Hydrogen sulfide protects renal grafts against prolonged cold ischemia‐reperfusion injury via specific mitochondrial actions

Ischemia-reperfusion injury (IRI) is unavoidably caused by loss and subsequent restoration of blood flow during organ procurement and prolonged IRI results in increased rates of delayed graft function and early graft loss. The endogenously produced gasotransmitter, hydrogen sulfide (H2S), is a novel molecule that mitigates hypoxic tissue injury. The current study investigates the protective mitochondrial effects of H2S during in vivo cold storage and subsequent renal transplantation (RTx) and in vitro cold hypoxic renal injury. Donor allografts from Brown Norway rats treated with University of Wisconsin (UW) solution + H2S (150 μM NaSH) during prolonged (24-hour) cold (4°C) storage exhibited significantly (p 1000-fold compared to similar levels of the non-specific H2S donor, GYY4137 and also improved syngraft function and survival following prolonged cold storage compared to UW. H2S treatment mitigates cold IRI-associated renal injury via mitochondrial actions and could represent a novel therapeutic strategy to minimize the detrimental clinical outcomes of prolonged cold IRI during RTx. This article is protected by copyright. All rights reserved.