4.6 Article

Supplemental hydrogen sulphide protects transplant kidney function and prolongs recipient survival after prolonged cold ischaemia-reperfusion injury by mitigating renal graft apoptosis and inflammation

Journal

BJU INTERNATIONAL
Volume 110, Issue 11C, Pages E1187-E1195

Publisher

WILEY
DOI: 10.1111/j.1464-410X.2012.11526.x

Keywords

hydrogen sulphide; ischaemia-reperfusion injury; renal transplantation; organ preservation; graft function; survival

Funding

  1. Canadian Urological Association Foundation
  2. American Urological Association Northeastern Section
  3. University of Western Ontario Department of Surgery
  4. Ontario Graduate Studentship Scholarship Award

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OBJECTIVE To characterize the effects of hydrogen sulphide (H2S), 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). MATERIALS AND METHODS After undergoing bilateral native nephrectomy, Lewis rats underwent RTx with kidneys that were flushed with either cold (4 degrees C) standard University of Wisconsin preservation solution (UW) or cold UW + 150 mu M NaHS (H2S) solution and stored for 24 h at 4 degrees 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 H2S-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. H2S-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. CONCLUSION Our results provide the first evidence that supplemental H2S 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.

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