Higher M30 and high mobility group box 1 protein levels in ex vivo lung perfusate are associated with primary graft dysfunction after human lung transplantation

Background: Ex vivo lung perfusion (EVLP) enables assessment of marginal donor lungs for transplantation, with similar clinical outcomes to conventional lung transplantation. We investigated whether cell death–related proteins in the EVLP perfusate could predict primary graft dysfunction (PGD) after transplantation. Methods: M30 (indicating epithelial apoptosis), M65 (indicating total epithelial cell death), and high mobility group box 1 (HMGB-1, related to cell death and inflammation) protein levels in EVLP perfusate were measured by enzyme-linked immunosorbent assay and correlated with clinical outcomes. Results: From 100 sequential EVLP patients, 79 lungs were transplanted. Patients who were bridged with extracorporeal life support (ECLS, n = 6) or who received lobar/single lung (n = 25) were excluded. PGD grade 3 (partial pressure of arterial oxygen/fraction of inspired oxygen <200 or need for ECLS) developed in 11 at any time within 72 hours after transplantation (PGD Group). PGD grade 3 did not develop in 34 patients (Control Group). M30 was significantly higher in the PGD Group than in the Control Group at 1 hour (PGD: 73.3 ± 24.9, control: 53.9 ± 15.9 U/liter; p < 0.01) and at 4 hours (PGD: 137.0 ± 146.6, Control: 72.4 ± 40.0 U/liter; p = 0.046) of EVLP. The increase of HMGB-1 from 1 to 4 hours of EVLP was significantly greater in the PGD Group (PGD: 37.0 ± 25.4, Control: 7.2 ± 16.8 ng/ml; p < 0.001). Higher levels of or a greater increase in M30 and a greater increase in HMGB-1 were associated with higher mortality in Cox regression. Conclusions: Levels of M30 and HMGB-1 in the EVLP perfusate correlate with PGD after lung transplantation and might therefore be useful biomarkers to improve donor lung assessment during EVLP.