Comparison of Continuous Normothermic Ex Vivo Kidney Perfusion to Dynamic and Static Hypothermic Preservation Techniques in Porcine Kidneys Donated after Cardiac Death
Matyas Hamar1,2, Peter Urbanellis1, Dagmar Kollmann1, Ivan Linares1, Sujani Ganesh1, Roizar Rosales1, Istvan Mucsi1, Ana Konvalinka3, Darius Bagli4, Anand Ghanekar1, Moritz Kaths1, Paul Yip5, Rohan John5, Lisa Robinson2, Markus Selzner1.
1Multi Organ Transplant Program, UHN Toronto General Hospital, Toronto, ON, Canada; 2Division of Nephrology, The Hospital for Sick Children, Toronto, ON, Canada; 3Department of Medicine and and Institute of Medical science, University of Toronto, Toronto, ON, Canada; 4Department of surgery (Urology) & Physiology, The Hospital of sick Children, Toronto, ON, Canada; 5Laboratory Medicine and Pathology , Toronto General Hospital, Toronto, ON, Canada
Background: Strategies to decrease preservation-related injury in renal grafts donated after circulatory death (DCD) urgently needed. This highlights the importance of direct comparison of dynamic preservation technologies for kidneys. Our prior work has suggested superior graft function of continuous normothermic ex vivo kidney perfusion (NEVKP) over static cold storage. Here we investigated whether NEVKP could promote functional recovery compared to hypothermic machine perfusion (HMP).
Methods: 15 porcine kidneys were exposed to 30min of warm ischemia, then subjected to either 16hrs of SCS, 16hrs of HMP (LifePort® 1.0) or 16hrs of NEVKP prior to autotransplantation (n=5 each group). Animals were followed for 8 days. Graft function and histology were assessed.
Results: Grafts preserved by NEVKP demonstrated improved graft function, and more rapid graft recovery, with the mean peak serum creatinine of 3.66 ± 1.33mg/dl, occurring on day 1, compared with 8.82 ± 3.17mg/dl in the HMP group, occurring on day 2, and 10.5 ± 5.38mg/dl in the SCS group, occurring on day 3. Differences between daily serum creatinine levels reached significance between NEVKP and HMP on day 1 (p=0.002), day 2 (p=0.004) and day 3 (p=0.024), and between HMP and SCS on day 3 (p=0.016) and day 4 (p=0.046). 
Injury scores [scaled from 0 to 3] were lower in both perfused groups (NEVKP, HMP): score: 1 (1-1.5) compared to SCS group: score: 1.5(1-3) in wedge biopsies taken on postoperative day 8, however this did not reach statistical significance (p>0.05). Similarly, inflammation scores were not statistically different between any groups.
Conclusion: In this DCD model of renal autotransplantation, we demonstrated that NEVKP significantly improved initial graft function compared to either HMP or SCS. Thus, normothermic perfusion may provide superior preservation options for DCD renal grafts than conventional hypothermic methods. The biologic mechanisms underlying normothermic preservation present new opportunities to advance these findings.
