Polysulfide Nanoparticles Ameliorate Ischaemia Reperfusion Injury in Renal Transplantation and Improve Kidney Function Post-Transplantation

Stone, J. P.; D'Arcy, R.; Geraghty, A.; Amin, K.; Montero-Fernandez, A.; Dabare, D.; Ghibaudi, M.; Francini, N.; Coradello, G.; Bramhall, J.; Galwey, N. W.; Ruseva, M.; Tirelli, N.; Fildes, J.

doi:10.1101/2023.06.21.545864

bioRxiv · 10.1101/2023.06.21.545864

Polysulfide Nanoparticles Ameliorate Ischaemia Reperfusion Injury in Renal Transplantation and Improve Kidney Function Post-Transplantation

Stone, J. P.·D'Arcy, R.·Geraghty, A.·Amin, K.·Montero-Fernandez, A.·Dabare, D.·Ghibaudi, M.·Francini, N.·Coradello, G.·Bramhall, J.·Galwey, N. W.·Ruseva, M.·Tirelli, N.·Fildes, J.

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Abstract

Ischemia-reperfusion injury (IRI) is a significant complication in kidney transplantation, often affecting the viability and function of organs. Normothermic machine perfusion (NMP) is a technique used to improve the condition of organs prior to transplantation. In this study, we show that incorporating antioxidant poly(propylene sulfide) nanoparticles (PPS-NPs) during cold-storage and NMP significantly enhances its efficacy in reducing IRI upon porcine kidney transplantation. We found that by scavenging reactive oxygen species, PPS-NPs reduced oxidative stress and inflammation that occurs during ischemia-reperfusion with oxidized DNA reduced 5.3x and both TNF- and complement activation approximately halved. Our studies show that this approach led to significantly improved hemodynamics, better renal function, and tissue health compared to NMP alone. The results suggest that incorporating PPS-NPs into transplantation protocols may expand the pool of kidneys suitable for transplantation and enhance overall transplantation success rates. The broader impact of this work could extend to other organ transplants, suggesting a wider application for nanoantioxidant technologies in organ preservation.

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Stone, J. P., D'Arcy, R., Geraghty, A., Amin, K., Montero-Fernandez, A., Dabare, D., Ghibaudi, M., Francini, N., Coradello, G., Bramhall, J., Galwey, N. W., Ruseva, M., Tirelli, N., Fildes, J.. 2023-06-22. Polysulfide Nanoparticles Ameliorate Ischaemia Reperfusion Injury in Renal Transplantation and Improve Kidney Function Post-Transplantation. https://doi.org/10.1101/2023.06.21.545864

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