Is hydrogen sulfide a potential novel therapy to prevent renal damage during ureteral obstruction?

• Published in: Nitric oxide Vol. 73; pp. 15 - 21
• Main Authors: Lin, Shouzhe, Juriasingani, Smriti, Sener, Alp
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 28.02.2018
• Subjects: Animals; Carbon Monoxide - metabolism; Disease Models, Animal; Epithelial-mesenchymal transition; Fibrosis - prevention & control; Gasotransmitters - metabolism; GYY4137; Humans; Hydrogen Sulfide - metabolism; Hydrogen Sulfide - pharmacology; Hydrogen sulphide; Kidney - drug effects; Kidney - physiopathology; Male; Morpholines - pharmacology; Nitric Oxide - metabolism; Organothiophosphorus Compounds - pharmacology; Renal damage; Renal fibrosis; Ureteral Obstruction - etiology; Ureteral Obstruction - physiopathology; Ureteral Obstruction - surgery; Urinary obstruction; Hydrogen sulphide; GYY4137; Epithelial-mesenchymal transition; Renal damage; Renal fibrosis; Urinary obstruction
• ISSN: 1089-8603; 1089-8611
• DOI: 10.1016/j.niox.2017.12.004

In prolonged complete unilateral ureteral obstruction, reduced renal blood flow places the kidney in a state of ischemia, which can cause tubular injury and inflammation. Infiltrating inflammatory cells release transforming growth factor beta 1, which is a cytokine that initiates fibrosis through the epithelial-mesenchymal-transition pathway. Persistent fibrosis can lead to irreversible renal injury and loss of function. While surgical intervention can remove the obstruction, relief of obstruction may not fully reverse renal injury. Additionally, patients often encounter long wait-times between initial consultation and medical intervention, resulting in the accumulation of renal injury that may cause permanent dysfunction. Currently, accepted pharmacological therapies to mitigate the symptoms of ureteral obstruction include acetaminophen, cyclooxygenase-inhibitors, non-steroidal anti-inflammatory medications, opioids and alpha-receptor blockers. However, there is no evidence that they mitigate renal injury. Therefore, identifying potential therapies that could be administered during obstruction may help to improve renal function following decompression. Evidence suggests that endogenously produced gasotransmitters can exhibit anti-inflammatory and antioxidant effects. Nitric oxide, carbon monoxide, and hydrogen sulfide have been identified as gasotransmitters and have been shown to have cytoprotective effects in various models of tissue injury. Studies have shown that treatment with sodium hydrogen sulfide (a hydrogen sulfide donor salt) mitigated transforming growth factor beta 1 expression, oxidative stress, fibrosis, and inflammation associated with urinary obstruction. More recently, the use of more directed hydrogen sulfide donor molecules, such as GYY4137, has led to significant decreases in inflammation, fibrosis, and expression of epithelial mesenchymal transition markers following urinary obstruction. Taken together, these findings suggest that hydrogen sulfide may be a novel potential therapy against renal injury caused by urinary obstruction. This review will highlight the existing literature about the pathogenesis and treatment of renal damage caused by chronic urinary obstruction and propose novel upcoming strategies that could improve patient outcomes. •Chronic ureteral obstruction causes renal damage and loss of renal function.•Removal of obstruction is unlikely to lead to complete renal recovery.•Existing therapeutics are unable to mitigate the accumulation of renal damage.•H2S reduces renal fibrosis and inflammation in renal injury and obstruction models.•Up and coming clinically viable H2S donors may be therapies for urinary obstruction.