Machine Perfusion of Extended Criteria Donor Organs: Immunological Aspects

Abstract

Due to higher vulnerability and immunogenicity of extended criteria donor (ECD) organs used for organ transplantation (Tx), the discovery of new treatment strategies, involving tissue allorecognition pathways, is important. The implementation of machine perfusion (MP) led to improved estimation of the organ quality and introduced the possibility to achieve graft reconditioning prior to Tx. A significant number of experimental and clinical trials demonstrated increasing support for MP as a promising method of ECD organ preservation compared to classical static cold storage. MP reduced ischemia-reperfusion injury resulting in the protection from inadequate activation of innate immunity. However, there are no general agreements on MP protocols, and clinical application is limited. The objective of this comprehensive review is to summarize literature on immunological effects of MP of ECD organs based on experimental studies and clinical trials.

The Role of Endothelins, IL-18, and NGAL in Kidney Hypothermic Machine Perfusion

“…MP offers the advantage of preventing mitochondrial and tissue damage. In static cold storage (SCS), the massive accumulation of metabolites derived from anaerobic respiration during the ischemic phase increases the hazard caused by oxidative stress in reperfusion [ 12 , 13 ]. There are also promising experimental strategies of upgrading MP with oxygenation (hypothermic oxygenated perfusion: HOPE) or with an O 2 carrier with anti-oxidant capacities (normothermic machine perfusion: NMP), resulting in improved kidney recovery and an enhanced late graft outcome [ 14 ].…”

The Role of Metabolomics in Current Concepts of Organ Preservation

“…Liver, kidney, heart, lung and, to some extent, pancreas and intestine Tx are incorporated into routine clinical care worldwide, and both patient and allograft survival are continuing to improve [ 1 ]. However, the growing disparity between organ supply and demand has led to the increasing use of donation after circulatory death (DCD) and extended criteria donor (ECD; aged ≥60 years or aged 50–59 years with vascular comorbidities) allografts [ 2 , 3 , 4 ], despite their higher susceptibility to ischemia-reperfusion injury (IRI) and consecutive inferior outcomes, including mortality and morbidity after Tx [ 5 , 6 ].…”

“…The allograft, metabolically impaired during warm and cold ischemia (WI and CI), is further damaged by a paradox reperfusion injury after revascularization and re-oxygenation. Short-term and long-term complications including post-reperfusion syndrome, delayed graft function (DGF) and even immune activation have been associated with IRI [ 5 , 8 ].…”

“…The accurate evaluation of allograft quality is essential in order to prevent unjustified donor organ rejection [ 13 , 14 ], and to estimate Tx outcomes. Additionally, MP offers a unique platform to facilitate intervention and modification to further optimize ECD grafts [ 5 , 15 ]. However, it remains unclear which temperature setting is preferable for optimal organ preservation [ 16 ].…”

“…However, it remains unclear which temperature setting is preferable for optimal organ preservation [ 16 ]. Hypothermia slows metabolism and oxygen consumption, so that organs can survive longer without nutrient supplements, while normothermia preserves the graft at a near-physiological condition [ 5 ].…”