Treatment of transplant kidneys during machine perfusion.

The increasing use of donation after circulatory death (DCD) and extended criteria donor (ECD) organs has raised awareness of the need to improve the quality of kidneys for transplantation. Treating kidneys during the preservation interval could improve early and long-term graft function and survival. Dynamic modes of preservation including hypothermic machine perfusion (HMP) and normothermic machine perfusion (NMP) may provide the functional platforms to treat these kidneys. Therapies in the field of regenerative medicine including cellular therapies and genetic modification and the application of biological agents targeting ischaemia reperfusion injury (IRI) and acute rejection are a growing area of research. This review reports on the application of cellular and gene manipulating therapies, nanoparticles, anti-inflammatory agents, anti-thrombolytic agents and monoclonal antibodies administered during HMP and NMP in experimental models. The review also reports on the clinical effectiveness of several biological agents administered during HMP. All of the experimental studies provide proof of principle that therapies can be successfully delivered during HMP and NMP. However, few have examined the effects after transplantation. Evidence for clinical application during HMP is sparse and only one study has demonstrated a beneficial effect on graft function. More investigation is needed to develop perfusion strategies and investigate the different experimental approaches.