Pro-Inflammatory Milieu in Human Kidney Perfusates Treated with Hypothermic Pulsatile Machine Perfusion

Hypothermic Machine Perfusion (HMP) has been shown to decrease Delayed Graft Function (DGF) and improve outcomes of deceased donor kidney transplants. Although the mechanisms of protection afforded by HMP have not yet been defined, this study tested the hypothesis that HMP improves transplant outcomes by clearing pro-inflammatory molecules from the allograft during pumping. Here we report on 26 allografts preserved via pulsatile HMP at our organ procurement organization that were prospectively evaluated for the time-dependent clearance of cytokines, chemokines and injury markers during their time on pump. Of the cytokines and chemokines measured, IL-1RA, IL-6, IL-18, INFγ, and MCP-1 were increased in the pump perfusate over time and were correlated with markers of kidney injury. Over time on pump, the 'Danger' molecule HMGB1 appeared in the perfusate, and perfusate samples activated T-cells ex vivo. The data from this prospective study show that HMP is associated with a time-dependent clearance of pro-inflammatory cytokines, chemokines and danger molecules from donor allografts during the process of pumping, which may in part explain the beneficial effects of HMP.