Supplemental Digital Content is available in the text.

(NMP) is especially promising, and is now the subject of a multi-center randomized control trial (RCT) comparing it to CS alone in DCD kidneys 10-13. Most pharmacotherapeutics shown to ameliorate renal IRI have been unable to bridge the 'valley of death' (translational gap) to the clinic. This is at least partly attributable to the inherent difficulties and ethical considerations associated with the systemic use of such therapies in donors or recipients 14,15. NMP can serve as a bridge across this valley by providing a platform for direct, non-systemic drug treatment of the kidney whilst it is undergoing normal metabolic processes 15,16. Amongst the multiple anti-IRI agents tested in pre-clinical models, CD47-blocking antibody (αCD47Ab), recombinant thrombomodulin (rTM), and soluble complement receptor 1 (sCR1) are especially translatable as they have been safely employed for other clinical applications 17-25. However, the comparative efficacy of these agents has not been established. αCD47Ab ameliorates thrombospondin (TSP)-1 mediated IRI signaling, including inhibition of nitric oxide and promotion of oxidative stress 21. sCR1 is an inhibitor of the classical and alternative complement pathways, activation of which is important in IRI 26. rTM is an anti-coagulant molecule involved in the generation of activated protein C, although its efficacy in IRI may be more attributable to anti-inflammatory effects 17,27. Because IRI is characterized by the activation of multiple intersecting pathways 28,29 , it is also plausible that synergistic anti-IRI effects may be derived by delivering two or more of these agents together. The aims of this study were to directly compare the acute effects of αCD47Ab, sCR1, and rTM in a murine model of renal IRI and to establish the combined efficacy of two of the best agents. We then show that the chosen drug could be directly delivered to porcine DCD kidneys using NMP to enhance renal perfusion parameters and ameliorate IRI. The primary focus of this study is the immediate phase of IRI, which correlates to the immediate post-transplant setting and the risk of delayed graft function in higher risk renal allografts. Methods Animal work-ethics. All protocols were approved by the Western Sydney Local Health District Animal Ethics Committee, in accordance with the Australian code for the care and use of animals for scientific purposes (8 th Ed., 2013), developed by the National Health and Medical Research Council. Animal experiments adhere to the ARRIVE guidelines.

A viable and reproducible NMP system was established and tested in porcine kidneys, which was able to simulate graft function extra-corporeally. Further work is required to identify the most optimal perfusion conditions. Prior to its utilization in clinical transplantation, the system should be tested in non-transplanted human kidneys.

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A 50-year-old female underwent surgery for removal of a massive retroperitoneal sarcoma (RPS) involving the right hepatic lobe and the inferior vena cava (IVC), abdominal aorta, right lung, right hemi-diaphragm and pericardium. Resection of the RPS necessitated cross-clamping of the abdominal aorta, IVC and the hepatic artery. Cross-clamp time cannot be predicted prior to tumour resection and vascular re-construction. To prevent complications of prolonged cross-clamp time and distal hypo-perfusion, circulatory support was sought to facilitate the procedure. A perfusion circuit was designed to accommodate an easy and immediate redirection of blood flow from venovenous bypass (VVB) to veno-arterial bypass (VAB) without requiring a change of circuit and with minimum heparin administration. Furthermore, this circuit provides the added safety of an oxygenator and a heat-exchanger. Utilising the circuit enabled successful resection of the RPS. The patient was discharged from the intensive care unit (ICU) seven days later without any post-operative complications. This case report of a design of a perfusion circuit for the resection of RPS made use of a perfusion approach that had not previously been described and allowed for a reduction in the duration of ischaemic time and retroperitoneal bleeding.