Thiosulfate in the form of sodium thiosulfate (STS) is a major oxidation product of hydrogen sulfide (H₂S), an endogenous signaling molecule and the third member of the gasotransmitter family. STS is currently used in the clinical treatment of acute cyanide poisoning, cisplatin toxicities in cancer therapy, and calciphylaxis in dialysis patients. Burgeoning evidence show that STS has antioxidant and anti-inflammatory properties, making it a potential therapeutic candidate molecule that can target multiple molecular pathways in various diseases and drug-induced toxicities. This review discusses the biochemical and molecular pathways in the generation of STS from H₂S, its clinical usefulness, and potential clinical applications, as well as the molecular mechanisms underlying these clinical applications and a future perspective in kidney transplantation.

Ischemia-reperfusion injury is unavoidable during organ transplantation. Prolonged ischemia-reperfusion injury is detrimental to short-term and long-term graft function and survival. H2S is a recently characterized, endogenously produced gaseous molecule with important physiological roles that has been shown to be cytoprotective during tissue ischemia-reperfusion injury. The current study aimed to determine whether H2S could mitigate cold renal ischemia-reperfusion injury in the clinically relevant context of allogeneic renal transplantation. Following bilateral native nephrectomy Lewis rats underwent renal transplantation with kidneys from Brown Norway donor rats that were flushed with cold (4C) standard University of Wisconsin preservation solution (University of Wisconsin preservation solution group) or cold University of Wisconsin preservation solution plus 150 μM NaHS (H2S group) solution. Kidneys were stored for 6 hours at 4C in the same solution. Recipient animals were monitored for 14 days or until sacrifice using metabolic cages to assess various parameters of renal graft function. H2S treatment improved early allograft survival and function, and decreased early levels of necrosis, apoptosis and Kim-1 compared to University of Wisconsin preservation solution alone. H2S treatment did not affect allograft rejection. Rather, it modulated the early allograft transcriptome to decrease the expression of renal injury, coagulation and cellular stress response genes, and increase the expression of cellular proliferation and Ifn-γ induced genes compared to University of Wisconsin preservation solution alone. To our knowledge our findings are the first to show that H2S protects donor kidneys against cold ischemia-reperfusion injury in the context of allogeneic renal transplantation. This potentially represents a novel cost-effective therapeutic solution to mitigate ischemia-reperfusion injury and improve the clinical outcomes of renal transplantation.

Ischemia–reperfusion injury is unavoidably caused by loss and subsequent restoration of blood flow during organ procurement, and prolonged ischemia–reperfusion injury 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-h) cold (4°C) storage exhibited significantly (p < 0.05) decreased acute necrotic/apoptotic injury and significantly (p < 0.05) improved function and recipient Lewis rat survival compared to UW solution alone. Treatment of rat kidney epithelial cells (NRK-52E) with the mitochondrial-targeted H₂S donor, AP39, during in vitro cold hypoxic injury improved the protective capacity of H₂S >1000-fold compared to similar levels of the nonspecific H₂S donor, GYY4137 and also improved syngraft function and survival following prolonged cold storage compared to UW solution. 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.

Introduction: The incidence of renal cell carcinoma (RCC) continues to rise concurrently with the increased prevalence of end-stage renal disease worldwide. Treatment for small renal masses continues to be partial nephrectomy mostly involving the clamping of renal blood vessels. Although necessary, this technique results in warm renal ischemia and reperfusion injury (IRI) to the afflicted kidney. We have recently demonstrated that hydrogen sulfide (H2S), a novel endogenous gaseous molecule, protects against prolonged cold and short-term warm renal IRI. In the current study, we examined whether exogenous H2S has long-term protective effects against warm renal IRI associated with renal surgical procedures.Methods: Uni-nephrectomized Lewis rats underwent 1 hour of warm ischemia induced by clamping of the renal pelvis. Animals underwent either intraperitoneal treatment with phosphate buffered saline (PBS; IRI group) or PBS supplemented with 150 μM NaHS (H2S group), and were compared against Sham-operated rats.Results: H2S treatment improved long-term renal function as serum creatinine at day 7 was significantly decreased in the H2S group compared to IRI animals (p < 0.05). H2S treatment decreased the expression of pro-inflammatory markers TLR-4, TNF-α, IFNγ, IL-2and ICAM-1, increased the expression of pro-survival molecule Bcl-2 and decreased the expression of pro-apoptotic marker BID at postoperative day 1. H2S-treated kidneys also showed a significant decrease (p < 0.05) in infiltration of macrophages at day 7 post-IRI compared to no treatment.Conclusion: H2S treatment improved long-term renal function and decreased long-term inflammation associated with warm IRI, and may offer a novel therapeutic approach to preventing warm IRI-induced renal injury associated with renal surgical procedures.

Erroneous and delayed triage in an increasingly crowded emergency department (ED). ChatGPT is an artificial intelligence model developed by OpenAI^® and is being trained for use in natural language processing tasks. Our study aims to determine the accuracy of patient triage using ChatGPT according to the emergency severity index (ESI) for triage in EDs. In our cross-sectional study, 18 years and over patients who consecutively presented to our ED within 24 h were included. Age, gender, admission method, chief complaint, state of consciousness, and comorbidities were recorded on the case form, and the vital signs were detected at the triage desk. A five-member expert committee (EC) was formed from the fourth-year resident physicians. The investigators converted real-time patient information into a standardized case format. The urgency status of the patients was evaluated simultaneously by EC and ChatGPT according to ESI criteria. The median value of the EC decision was accepted as the gold standard. There was a statistically significant moderate agreement between EC and ChatGPT assessments regarding urgency status (Cohen’s Kappa = 0.659; P < 0.001). The accuracy between these two assessments was calculated as 76.6%. There was a high degree of agreement between EC and ChatGPT for the prediction of ESI-1 and 2, indicating high acuity (Cohen’s Kappa = 0.828). The diagnostic specificity, NPV, and accuracy of ChatGPT were determined as 95.63, 98.17 and 94.90%, respectively, for ESI high acuity categories. Our study shows that ChatGPT can successfully differentiate patients with high urgency. The findings are promising for integrating artificial intelligence-based applications such as ChatGPT into triage processes in EDs.