title: Hydrogen Sulfide Treatment Mitigates Renal Allograft Ischemia-Reperfusion Injury during Cold Storage and Improves Early Transplant Kidney Function and Survival Following Allogeneic Renal Transplantation.
abstract: OBJECTIVE
  Ischemia-reperfusion injury is unavoidable during organ transplantation. Prolonged ischemia-reperfusion injury is detrimental to short-term and long-term graft function and survival. H2S is a recently characterized, endogenously produced gaseous molecule with important physiological roles that has been shown to be cytoprotective during tissue ischemia-reperfusion injury. The current study aimed to determine whether H2S could mitigate cold renal ischemia-reperfusion injury in the clinically relevant context of allogeneic renal transplantation.
  
  
  METHODS
  Following bilateral native nephrectomy Lewis rats underwent renal transplantation with kidneys from Brown Norway donor rats that were flushed with cold (4C) standard University of Wisconsin preservation solution (University of Wisconsin preservation solution group) or cold University of Wisconsin preservation solution plus 150 μM NaHS (H2S group) solution. Kidneys were stored for 6 hours at 4C in the same solution. Recipient animals were monitored for 14 days or until sacrifice using metabolic cages to assess various parameters of renal graft function.
  
  
  RESULTS
  H2S treatment improved early allograft survival and function, and decreased early levels of necrosis, apoptosis and Kim-1 compared to University of Wisconsin preservation solution alone. H2S treatment did not affect allograft rejection. Rather, it modulated the early allograft transcriptome to decrease the expression of renal injury, coagulation and cellular stress response genes, and increase the expression of cellular proliferation and Ifn-γ induced genes compared to University of Wisconsin preservation solution alone.
  
  
  CONCLUSIONS
  To our knowledge our findings are the first to show that H2S protects donor kidneys against cold ischemia-reperfusion injury in the context of allogeneic renal transplantation. This potentially represents a novel cost-effective therapeutic solution to mitigate ischemia-reperfusion injury and improve the clinical outcomes of renal transplantation.
authors.affiliation: Department of Microbiology and Immunology, London Health Sciences Center, Western University, London, Ontario, Canada; Matthew Mailing Center for Translational Transplant Studies, London Health Sciences Center, Western University, London, Ontario, Canada.
authors.forename: Ian
authors.initials: I
authors.lastname: Lobb
authors.affiliation: Matthew Mailing Center for Translational Transplant Studies, London Health Sciences Center, Western University, London, Ontario, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Davison
authors.affiliation: Research Institute, London Health Sciences Center, Western University, London, Ontario, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Carter
authors.affiliation: Department of Pathology, London Health Sciences Center, Western University, London, Ontario, Canada.
authors.forename: Weihua
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Pathology, London Health Sciences Center, Western University, London, Ontario, Canada.
authors.forename: Aaron
authors.initials: A
authors.lastname: Haig
authors.affiliation: Department of Microbiology and Immunology, London Health Sciences Center, Western University, London, Ontario, Canada; Multi-Organ Transplant Program, Western University, London Health Sciences Center, Western University, London, Ontario, Canada; Department of Medicine, London Health Sciences Center, Western University, London, Ontario, Canada; Matthew Mailing Center for Translational Transplant Studies, London Health Sciences Center, Western University, London, Ontario, Canada.
authors.forename: Lakshman
authors.initials: L
authors.lastname: Gunaratnam
authors.affiliation: Department of Microbiology and Immunology, London Health Sciences Center, Western University, London, Ontario, Canada; Department of Surgery, London Health Sciences Center, Western University, London, Ontario, Canada; Multi-Organ Transplant Program, Western University, London Health Sciences Center, Western University, London, Ontario, Canada; Matthew Mailing Center for Translational Transplant Studies, London Health Sciences Center, Western University, London, Ontario, Canada. Electronic address: alp.Sener@lhsc.on.ca.
authors.forename: Alp
authors.initials: A
authors.lastname: Sener
mesh_terms: D064591:Allografts; D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D050377:Cold Ischemia; D004195:Disease Models, Animal; D006085:Graft Survival / Q000187:drug effects*; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D053208:Kaplan-Meier Estimate; D016030:Kidney Transplantation; D008297:Male; D009926:Organ Preservation / Q000379:methods*; D055031:Primary Graft Dysfunction / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D059467:Transcriptome / Q000187:drug effects
chemical_list: D006862:Hydrogen Sulfide
keywords: graft survival; hydrogen sulfide; kidney transplantation; reperfusion injury; transcriptome