Hydrogen sulfide protects against cisplatin-induced experimental nephrotoxicity in animal models: a systematic review and meta-analysis.

Abstract

<h4>Background</h4>Cisplatin-induced acute kidney injury (cis-AKI) is not rare in oncological patients clinically, but there are limited prevention and treatment methods available. The efficacy of hydrogen sulfide (H₂S) in mitigating cis-AKI has been studied and determined in animal models.<h4>Methods</h4>According to the pre-registered program (PROSPERO: CRD 42023463779), we searched PubMed/Medline, Embase, and Web of Science databases using the keywords: hydrogen sulfide, cisplatin, acute kidney injury, and alternatives. A total of 13 articles met the inclusion criteria were included. Standardized mean difference (SMD) and 95% confidence interval (CI) were calculated and aggregated using random effects meta-analysis.<h4>Results</h4>The results showed that H₂S treatment significantly improved renal function (serum creatinine SMD = -2.96, 95% CI [-3.72 to -2.19], <i>p</i> < 0.00001; blood urea nitrogen SMD = -2.73, 95% CI [-3.68 to -1.78], <i>p</i> < 0.00001), decreased oxidative stress (superoxide dismutase SMD = 2.90, 95% CI [1.36-4.43], <i>p</i> = 0.0002) and inflammation levels (interleukin-1β SMD = -4.41, 95% CI [-5.84 to -2.97], <i>p</i> < 0.00001). However, there was a high degree of heterogeneity between studies (I² > 70%). Further subgroup analysis did not show a clear source of the heterogeneity, but various H₂S donors exhibited positive renal protection in those studies.<h4>Conclusions</h4>H₂S could be a new approach for treating cis-AKI, while the differential efficacies among natural and slow-release H₂S donors remain to be compared and evaluated further. This meta-analysis may shed light on establishing preclinical and clinical investigation guidelines for treating human cis-AKI with H₂S donors.