This study established the potential involvement of the RIPK-3/MLKL necroptotic pathway, oxidative stress, and inflammation in the pathogenesis of renal fibrosis during the UUO model, whereas pretreatment of UUO rats with SOF and/or EDV attenuated renal impairments and ameliorated renal oxidative damage, inflammation, reduced tissue injury, and fibrosis. Here, MLKL is linked to renal fibrosis.