Hypothermic Oxygenated New Machine Perfusion System in Liver and Kidney Transplantation of Extended Criteria Donors:First Italian Clinical Trial

Abstract

With the aim to explore innovative tools for organ preservation, especially in marginal organs, we hereby describe a clinical trial of ex-vivo hypothermic oxygenated perfusion (HOPE) in the field of liver (Lt) and kidney transplantation (Kt) from extended criteria Donors (ecD) after brain death. A matched-case analysis of donor and recipient variables was developed: 10 HOPE-ECD livers and kidneys (HOPE-L and HOPE-K) were matched 1:3 with livers and kidneys preserved with static cold storage (ScS-L and ScS-K). Hope and ScS groups resulted with similar basal characteristics, both for recipients and donors. Cumulative liver and kidney graft dysfunction were 10% (HOPE L-K) vs. 31.7%, in ScS group (p = 0.05). Primary non-function was 3.3% for SCS-L vs. 0% for HOPE-L. No primary nonfunction was reported in HOPE-K and SCS-K. Median peak aspartate aminotransferase within 7-days post-LT was significantly higher in SCS-L when compared to HOPE-L (637 vs.344 U/L, p = 0.007). Graft survival at 1-year post-transplant was 93.3% for SCS-L vs. 100% of HOPE-L and 90% for SCS-K vs. 100% of HOPE-K. Clinical outcomes support our hypothesis of machine perfusion being a safe and effective system to reduce ischemic preservation injuries in Kt and in Lt.

Organ Restoration With Normothermic Machine Perfusion and Immune Reaction

“…There were no changes in IL-2 production by CD8+ T cells after NMLP. Studies have identified that within the perfusate and liver tissue samples in both NMP and SCS there is a significant increase in regulatory T helper cells and regulatory cytokines implementing immune tolerance in liver grafts (65,67). We also see a statistically significant abundance of intrahepatic Tregs in NMP when compared to SCS (4.36% ± 3.27 vs. 1.9% ± 1.8, p = 0.0156), and in conjunction with the presence of IL-2 this promotes an expansion and proliferation of the Treg subset.…”

Circulating endothelial cells transiently increase in peripheral blood after kidney transplantation

“…Machine perfusion is increasingly used to preserve kidneys and it provides an excellent opportunity to examine the kidney before transplantation 20 , 21 . In the present study, we confirmed that grafts release EC after perfusion.…”

Assessing Kidney Graft Viability and Its Cells Metabolism during Machine Perfusion

“…As for the case of SCS, HMP slows down the cell metabolism, reducing oxygen requirements and ATP depletion. Additional research focuses on a vasoprotective effect of HMP, by potentially maintaining the hemodynamic stimulation of the endothelium, decreasing the vasospasm, facilitating the expression of protective flow dependent genes and maintaining the patency of the vascular bed [ 30 , 31 , 32 ]. In this respect, the use of pulsatile flow in HMP appears to be the important factor in HMP effects versus non-pulsatile flow, in order to ensure benefits of HMP compared to SCS [ 6 ].…”