Hydrogen Sulfide Treatment Mitigates Donor Tissue Necrosis During Prolonged Cold Storage and Improves Survival Following Allogeneic Renal Transplantation.
1Microbiology and Immunology, Western University Canada, London, ON, Canada
2Pathology, Western University Canada, London, ON, Canada
3Matthew Mailing Centre for Translational Transplant Studies, London Health Sciences Centre, London, ON, Canada
4Surgery, Western University Canada, London, ON, Canada.
Meeting: 2016 American Transplant Congress
Abstract number: C123
Keywords: Graft survival, Kidney, Necrosis, Preservation
Session Information
Session Name: Poster Session C: Ischemia Reperfusion Injury and Organ Preservation
Session Type: Poster Session
Date: Monday, June 13, 2016
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Halls C&D
Organ procurement is inherently associated with ischemia-reperfusion injury (IRI), resulting from loss and subsequent restoration of blood flow, which is detrimental to short- and 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).
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; n=8) or UW + 150 [micro]M NaHS (H2S group; n=5) and stored for 24 hours at 4[deg]C in the same solution. Sham surgeries (midline incision only; n=5) 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 (n=8 per group) were perfused with 5 [micro]M 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.
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.
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.
CITATION INFORMATION: Lobb I, Liu W, Jiang J, Lian D, Sener A. Hydrogen Sulfide Treatment Mitigates Donor Tissue Necrosis During Prolonged Cold Storage and Improves Survival Following Allogeneic Renal Transplantation. Am J Transplant. 2016;16 (suppl 3).
To cite this abstract in AMA style:
Lobb I, Liu W, Jiang J, Lian D, Sener A. Hydrogen Sulfide Treatment Mitigates Donor Tissue Necrosis During Prolonged Cold Storage and Improves Survival Following Allogeneic Renal Transplantation. [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/hydrogen-sulfide-treatment-mitigates-donor-tissue-necrosis-during-prolonged-cold-storage-and-improves-survival-following-allogeneic-renal-transplantation/. Accessed May 9, 2025.« Back to 2016 American Transplant Congress