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

Introduction Ischaemia-reperfusion injury (IRI) results in the pathophysiological generation of reactive oxygen species (ROS) with concurrent activation of the complement cascade. This manifests as delayed graft function, which has a significant impact on the longevity of the graft. We aimed to evaluate if ROS scavenging nanoparticles can be used to mitigate IRI related injury during normothermic machine perfusion (NMP).

Methods A randomised, two-stage, preclinical trial was used to assess the impact of poly(propylene sulfide) (polysulfide) nanoparticles (PPS-NPs) on parameters associated with IRI in a renal NMP system (experiment 1, n=6 vs 6). Paired porcine kidneys were randomised to receive either an NP-preservation flush followed by 6 hours of NMP with NP-perfusate, or control preservation flush and standard NMP. Following this, an allogeneic transplant-reperfusion model was used to evaluate if treatment with PPS-NPs improved renal haemodynamics post-transplantation (experiment 2, n=6 vs 6). Kidneys were perfused for 3 hours with or without NP, before being reperfused on a circuit primed with matched blood from genetically different donor pigs for 6 hours, without immunosuppression.

Results In experiment 1, all kidneys perfused well for 6 hours with physiological renal haemodynamics and biochemistry. Kidneys perfused with PPS-NPs had improved regional tissue perfusion on infra-red imaging. In experiment 2, renal haemodynamics were significantly improved during allogeneic reperfusion (post-transplant) after treatment with NP. Complement activation remained significantly lower in treated kidneys with a diminished TNF-α response. This translated into an improvement in tissue integrity.

Conclusion IRI was ameliorated following treatment with NPs during preservation and NMP. This was evidenced by an improvement in renal haemodynamics and diminished inflammatory markers upon reperfusion with allogeneic blood.