title: Eight-Hour Continuous Normothermic Ex Vivo Kidney Perfusion Is a Safe Preservation Technique for Kidney Transplantation: A New Opportunity for the Storage, Assessment, and Repair of Kidney Grafts.
abstract: BACKGROUND
  Hypothermic kidney storage causes preservation injury and is poorly tolerated by renal grafts. We investigated whether static cold storage (SCS) can be safely replaced with a novel technique of pressure-controlled normothermic ex vivo kidney perfusion (NEVKP) in heart-beating donor kidney transplantation.
  
  
  METHODS
  Right kidneys were removed from 30 kg Yorkshire pigs in a model of heart-beating donation and either preserved in cold histidine-tryptophan-ketoglutarate solution for 8 hours (n = 5), or subjected to 8 hours of pressure-controlled NEVKP (n = 5) followed by renal heterotopic autotransplantation.
  
  
  RESULTS
  During NEVKP, physiologic perfusion conditions were maintained with low intrarenal resistance and normal electrolyte and pH parameters. Aspartate aminotransferase and lactate dehydrogenase as injury markers were below the detectable analyzer range (<4 and <100 U/L, respectively). Perfusate lactate concentration decreased from baseline until the end of perfusion (10.38 ± 0.76 mmol/L vs 1.22 ± 0.26 mmol/L; P < 0.001). Posttransplantation, animals transplanted with NEVKP versus SCS grafts demonstrated similar serum creatinine peak levels (NEVKP, 2.0 ± 0.5 vs SCS 2.7 ± 0.7 mg/dL; P = 0.11) and creatinine clearance on day 10 (NEVKP, 65.9 ± 18.8 mL/min vs SCS 61.2 ± 15.6 mL/min; P = 0.74). After 10 days of follow-up, animals transplanted with NEVKP grafts had serum creatinine and blood urea nitrogen values comparable to their basal levels (P = 0.49 and P = 0.59), whereas animals transplanted with SCS grafts had persistently elevated serum creatinine and blood urea nitrogen when compared with basal levels (P = 0.01 and P = 0.03).
  
  
  CONCLUSIONS
  Continuous pressure-controlled NEVKP is feasible and safe in good quality heart-beating donor kidney grafts. It maintains a physiologic environment and excellent graft function ex vivo during preservation without causing graft injury.
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 Transplantation Surgery, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstr, Mainz, Germany. 5 Programa de Doctorat en Medicina de la Universitat Autònoma de Barcelona, Barcelona, Spain. 6 Laboratory Medicine and Pathobiology, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada. 7 Departments of Surgery (Urology) & Physiology, The Hospital for Sick Children, Toronto, Ontario, Canada. 8 Developmental and Stem Cell Biology, 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: Nicolas
authors.initials: N
authors.lastname: Goldaracena
authors.forename: Kristine S
authors.initials: KS
authors.lastname: Louis
authors.forename: Yi-Min
authors.initials: YM
authors.lastname: Chun
authors.forename: Ivan
authors.initials: I
authors.lastname: Linares
authors.forename: Aryn
authors.initials: A
authors.lastname: Wiebe
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Foltys
authors.forename: Paul M
authors.initials: PM
authors.lastname: Yip
authors.forename: Rohan
authors.initials: R
authors.lastname: John
authors.forename: Istvan
authors.initials: I
authors.lastname: Mucsi
authors.forename: Anand
authors.initials: A
authors.lastname: Ghanekar
authors.forename: Darius J
authors.initials: DJ
authors.lastname: Bagli
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 / Q000378:metabolism; D001806:Blood Urea Nitrogen; D050377:Cold Ischemia / Q000009:adverse effects; D003404:Creatinine / Q000097:blood; D005240:Feasibility Studies; D005947:Glucose / Q000494:pharmacology; D006085:Graft Survival; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D016030:Kidney Transplantation / Q000009:adverse effects / Q000379:methods*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; 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; D011189:Potassium Chloride / Q000494:pharmacology; D011312:Pressure; D011343:Procaine / Q000494:pharmacology; D034421:Sus scrofa; D013997:Time Factors; D014022:Tissue Survival; D014182:Transplantation, Autologous
chemical_list: D015415:Biomarkers; C039984:Bretschneider cardioplegic solution; 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