P31 Hydrogen sulfide treatment improves graft function and survival following prolonged cold ischemia and allogeneic renal transplantation

Abstract

Organ procurement is inherently associated with ischemia–reperfusion injury (IRI), resulting from loss and subsequent restoration of blood flow, and is detrimental to graft function and survival. Treatment of donor organs with small molecules such as hydrogen sulfide (H 2 S) may be a novel method of mitigating IRI during transplantation. We postulated that H 2 S treatment could mitigate IRI during cold organ storage and subsequent genetically mismatched (allogeneic) renal transplantation (RTx), improving allograft function and survival. Following bilateral native nephrectomy, recipient Lewis rats underwent RTx with kidneys obtained from Brown Norway donor rats that were flushed with either University of Wisconsin preservation solution (UW group) or UW + H 2 S (150 μM NaHS; H 2 S group) and stored for 24 h at 4°C in the same solution. Serum was obtained on subsequent post-operative (PO) days and creatinine was used as a surrogate marker of graft function. H 2 S treated animals exhibited significantly improved survival compared to UW animals ( p < 0.01), with UW animals exhibiting 0% survival by PO day 4 and H 2 S treated animals retaining 20% survival by PO day 14 (end of time course). As well, UW treated animals exhibited markedly increased serum creatinine levels at both PO days 2 and 4 compared to H 2 S animals. These findings indicate that H 2 S treatment can mitigate graft injury following prolonged periods of cold IRI, improving initial graft function and possibly delaying graft rejection. H 2 S treatment could represent a novel method of mitigating IRI during transplantation, thereby improving clinical outcomes.