Simply Adding Oxygen during Hypothermic Machine Perfusion to Combat the Negative Effects of Ischemia-Reperfusion Injury: Fundamentals and Current Evidence for Kidneys

Abstract

The use of high-risk renal grafts for transplantation requires optimization of pretransplant preservation and assessment strategies to improve clinical outcomes as well as to decrease organ discard rate. With oxygenation proposed as a resuscitative measure during hypothermic machine preservation, this review provides a critical overview of the fundamentals of active oxygenation during hypothermic machine perfusion, as well as the current preclinical and clinical evidence and suggests different strategies for clinical implementation.

PO2 21% oxygenated hypothermic machine perfusion in kidney transplantation: Any clinical benefit?

“…Considering the metabolic reactivity of oxygen, several factors should be considered when implementing oxygenation in HMP: graft quality and severity of accumulated ischemic injury, perfusate partial pressure of oxygen and duration of oxygenation. 4–6…”

“…[1][2][3] Oxygen does play a critical role in graft ischemia-reperfusion injury (IRI). [4][5][6] As a matter of fact, the pathogenesis of IRI comprise both oxygen deprivation during ischemia time, resulting in ATP and antioxidants depletion due to anaerobic metabolism, and production of reactive oxygen species (ROS) during reperfusion, with cytotoxic effect. [4][5][6] Two types of HMP are currently available, oxygenated HMP and non-oxygenated HMP.…”

“…[4][5][6] As a matter of fact, the pathogenesis of IRI comprise both oxygen deprivation during ischemia time, resulting in ATP and antioxidants depletion due to anaerobic metabolism, and production of reactive oxygen species (ROS) during reperfusion, with cytotoxic effect. [4][5][6] Two types of HMP are currently available, oxygenated HMP and non-oxygenated HMP. In animal model studies, graft oxygenation during HMP seems to exert a protective metabolic effect, but in clinical practice, data supporting a real benefit are limited and heterogeneous.…”

Donor Death Category Is an Effect Modifier Between Cold Ischemia Time and Post-transplant Graft Function in Deceased-Donor Kidney Transplant Recipients

“…Gregorini et al applied mesenchymal stromal cells (MSCs) and found that the addition of MSC/MSC-derived extracellular vesicles to Belzer solution during hypothermic machine perfusion protected the kidney from ischemic injury by preserving the enzymatic machinery essential for cell viability and protecting the kidney from reperfusion damage ( 35 ). To reduce the injury caused by hypoxia, oxygenated perfusion seems to be a reasonable alternative ( 36 ). However, current clinical trial results of oxygenated hypothermic machine perfusion are discouraging ( 36 , 37 ).…”

“…To reduce the injury caused by hypoxia, oxygenated perfusion seems to be a reasonable alternative ( 36 ). However, current clinical trial results of oxygenated hypothermic machine perfusion are discouraging ( 36 , 37 ). Normothermic machine perfusion (NMP) can mimic normal physiological perfusion of kidneys by oxygen carriers and can enable the reduction or avoidance of cold ischemia.…”