Glycocalyx damage marker syndecan-1 correlates with early allograft dysfunction during hypothermic liver machine perfusion
Laurin Rauter1, Judith Schiefer2, Pierre Raeven2, Öhlinger Thomas2, Marija Spasic1, Effimia Pompouridou1, Jule Dingfelder1, Andreas Salat1, Zoltan Mathé1, Georg Györi1, Thomas Soliman1, Dagmar Kollmann1, Gabriela Berlakovich1.
1Department of General Surgery, Division of Transplantation, Medical University of Vienna, Vienna, Austria; 2Department of Anesthesia, Intensive Care Medicine and Pain Medicine, Medical University of Vienna, Vienna, Austria
Introduction: The endothelial glycocalyx is mainly consisting of Syndecan-1 (Sdc-1) which is released into human serum upon glycocalyx degradation. Glycocalyx alterations are connected to different aspects of organ damage and have been recently investigated in the context of liver transplantation. Due to shortage of donor organs, new preservation methods as hypothermic oxygenated machine perfusion (HOPE) have been introduced to enable transplantation of organs with a higher risk profile. For safe expansion of the donor pool, reliable organ assessment markers for evaluation during machine perfusion are missing. We aimed to measure glycocalyx damage during hypothermic liver perfusion.
Methods: HOPE was performed with the Organ Assist® perfusion system on 40 livers, prior to organ transplantation. Samples were collected during (perfusate at 0 and 60 min) and after HOPE (effluent). Sdc-1 concentration in samples was measured by ELISA as indicator for glycocalyx destruction. We compared clinical parameters with Sdc-1 levels in patients regarding the development of early allograft dysfunction (EAD) using Mann-Whitney U test, Pearson correlation and receiver operating characteristics (ROC).
Results: The 13 patients which developed EAD, showed an elevation in Sdc-1 concentration compared to non-EAD patients during HOPE at 0 min: [598 (±526) vs. 276 (±150) ng/ml; p=0.076] and 60 min: [1099 (±739) vs. 521 (±382) ng/ml; p=0.016], as well as afterwards in the effluent: [2074 (±1273) vs. 443 (±226) ng/ml; p=0.001 (n=15, 4 with EAD)]. Concentration of Sdc-1 during HOPE correlated with EAD at 0 min: (R=0.433, p=0.006), at 60 min: (R=0.471, p=0.003) and in the effluent: (R=0.769, p<0.001, n=15, 4 with EAD). Furthermore, an association between EAD and Sdc-1 concentrations was indicated by ROCs: during HOPE at 60 minutes: (AUC=0.704 and p=0.018) and in the effluent: (AUC=1 and p=0.004 (n=15, 4 with EAD)). No association of graft survival with Sdc-1 (p=0.339) was detected in cox regression analysis however, reduced graft survival (log-rank=0.009) of EAD patients compared to those without EAD could be shown.
Conclusion: We found that measuring glycocalyx degradation during HOPE could indicate transplantation outcome regarding EAD. Consequently, we argue that Sdc-1 could be a useful biomarker for organ assessment during HOPE.
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