MP06-13 BENEFICAL EFFECT OF HYDROGEN SULFIDE ON RENAL ISCHEMIA-REPERFUSION INJURY IN CLAWN MINIATURE SWINE

Abstract

You have accessJournal of UrologyTransplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery I1 Apr 2017MP06-13 BENEFICAL EFFECT OF HYDROGEN SULFIDE ON RENAL ISCHEMIA-REPERFUSION INJURY IN CLAWN MINIATURE SWINE Yuichi Ariyoshi, Mitsuhiro Sekijima, Takahiro Murokawa, Hisashi Sahara, Motoo Araki, Yasutomo Nasu, and Kazuhiko Yamada Yuichi AriyoshiYuichi Ariyoshi More articles by this author , Mitsuhiro SekijimaMitsuhiro Sekijima More articles by this author , Takahiro MurokawaTakahiro Murokawa More articles by this author , Hisashi SaharaHisashi Sahara More articles by this author , Motoo ArakiMotoo Araki More articles by this author , Yasutomo NasuYasutomo Nasu More articles by this author , and Kazuhiko YamadaKazuhiko Yamada More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.258AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The organ shortage is the major problem in kidney transplantation. To overcome this obstacle, kidney transplants of the marginal donor, cardiac death (DCD) and extended-criteria donors, were increasing. In this setting, the prevention of ischemia-reperfusion injury (IRI) is important for both early and long-term allograft function. Hydrogen Sulfides (H2S) have recently been reported to demonstrate both anti-inflammatory and cytoprotective effects. However, the efficacy and safety of H2S has yet to be elicited in a large animal model. We investigated whether H2S administration was effective for control of renal IRI and optimal administration method in a large animal model. METHODS Female, MHC-inbred, CLAWN miniature swine (n=8) underwent renal ischemia for 120-minutes by occlusion of the left renal artery and vein. Group 1 animals (n=3) underwent renal ischemia exclusively without any additional treatment. Group 2 recipients (n=2) received 1.1 mg/kg of intravenous Na2S 10-minutes prior to kidney reperfusion, followed by an additional 1.1 mg/kg of Na2S 30-minutes post-reperfusion. Group 3 recipients (n=3) underwent selective renal artery administration of 1.1 mg/kg of Na2S 10-minutes prior to reperfusion, followed by an additional 1.1 mg/kg of Na2S 30-minutes post-reperfusion via the supra-renal aorta with concomitant occlusion of the infra-renal aorta, thus allowing for exclusive renal administration. Post-operative renal function was monitored by daily serum creatinine, analysis of circulating cytokine activity (TNF-α, IL-6 and HMGB1) to measure the inflammatory response to IRI and histological evaluation of renal biopsies obtained on post-operative days (POD) 2, 7 and 14. RESULTS H2S administration did not result in any adverse side effects in the recipients. All animals experienced transient acute kidney injury, achieving a peak serum creatinine level by POD 3. Recipients in the untreated group had the higher post-operative serum creatinine level than selective renal H2S administration group (POD4: 4.4 vs 8.6 mg/dl, p<0.001). Pathologically, Control group still showed strongly epithelial flattering and vacuolations, congestion of PTC, and condensed tubular nuclei as a result of influence of IRI. In systemic group, the structures of renal tubule were well preserved comparatively, and those changes in selective group were obviously disappeared. Furthermore, on POD 7, specimens from selective group showed disappointment of IRI change. In selective group, the serum TNF-α and HMGB-1 level was lower than systemic group (TNF-α: 30.6 vs 85.4 pg/ml, p<0.05, HMGB-1: 2.6 vs 11.4 ng/ml, p<0.05). The mRNA expression of IL-1β was also suppressed in selective group specimen. CONCLUSIONS H2S administration performed safety and appeared to have potential cytoprotective and anti-inflammatory effects following renal IRI. This effect was most profound with selective renal artery administration. Further work investigating the benefits of H2S for organ procurement and preservation is warranted as this may allow for improved outcomes following renal transplantation. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e77-e78 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Yuichi Ariyoshi More articles by this author Mitsuhiro Sekijima More articles by this author Takahiro Murokawa More articles by this author Hisashi Sahara More articles by this author Motoo Araki More articles by this author Yasutomo Nasu More articles by this author Kazuhiko Yamada More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...