〔Abstract〕 Objective To observe the effect of Methyltransferase like 3(METTL3) in cisplatin-induced acute kidney injury(AKI) in mice with hyperuricemia.Methods C57BL/6 mice were randomly divided into control group,hyperuricemia group,AKI group,and hyperuricemia+AKI group.The hyperuricemia model was established by injecting with gavage potassium oxyzinate and adenine for 21 days,and the AKI model was established by intraperitoneal injection of cisplatin for 3 days.Serum creatinine,urea nitrogen,blood uric acid,the pathological staining of HE and Masson were detected.The expression of alpha-smooth muscle actin(α-SMA),Kim-1 and METTL3 proteins were detected by Western blot.qPCR detected mRNA changes such as interleukin-6(IL-6),tumor necrosis factor(TNF-α),and IL-1β.The m6A assay detected overall methylation levels in mice.Results Compared with the AKI group alone,the serum creatinine,urea nitrogen and blood uric acid in the hyperuricemia+AKI group significantly increased.Pathological staining,Western blot,and qPCR also showed worsening of renal fibrosis and elevated METTL3 expression in the composite model group.The m6A test results showed that the overall methylation level of mice in the experimental group increased,and the composite model group was significantly higher than that in the AKI group.In vitro experiments,the METTL3-specific inhibitor STM2457 was given to effectively reduce the injury of renal tubular epithelial cells and reduce the level of inflammation and fibrosis.Conclusion Cisplatin can exacerbate renal inflammation and fibrosis caused by high uric acid;STM2457 has therapeutic effects in hyperuricemic nephropathy and cisplatin-induced acute kidney injury,and METTL3 may be a potential target for the treatment of related kidney injury.