Endothelial glycocalyx damage marker syndecan-1 during hypothermic oxygenated machine perfusion of donor grafts facilitates prediction of early allograft dysfunction after liver transplantation

Background: Ischemia reperfusion injury (IRI) is a major contributing factor to organ damage in liver transplantation (LT) impacting donor organ quality and patient survival. IRI-inflicted graft injury can be reduced by using hypothermic oxygenated machine perfusion (HOPE) as a preservation strategy instead of static cold storage (SCS). The endothelial glycocalyx is highly sensitive to IRI and its degradation during graft preservation and reperfusion was previously associated with inferior postoperative outcome after LT. Here, we aimed to measure glycocalyx degradation during and after HOPE in order to evaluate its potential for viability-assessment during machine perfusion and outcome prediction in patients undergoing LT. Methods: Glycocalyx degradation was quantified via enzyme-linked immunoassay (ELISA) for its main component syndecan-1 (Sdc-1) in serum of 40 patients undergoing LT after HOPE. In addition, Sdc-1 was evaluated at multiple time points during HOPE. Patients were followed up for 3.5 years to assess postoperative complications including morbidity, the development of early allograft dysfunction (EAD) and graft survival. Results: Liver grafts which later developed EAD showed significantly higher Sdc-1 concentrations after 60 min of HOPE compared to grafts exhibiting normal postoperative function (P=0.02). Receiver operating characteristic analysis revealed a strong predictive potential with an area under the curve of 0.73. A cut-off at 808 ng/mL Sdc-1 at 60 min of HOPE allowed identification of a high-risk group with an incidence of EAD of 66.7%. Sdc-1 concentrations increased during all types of HOPE but were significantly higher in HOPE versus dual HOPE (D-HOPE) after 120 min of perfusion (P=0.02). Conclusions: Sdc-1 evaluated at 60 min during HOPE allows prediction of EAD after LT. Accordingly, Sdc-1 should be considered a potential additional biomarker for viability assessment during HOPE.