Pd56-09 the Effect of the Administration of a Hydrogen Sulfide Donor, Sodium Thiosulfate, in a Rat Acute Kidney Injury Model

You have accessJournal of UrologyTransplantation & Vascular Surgery II (PD56)1 May 2024PD56-09 THE EFFECT OF THE ADMINISTRATION OF A HYDROGEN SULFIDE DONOR, SODIUM THIOSULFATE, IN A RAT ACUTE KIDNEY INJURY MODEL Liam McFarlane, George Dugbartey, Pierce Nelson, Sally Major, Patrick McLeod, Aaron Haig, and Alp Sener Liam McFarlaneLiam McFarlane , George DugbarteyGeorge Dugbartey , Pierce NelsonPierce Nelson , Sally MajorSally Major , Patrick McLeodPatrick McLeod , Aaron HaigAaron Haig , and Alp SenerAlp Sener View All Author Informationhttps://doi.org/10.1097/01.JU.0001008928.01012.0d.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Acute Kidney Injury (AKI) affects 1 in 5 hospitalized adults and is associated with a high mortality rate. Renal ischemia-reperfusion injury (IRI) stands as a prominent cause of AKI. Exogenous hydrogen sulfide administration has been shown to protect against IRI in various organs. In this study, we explore the potential of sodium thiosulfate (STS), a clinically approved hydrogen sulfide donor drug, as a prophylactic or therapeutic treatment for ischemic AKI in a rat model. METHODS: In 10-week-old male rats, ischemic AKI was induced via bilateral renal pedicle occlusion for 60 minutes. At 30 minutes before pedicle occlusion, and/or after 30 minutes of reperfusion, STS was administered at a weigh-based dose to achieve a circulating concentration of 150 µM. Blood and urine samples were collected on postoperative days (POD) 3,5, and 7. At euthanasia (POD3 or POD7), kidneys were harvested for histological analysis. RESULTS: Dual treatment with STS resulted in a noticeable but statistically non-significant preservation of creatinine clearance function after AKI induction (mean serum creatinine ∼200 µmol/L lower than untreated). Pre-treated rats also had improved creatinine clearance as compared to untreated rats, but there was no benefit of post-treatment alone. Dually treated rats exhibited urine concentrating ability statistically similar to sham-operated rats, while all other treatment groups showed decreased urine osmolality on POD 3 and 5 (p<0.05). By POD 7, urine osmolality was statistically similar to sham in all but untreated rats (p<0.002). Kidney tissue from dually treated rats collected on POD3 exhibited a statistically significant decrease in mean percent positive area staining for kidney injury marker 1 (KIM-1) over untreated rats (22% untreated, 10% dual treatment, p<0.05). Pre-treated and post-treated rats also had lower positive staining for these markers (13% and 17%, respectfully), although not statistically significant. CONCLUSIONS: Our findings suggest that STS administration may protect against AKI. A prophylactic approach for AKI is warranted, given recent studies demonstrating the predictability of AKI using machine-learning models and the well-established understanding of AKI induction through procedures like contrast dye administration or transplantation. Treatments with both protective and therapeutic properties would have the potential of both reducing AKI prevalence among hospitalized individuals and the improving outcomes for affected patients. Source of Funding: None © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e1206 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Liam McFarlane More articles by this author George Dugbartey More articles by this author Pierce Nelson More articles by this author Sally Major More articles by this author Patrick McLeod More articles by this author Aaron Haig More articles by this author Alp Sener More articles by this author Expand All Advertisement PDF downloadLoading ...