A novel, customized 3D-printed perfusion chamber for normothermic machine perfusion of the kidney

Hameed, Ahmer; Dervish, Suat; Rogers, Natasha M.; Pleass, Henry; Hawthorne, Wayne J.

doi:10.1111/tri.13361

Cited by 2 publications

(2 citation statements)

References 8 publications

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“…The kidney was placed in a customized, 3D-printed perfusion chamber, with the renal vein left open. 22 Urine output (UO) was replaced with Hartmann’s solution. NMP was undertaken at a temperature of 37°C, with flow rates adjusted to maintain at a mean arterial pressure (MAP) of 75–85 mm Hg.…”

Section: Methodsmentioning

confidence: 99%

Brief Normothermic Machine Perfusion Rejuvenates Discarded Human Kidneys

Hameed

Patrick

et al. 2019

Transplantation Direct

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Section: Methodsmentioning

confidence: 99%

Brief Normothermic Machine Perfusion Rejuvenates Discarded Human Kidneys

Hameed

Patrick

et al. 2019

Transplantation Direct

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“…The 1 hour time period was chosen as it has been shown to be effective in human kidney transplantation after initial CS, and is now the subject of a multi-center RCT in the UK 11,12 . The kidney was placed in a customized 3D-printed copolyester perfusion chamber during NMP 43 . Continuous infusions of verapamil (0.5 mg/hr), 5% dextrose (5 ml/ hr), and M199 nutrient solution containing 100 IU of actrapid and multivitamins (1 vial of Soluvit N dissolved in Vitalipid N; Fresenius Kabi, Bad Homburg, Germany) (100 ml at 20 ml/hr) were also provided.…”

Section: Immunohistochemistrymentioning

confidence: 99%

Pharmacologic targeting of renal ischemia-reperfusion injury using a normothermic machine perfusion platform

Hameed

Burns

et al. 2020

Sci Rep

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(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.

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A novel, customized 3D-printed perfusion chamber for normothermic machine perfusion of the kidney

Cited by 2 publications

References 8 publications

Brief Normothermic Machine Perfusion Rejuvenates Discarded Human Kidneys

Brief Normothermic Machine Perfusion Rejuvenates Discarded Human Kidneys

Pharmacologic targeting of renal ischemia-reperfusion injury using a normothermic machine perfusion platform

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