Abstract
from loss and subsequent restoration of blood flow, which is detrimental to shortand long-term graft function and survival. Treatment of donor organs with small molecules such as hydrogen sulfide (H2S) is a novel method of modulating prolonged IRI during transplantation. We postulated that H2S treatment during prolonged cold storage could mitigate IRI-induced renal allograft injury following allogeneic renal transplantation (RTx). METHODS: 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 (UWgroup; n1⁄48) or UW+150 mMNaHS (H2Sgroup; n1⁄45) and stored for 24 hours at 4 C in the same solution. Sham surgeries (midline incision only; n1⁄45) were also performed and animals were monitored for 14 days to assess allograft function and survival. An additional subset of donor kidneys in each treatment group (n1⁄48 per group) were perfused with 5 mM Ethidium Homodimer-1 (EthD-1) immediately following cold storage and analyzed via fluorescent microscopy for in situ characterization of tissue necrosis. ATP levels were also measured to assess the metabolic state of donor kidneys following cold storage. RESULTS: H2S treated animals exhibited significantly improved (p<0.05) survival and markedly decreased serum creatinine compared to UW treatment alone. Donor kidneys supplemented with H2S exhibited significantly decreased (p<0.05) EthD-1 staining and markedly improved ATP levels compared to UW treated kidneys immediately following cold storage. CONCLUSIONS: H2S treatment mitigates IRI associated with prolonged cold storage and acutely improves subsequent allograft function and survival. H2S appears to limit tissue necrosis and may maintain cellular metabolism during prolonged cold storage. H2S treatment could represent a novel and cost-effective method of protecting kidneys during transplantation and improving clinical transplant outcomes.
Published Version
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