title: Continuous Normothermic Ex Vivo Kidney Perfusion Improves Graft Function in Donation After Circulatory Death Pig Kidney Transplantation.
abstract: BACKGROUND
  Donation after circulatory death (DCD) is current clinical practice to increase the donor pool. Deleterious effects on renal graft function are described for hypothermic preservation. Therefore, current research focuses on investigating alternative preservation techniques, such as normothermic perfusion.
  
  
  METHODS
  We compared continuous pressure-controlled normothermic ex vivo kidney perfusion (NEVKP) with static cold storage (SCS) in a porcine model of DCD autotransplantation. After 30 minutes of warm ischemia, right kidneys were removed from 30-kg Yorkshire pigs and preserved with 8-hour NEVKP or in 4°C histidine-tryptophan-ketoglutarate solution (SCS), followed by kidney autotransplantation.
  
  
  RESULTS
  Throughout NEVKP, electrolytes and pH values were maintained. Intrarenal resistance decreased over the course of perfusion (0 hour, 1.6 ± 0.51 mm per minute vs 7 hours, 0.34 ± 0.05 mm Hg/mL per minute, P = 0.005). Perfusate lactate concentration also decreased (0 hour, 10.5 ± 0.8 vs 7 hours, 1.4 ± 0.3 mmol/L, P < 0.001). Cellular injury markers lactate dehydrogenase and aspartate aminotransferase were persistently low (lactate dehydrogenase < 100 U/L, below analyzer range; aspartate aminotransferase 0 hour, 15.6 ± 9.3 U/L vs 7 hours, 24.8 ± 14.6 U/L, P = 0.298). After autotransplantation, renal grafts preserved with NEVKP demonstrated lower serum creatinine on days 1 to 7 (P < 0.05) and lower peak values (NEVKP, 5.5 ± 1.7 mg/dL vs SCS, 11.1 ± 2.1 mg/dL, P = 0.002). The creatinine clearance on day 4 was increased in NEVKP-preserved kidneys (NEVKP, 39 ± 6.4 vs SCS, 18 ± 10.6 mL/min; P = 0.012). Serum neutrophil gelatinase-associated lipocalin at day 3 was lower in the NEVKP group (1267 ± 372 vs 2697 ± 1145 ng/mL, P = 0.029).
  
  
  CONCLUSIONS
  Continuous pressure-controlled NEVKP improves renal function in DCD kidney transplantation. Normothermic ex vivo kidney perfusion might help to decrease posttransplant delayed graft function rates and to increase the donor pool.
authors.affiliation: 1 Multi Organ Transplant Program, Department of Surgery, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada. 2 Division of Nephrology, The Hospital for Sick Children, Toronto, Ontario, Canada. 3 Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada. 4 Department of General, Visceral, and Transplant Surgery, University Medical Center, Johannes Gutenberg University Mainz, Mainz, Germany. 5 Laboratory Medicine & Pathobiology, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada. 6 Departments of Surgery (Urology) and Physiology, The Hospital for Sick Children, Toronto, Ontario, Canada. 7 Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, Ontario, Canada. 8 Multi Organ Transplant Program, Department of Medicine, University of Toronto, Toronto, Ontario, Canada. 9 Transplant and Regenerative Medicine Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: J Moritz
authors.initials: JM
authors.lastname: Kaths
authors.forename: Juan
authors.initials: J
authors.lastname: Echeverri
authors.forename: Yi Min
authors.initials: YM
authors.lastname: Chun
authors.forename: Jun Yu
authors.initials: JY
authors.lastname: Cen
authors.forename: Nicolas
authors.initials: N
authors.lastname: Goldaracena
authors.forename: Ivan
authors.initials: I
authors.lastname: Linares
authors.forename: Luke S
authors.initials: LS
authors.lastname: Dingwell
authors.forename: Paul M
authors.initials: PM
authors.lastname: Yip
authors.forename: Rohan
authors.initials: R
authors.lastname: John
authors.forename: Darius
authors.initials: D
authors.lastname: Bagli
authors.forename: Istvan
authors.initials: I
authors.lastname: Mucsi
authors.forename: Anand
authors.initials: A
authors.lastname: Ghanekar
authors.forename: David R
authors.initials: DR
authors.lastname: Grant
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Robinson
authors.forename: Markus
authors.initials: M
authors.lastname: Selzner
mesh_terms: D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D050377:Cold Ischemia; D003404:Creatinine / Q000097:blood; D051799:Delayed Graft Function / Q000097:blood / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D005947:Glucose / Q000494:pharmacology; D006085:Graft Survival / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery*; D016030:Kidney Transplantation / Q000009:adverse effects / Q000379:methods*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D000071068:Lipocalin-2 / Q000097:blood; D008297:Male; D008353:Mannitol / Q000494:pharmacology; D023421:Models, Animal; D009392:Nephrectomy; D009926:Organ Preservation / Q000009:adverse effects / Q000379:methods*; D019188:Organ Preservation Solutions / Q000494:pharmacology; D010477:Perfusion / Q000009:adverse effects / Q000379:methods*; D011189:Potassium Chloride / Q000494:pharmacology; D011312:Pressure; D011343:Procaine / Q000494:pharmacology; D012769:Shock; D034421:Sus scrofa; D013997:Time Factors; D014182:Transplantation, Autologous
chemical_list: D015415:Biomarkers; C039984:Bretschneider cardioplegic solution; D000071068:Lipocalin-2; D019188:Organ Preservation Solutions; D019344:Lactic Acid; D008353:Mannitol; D011343:Procaine; D011189:Potassium Chloride; D003404:Creatinine; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D005947:Glucose