188 Targeting human cytomegalovirus in donor kidneys by the ex vivo delivery of a novel fusion toxin protein during normothermic machine perfusion

Abstract Introduction Cytomegalovirus (CMV) causes minimal harm in its latent state. However, transplanting a kidney from a CMV seropositive donor puts an immunocompromised seronegative recipient at risk of severe CMV infection and graft failure. Fusion toxin proteins (FTP) have been used in vitro to kill CMV infected cells with greater efficiency than antivirals. We investigated the safety and feasibility of the administration of an FTP to human kidneys during normothermic machine perfusion (NMP). Methods Five pairs of human kidneys were recruited into the study. One of each pair was treated with the FTP during NMP and compared to the paired control kidney. Prior to NMP, kidneys were flushed with Ringer’s solution and the effluent from the renal vein collected. Perfusate was also collected after NMP. Cells were isolated, cultured and stained for the CMV specific immediate-early antigen expression. Perfusion parameters, perfusate, urine and tissue samples were collected for assessment of function and injury. Results There was no significant difference in renal perfusate flow [ area under the curve (AUC) control 1196 vs treated 1250 ml/min/100g.h, P=0.791] or intrarenal resistance [AUC control 3.00 vs treated 2.4 mmHg/min/100g.h, P=0.366]. There was also no significant difference in injury markers between the treated and control kidneys (P>0.05). In cells collected from the perfusate, the mean foci of infection did not decrease in the control group but was reduced by 95% in the treated kidneys (P=0.01). Conclusion Treatment for CMV during NMP appeared safe and reduced the foci of infection in cells isolated from the perfusate.