transplantation. Methods: We retrospectively evaluated donor and recipient demographic data, co-morbidities, intraoperative interventions and outcomes in 99 consecutive adult patients undergoing primary bilateral lung transplantation. The primary outcome of this study was grade 3 PGD at 72 hours. Secondary outcomes included intensive care and hospital lengths of stay and mortality. Results: Eighteen patients (18%) met criteria for grade 3 PGD at 72 hours postoperatively. More non-Caucasian recipients (27.8% vs. 7.4%, p=0.026), and more patients with interstitial lung disease (72.2% vs 43.2%, p=0.031) developed grade 3 PGD. The use of inhaled epoprostenol (OR 4.38, 95% CI: 1.02-20.16, p=0.048), increased HLA mismatches (OR 2.85, 95% CI: 1.31-7.45, p=0.017) and the use of each 250mL unit of PRBCs during the intraoperative period (OR 0.77, 95% CI: 0.58-0.97, p=0.048) were independently associated with grade 3 PGD. Patients diagnosed with grade 3 PGD spent significantly longer time in the intensive care unit (22 days [6;74 days] vs. 7 days [2;83 days], p=<0.001) and hospital (30.5 days [10;83 days] vs. 18 days [3;97 days], p=0.012), and survival was significantly worse for those with PGD3 at 72 hours (log-rank p=0.009). Conclusion: Our data indicate, for the first time, that HLA donor-recipient mismatch is an independent risk factor for developing grade 3 PGD at 72 hours after bilateral lung transplantation.