Evaluation of a Novel Method and Drug Repositioning to Protect ex vivo Kidney for Transplantation
New Technology, Therapies, eHealth & mHealth
Kidney transplantation is currently the best treatment option available for patients with kidney failure. Unfortunately, the need for kidneys is greater than the number of acceptable donors available. To increase access to transplantation, organs from higher risk donors are being used more frequently, though this results in greater risk of poor outcomes for patient post-transplant. Currently, donor organs are stored on ice until the time of transplant, during which the kidney suffers injury from the cold injury and lack of oxygen. Research from our group suggests that providing oxygen to kidneys at around room temperature in a mechanical pump can reduce injury, protect kidneys from inflammation, and improve their function. We are currently assessing clinically available re-purposed drugs to be used with our new device to further protect organs with the aim to improve kidney function/survival and utilize kidneys that we would never have considered for use in the past.
Objectives: Currently, donor organs are stored on ice until the time of transplant, during which the kidney suffers injury from the cold temperatures and lack of oxygen. Research from our group suggests that providing oxygen to kidneys at around room temperature utilizing a mechanical pump can reduce injury, protect kidneys from inflammation, and improve their function. Our objective is to investigate strategies for reducing pre-transplant injury and maintaining optimal organ function post-transplant, namely by assessing the impact of preservation temperature and the addition of repositioned drugs during reperfusion.
Innovation: We have successfully developed a donor kidney porcine model by clamping the renal pedicles in situ to mimic clinical warm ischemia or donation after circulatory death (DCD) conditions. As well, we have extensively studied the superiority of the subnormothermic oxygenated pump compared with hypothermic perfusion in our porcine model prior to human study; we have optimized numerous factors including perfusate composition, temperature, pressures, type of pump, nutritional supplementation and oxygenation. The innovation has enabled us to submit for a patent for this method. In addition, we have successfully re-modelled a renal perfusion-reperfusion pump-cassette system by adapting an existing hypothermic pump and incorporating into it an oxygenator suitable for adding drugs and gasotransmitters.
Beyond the innovation fund: The AMOSO project has generated exciting new knowledge and enough preliminary data from which we have secured multiple grants, including CIHR. Our work has received citations world-wide and is recognized by renowned journals. As such, the AMOSO innovation fund has potentiated significant advancement in transplantation research.
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2. Bhattacharjee, R. N. et al. Renal protection against ischemia reperfusion injury: Hemoglobin-based oxygen carrier-201 versus blood as an oxygen carrier in ex vivo subnormothermic machine perfusion. Transplantation 104, 482 -489 (2020).
3. Luke, P. P. W. et al. Comparison of Centrifugal and Pulsatile Perfusion to Preserve Donor Kidneys Using Ex Vivo Subnormothermic Perfusion. J. Investig. Surg. (2021) doi:10.1080/08941939.2020.1829212.
4. Bhattacharjee, R. et al. The impact of nutritional supplementation on donor kidneys during oxygenated ex vivo subnormothermic preservation. Transplant Direct 2022 8(10) e 1382.
5. Bhattacharjee RN, Richard-Mohamed M, Sun Q, et al. CORM-401 reduces ischemia reperfusion injury in an ex vivo renal porcine model of the donation after cardiac death. Transplantation 2018;102:1066-74.