S8-3 Hydrogen sulphide: The magic bullet in organ transplantation?

Abstract

Ischemia reperfusion injury (IRI) is unavoidable in renal transplantation and is associated with increased rates of acute tubular necrosis, delayed graft function and impaired early and long-term graft function and survival. Gasotransmitters, particularly H2S, may be cytoprotective in models of IRI in various tissues including the kidney. We aimed to investigate the utility of H2S in mitigating renal IRI during transplantation, thereby improving subsequent renal graft function and survival compared to current standard clinical practices. Our two main objectives were to characterize the real-time protective properties of supplemental H2S against prolonged periods of warm renal IRI as well as determining its protective role in organ preservation during extremes of cold storage and transplantation in murine models. Our results demonstrated, for the first time, that supplemental H2S treatment during prolonged cold ischemia associated with transplantation dramatically improved renal graft survival and function and mitigated graft injury and inflammation compared to grafts that were preserved in standard University of Wisconsin organ preservation solution. In addition, we found that H2S treatment improved real-time renal vascular flow patterns as well as function and decreased the renal injury and inflammation associated with prolonged warm renal IRI. Overall, exogenous H2S may protect kidneys from both prolonged warm and cold IRI associated with renal transplantation. Considering that more transplant centers are utilizing grafts near the limits of cold and warm ischemic times to accommodate their expanding waiting lists, H2S treatment may represent a novel, potent and cost-effective solution to mitigate transplantation induced IRI.