Abstract
Kidney transplantation remains the gold standard treatment for patients suffering from end-stage kidney disease. To meet the constantly growing organ demands grafts donated after circulatory death (DCD) or retrieved from extended criteria donors (ECD) are increasingly utilized. Not surprisingly, usage of those organs is challenging due to their susceptibility to ischemia-reperfusion injury, high immunogenicity, and demanding immune regulation after implantation. Lately, a lot of effort has been put into improvement of kidney preservation strategies. After demonstrating a definite advantage over static cold storage in reduction of delayed graft function rates in randomized-controlled clinical trials, hypothermic machine perfusion has already found its place in clinical practice of kidney transplantation. Nevertheless, an active investigation of perfusion variables, such as temperature (normothermic or subnormothermic), oxygen supply and perfusate composition, is already bringing evidence that ex-vivo machine perfusion has a potential not only to maintain kidney viability, but also serve as a platform for organ conditioning, targeted treatment and even improve its quality. Many different therapies, including pharmacological agents, gene therapy, mesenchymal stromal cells, or nanoparticles (NPs), have been successfully delivered directly to the kidney during ex-vivo machine perfusion in experimental models, making a big step toward achievement of two main goals in transplant surgery: minimization of graft ischemia-reperfusion injury and reduction of immunogenicity (or even reaching tolerance). In this comprehensive review current state of evidence regarding ex-vivo kidney machine perfusion and its capacity in kidney graft treatment is presented. Moreover, challenges in application of these novel techniques in clinical practice are discussed.
Highlights
Kidney transplantation (Tx) remains the gold-standard treatment for end-stage kidney disease
To meet growing organ demands, utilization of grafts donated after circulatory death (DCD), or retrieved from extended criteria donors (ECD) is unavoidable
CORM401 was delivered to kidneys originating from a porcine DCD model in a pulsatile manner at 37◦C for 20 min followed by immediate reperfusion with autologous blood
Summary
Kidney transplantation (Tx) remains the gold-standard treatment for end-stage kidney disease. Several experimental models demonstrated the superiority of a short period of NMP after HMP [52] or prolonged SCS [58] vs HMP-only Contrary to those findings, in the recent study by Vallant et al porcine kidneys after 4 h of end-ischemic HMP had higher urine output, oxygen consumption, perfusate flow rates, and lower number of apoptotic cells than paired grafts that underwent 4 h of end-ischemic NMP [70]. One of the leading groups in kidney graft preservation at the University of Toronto explored prolonged NMP up to 16 h in porcine experiments They revealed that long-term normothermic preservation significantly reduces tubular injury and improves kidney function, compared to SCS, HMP or end-ischemia short-term NMP [72,73,74,75,76,77,78]. Intra-arterial delivery of MSC directly to the kidney graft is feasible, efficient, prolongs MSC survival and cell-to-cell contact in situ, as well as, off-target migration of infused cells is minimal [137, 138], supporting the idea that cell therapy could be successfully applied for organ preconditioning and repair ex-vivo prior to implantation
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