title: Continuous Normothermic Ex Vivo Kidney Perfusion Is Superior to Brief Normothermic Perfusion Following Static Cold Storage in Donation After Circulatory Death Pig Kidney Transplantation.
abstract: Hypothermic preservation is known to cause renal graft injury, especially in donation after circulatory death (DCD) kidney transplantation. We investigated the impact of cold storage (SCS) versus short periods of normothermic ex vivo kidney perfusion (NEVKP) after SCS versus prolonged, continuous NEVKP with near avoidance of SCS on kidney function after transplantation. Following 30 min of warm ischemia, kidneys were removed from 30-kg Yorkshire pigs and preserved for 16 h with (A) 16 h SCS, (B) 15 h SCS + 1 h NEVKP, (C) 8 h SCS + 8 h NEVKP, and (D) 16 h NEVKP. After contralateral kidney resection, grafts were autotransplanted and pigs followed up for 8 days. Perfusate injury markers such as aspartate aminotransferase and lactate dehydrogenase remained low; lactate decreased significantly until end of perfusion in groups C and D (p < 0.001 and p = 0.002). Grafts in group D demonstrated significantly lower serum creatinine peak when compared to all other groups (p < 0.001) and 24-h creatinine clearance at day 3 after surgery was significantly higher (63.4 ± 19.0 mL/min) versus all other groups (p < 0.001). Histological assessment on day 8 demonstrated fewer apoptotic cells in group D (p = 0.008). In conclusion, prolonged, continuous NEVKP provides superior short-term outcomes following DCD kidney transplantation versus SCS or short additional NEVKP following SCS.
authors.affiliation: Multi Organ Transplant Program, Department of Surgery, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.|Division of Nephrology, The Hospital for Sick Children, Toronto, Ontario, Canada.|Department of General, Visceral, and Transplant Surgery, University Medical Center Mainz, Mainz, Germany.
authors.forename: J M
authors.initials: JM
authors.lastname: Kaths
authors.affiliation: Division of Nephrology, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: J Y
authors.initials: JY
authors.lastname: Cen
authors.affiliation: Multi Organ Transplant Program, Department of Surgery, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
authors.forename: Y M
authors.initials: YM
authors.lastname: Chun
authors.affiliation: Multi Organ Transplant Program, Department of Surgery, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Echeverri
authors.affiliation: Multi Organ Transplant Program, Department of Surgery, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
authors.forename: I
authors.initials: I
authors.lastname: Linares
authors.affiliation: Multi Organ Transplant Program, Department of Surgery, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Ganesh
authors.affiliation: Laboratory Medicine & Pathobiology, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada.
authors.forename: P
authors.initials: P
authors.lastname: Yip
authors.affiliation: Laboratory Medicine & Pathobiology, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada.
authors.forename: R
authors.initials: R
authors.lastname: John
authors.affiliation: Departments of Surgery (Urology) & Physiology, The Hospital for Sick Children, Toronto, Ontario, Canada.|Developmental & Stem Cell Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Bagli
authors.affiliation: Multi Organ Transplant Program, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: I
authors.initials: I
authors.lastname: Mucsi
authors.affiliation: Multi Organ Transplant Program, Department of Surgery, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Ghanekar
authors.affiliation: Multi Organ Transplant Program, Department of Surgery, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
authors.forename: D R
authors.identifier: 0000-0003-4468-8276
authors.initials: DR
authors.lastname: Grant
authors.affiliation: Division of Nephrology, The Hospital for Sick Children, Toronto, Ontario, Canada.|Program in Cell Biology, The Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.
authors.forename: L A
authors.initials: LA
authors.lastname: Robinson
authors.affiliation: Multi Organ Transplant Program, Department of Surgery, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Selzner
mesh_terms: D000818:Animals; D001926:Brain Death; D003080:Cold Temperature; D016030:Kidney Transplantation / Q000379:methods*; D008297:Male; D009926:Organ Preservation / Q000379:methods*; D010477:Perfusion; D034421:Sus scrofa; D020858:Tissue and Organ Harvesting / Q000379:methods / Q000592:standards*; D009927:Tissue and Organ Procurement
keywords: animal models: porcine; autotransplantation; basic (laboratory) research/science; donors and donation: donation after circulatory death (DCD); kidney transplantation/nephrology; organ perfusion and preservation; organ transplantation in general; regenerative medicine; tissue injury and repair; translational research/science