Renoprotective Effects of AdipoRon in Preclinical Models of Renal Injury: A Systematic Review and Meta-Analysis.

BACKGROUND: AdipoRon has shown promising metabolic and anti-inflammatory effects by activating the AMPK and PPARα pathways. However, its renal effects have not been systematically assessed. This study aimed to evaluate the efficacy of AdipoRon in mitigating renal injury based on preclinical evidence. METHODS: A comprehensive systematic literature search was conducted in accordance with the PRISMA 2020 guidelines. We searched PubMed, Embase, Web of Science, Scopus, and Cochrane Central for publications up to December 2025. The SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) tool was used to evaluate the risk of bias of the included studies. Quantitative synthesis was performed using RevMan 5.4.1, employing standardized mean differences (SMDs) with 95% confidence intervals (CIs) under random-effects models. Heterogeneity was assessed using the I 2 statistic. RESULTS: Eight studies met the inclusion criteria for qualitative synthesis, and four provided extractable data for meta-analysis. AdipoRon significantly reduced albuminuria (SMD = -2.64, 95% CI -3.41 to -1.87, p < 0.001) and triglyceride levels (SMD = -1.65, 95% CI -2.28 to -1.01, p < 0.001) with negligible heterogeneity. Mechanistic analyses indicated that AdipoRon attenuated oxidative stress, inflammation, apoptosis, and fibrosis by activating the AMPK and PPARα signalling pathways. CONCLUSIONS: AdipoRon demonstrated consistent nephroprotective effects in preclinical models, primarily through metabolic and anti-inflammatory modulation. Despite heterogeneity in some outcomes, findings support its potential as a candidate for renal protection. Further standardized and translational studies are needed to confirm these effects in clinical settings.