title: Supplemental hydrogen sulphide protects transplant kidney function and prolongs recipient survival after prolonged cold ischaemia-reperfusion injury by mitigating renal graft apoptosis and inflammation.
abstract: What's known on the subject? and What does the study add? Hydrogen sulphide (H(2) S) has recently been classified as a member of the family of small gaseous molecules called gasotransmitters and has been found to have many important physiological functions. Several recent studies have elucidated the protective effects of H(2) S in many models of tissue ischaemia-reperfusion injury (IRI), including hepatic, myocardial, pulmonary, cerebral and renal IRI. It has previously been shown that H(2) S has a number of properties that may contribute to its protection against IRI, including vasodilatory, anti-apoptotic, anti-inflammatory and anti-oxidant effects, although the specific actions appear to vary between tissues. The few studies investigating the effects of H(2) S against renal IRI have only involved clamping of the renal pedicle to induce warm IRI. This study investigated the protective effects of H(2) S in the context of renal transplantation (RTx), which generally involves a more severe period of prolonged cold IRI. A previous study investigated the actions of H(2) S in RTx, but it was performed ex vivo and did not involve actual transplantation of donor kidneys. To our knowledge, this is the first study using a clinically relevant model of RTx to show that treatment of donor kidneys with H(2) S during preservation is protective against prolonged cold IRI. These findings suggest that H(2) S has potential utility in improving clinical organ preservation techniques and increasing the overall success of organ transplantation.
  
  
  OBJECTIVE
  • To characterize the effects of hydrogen sulphide (H(2) S), an endogenously produced molecule recently described to have protective effects against warm ischaemic tissue injury, in mitigating transplantation-associated prolonged cold ischaemia-reperfusion injury (IRI) in a clinically applicable in vivo model of renal transplantation (RTx).
  
  
  METHODS
  • After undergoing bilateral native nephrectomy, Lewis rats underwent RTx with kidneys that were flushed with either cold (4 °C) standard University of Wisconsin preservation solution (UW) or cold UW + 150 µM NaHS (H(2) S) solution and stored for 24 h at 4 °C in the same solution. • Recipient rats were monitored for a 14-day time course using metabolic cages to assess various characteristics of renal graft function. • Renal grafts were removed at time of death or after the rats were killed for histological, immunohistochemical and quantitative PCR analysis.
  
  
  RESULTS
  • H(2) S-treated rats exhibited immediate and significant (P < 0.05) decreases in serum creatinine levels, increased urine output and increased survival compared with UW-treated rats. • H(2) S-treated grafts showed significantly reduced glomerular and tubular necrosis and apoptosis, diminished graft neutrophil and macrophage infiltrates and a trend towards improved inflammatory and anti-apoptotic cytokine profiles.
  
  
  CONCLUSIONS
  • Our results provide the first evidence that supplemental H(2) S can mitigate renal graft IRI incurred during transplantation and prolonged cold storage, improving early graft function and recipient survival in a clinically applicable model of RTx.
authors.affiliation: Departments of Microbiology and Immunology, University of Western Ontario, London, ON, Canada.
authors.forename: Ian
authors.initials: I
authors.lastname: Lobb
authors.forename: Amy
authors.initials: A
authors.lastname: Mok
authors.forename: Zhu
authors.initials: Z
authors.lastname: Lan
authors.forename: Weihua
authors.initials: W
authors.lastname: Liu
authors.forename: Bertha
authors.initials: B
authors.lastname: Garcia
authors.forename: Alp
authors.initials: A
authors.lastname: Sener
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D019587:Dietary Supplements; D004195:Disease Models, Animal; D006085:Graft Survival / Q000187:drug effects*; D006862:Hydrogen Sulfide / Q000008:administration & dosage*; D007249:Inflammation / Q000473:pathology / Q000517:prevention & control*; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000601:surgery; D016030:Kidney Transplantation; D008297:Male; D009926:Organ Preservation / Q000379:methods*; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*
chemical_list: D006862:Hydrogen Sulfide