Peter Urbanellis1,2, Matyas Hamar1,3,4, J Moritz Kaths1,2, Dagmar Kollmann1, Ivan Linares1,2, Laura Mazilescu1,2, Sujani Ganesh1, Aryn Wiebe1, Paul M Yip5, Rohan John5, Ana Konvalinka6,7, Istvan Mucsi8, Anand Ghanekar1, Darius J Bagli2,9, Lisa A Robinson2,3,10, Markus Selzner1,2. 1. Multi Organ Transplant Program, Department of Surgery, Toronto General Hospital, University Health Network, Toronto, ON, Canada. 2. Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, ON, Canada. 3. Division of Nephrology, Department of Medicine, The Hospital for Sick Children, Toronto, ON, Canada. 4. Department of Transplantation and Surgery, Semmelweis University, Budapest, Hungary. 5. Multi-Organ Transplant Program, Department of Laboratory Medicine and Pathobiology, Toronto General Hospital, University of Toronto, Toronto, ON, Canada. 6. Department of Medicine and Institute of Medical Science, University of Toronto, Toronto, Canada. 7. Division of Nephrology, Department of Medicine, University Health Network and University of Toronto, Toronto, Canada. 8. Multi Organ Transplant Program, Department of Medicine, University of Toronto, Toronto, ON, Canada. 9. Departments of Surgery (Urology) & Physiology, The Hospital for Sick Children, Toronto, ON, Canada. 10. Program in Cell Biology, The Hospital for Sick Children Research Institute, Toronto, ON, Canada.
Abstract
BACKGROUND: Better preservation strategies for the storage of donation after circulatory death grafts are essential to improve graft function and to increase the kidney donor pool. We compared continuous normothermic ex vivo kidney perfusion (NEVKP) with hypothermic anoxic machine perfusion (HAMP) and static cold storage (SCS) in a porcine kidney autotransplantation model. METHODS: Porcine kidneys were exposed to 30 minutes of warm ischemia and then reimplanted following either 16 hours of either SCS, HAMP (LifePort 1.0), or NEVKP before autotransplantation (n = 5 per group). The contralateral kidney was removed. Animals were followed for 8 days. RESULTS: Grafts preserved by NEVKP demonstrated improved function with more rapid recovery compared with HAMP and SCS (mean peak serum creatinine: 3.66 ± 1.33 mg/dL [postoperative d 1 [(POD1)], 8.82 ± 3.17 mg/dL [POD2], and 12.90 ± 2.19 mg/dL [POD3], respectively). The NEVKP group demonstrated significantly increased creatinine clearance calculated on POD3 (63.6 ± 19.0 mL/min) compared with HAMP (13.5 ± 10.3 mL/min, P = 0.001) and SCS (4.0 ± 2.6 mL/min, P = 0.001). Histopathologic injury scores on POD8 were lower in both perfused groups (NEVKP and HAMP, score: 1-1.5) compared with SCS (score: 1-3, P = 0.3), without reaching statistical significance. CONCLUSIONS: NEVKP storage significantly improved early kidney function compared with both cold preservation strategies, although HAMP also demonstrates improvement over SCS. NEVKP may represent a novel, superior preservation option for donation after circulatory death renal grafts compared with conventional hypothermic methods.
BACKGROUND: Better preservation strategies for the storage of donation after circulatory death grafts are essential to improve graft function and to increase the kidney donor pool. We compared continuous normothermic ex vivo kidney perfusion (NEVKP) with hypothermic anoxic machine perfusion (HAMP) and static cold storage (SCS) in a porcine kidney autotransplantation model. METHODS: Porcine kidneys were exposed to 30 minutes of warm ischemia and then reimplanted following either 16 hours of either SCS, HAMP (LifePort 1.0), or NEVKP before autotransplantation (n = 5 per group). The contralateral kidney was removed. Animals were followed for 8 days. RESULTS: Grafts preserved by NEVKP demonstrated improved function with more rapid recovery compared with HAMP and SCS (mean peak serum creatinine: 3.66 ± 1.33 mg/dL [postoperative d 1 [(POD1)], 8.82 ± 3.17 mg/dL [POD2], and 12.90 ± 2.19 mg/dL [POD3], respectively). The NEVKP group demonstrated significantly increased creatinine clearance calculated on POD3 (63.6 ± 19.0 mL/min) compared with HAMP (13.5 ± 10.3 mL/min, P = 0.001) and SCS (4.0 ± 2.6 mL/min, P = 0.001). Histopathologic injury scores on POD8 were lower in both perfused groups (NEVKP and HAMP, score: 1-1.5) compared with SCS (score: 1-3, P = 0.3), without reaching statistical significance. CONCLUSIONS: NEVKP storage significantly improved early kidney function compared with both cold preservation strategies, although HAMP also demonstrates improvement over SCS. NEVKP may represent a novel, superior preservation option for donation after circulatory death renal grafts compared with conventional hypothermic methods.
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