Effect of hydrogen sulfide on ischemia-reperfusion injury of kidney: A systematic review and meta-analysis of in vivo animal studies

Hydrogen sulfide (H2S) has been shown to be effective against kidney ischemia-reperfusion injury (IRI) in animal studies. We aimed to evaluate the current evidence from in vivo animal studies for the protective effects of H2S against kidney IRI by systematically reviewing the literature and performing a meta-analysis. Based on the preregistered protocol (PROSPERO: CRD42021295469); PubMed, Medline, Embase, Web of Science, and Scopus were searched to identify in vivo animal studies evaluating the effect of H2S against kidney IRI. Standardized mean difference (SMD) with 95% confidence interval (CI) was calculated and pooled using random-effects meta-analysis. Twenty-two articles complied with eligibility criteria, from which the creatinine levels of 152 control animals and 182 animals treated with H2S from 27 individual experiments were pooled. H2S treatment significantly decreased serum creatinine (SMD = −1.82 [95% CI -1.12, −2.51], p < 0.0001), blood urea nitrogen (−2.50 [-1.46, −3.54], p < 0.0001), tissue malondialdehyde (−2.59 [-3.30, −1.88], p < 0.0001), tunel positive cells (−3.16 [-4.38, −1.94], p < 0.0001), and tubular damage score (−2.01 [-3.03, −0.99], p < 0.0001). There was a high heterogeneity across studies (I2 = 83.5% for serum creatinine level). In meta-regression analysis, the type of H2S donor and its application time accounted for 11.3% (p = 0.025) and 16.6% (p = 0.039) of heterogeneity, respectively. Accordingly, H2S protects the kidney against IRI only if it is given as GYY4137 before or during ischemia. Although H2S is a potential candidate against kidney IRI, further well-designed preclinical studies focusing on GYY4137 are warranted before clinical implication.