High-throughput drugs screening was conducted to identify candidates acting on the Sphingosine kinase 1(SPHK1)/Sirtuin 1(SIRT1) axis, which were validated <i>in vitro</i> and <i>in vivo</i>.<h4>Results</h4>Lactate aggravated SA-AKI by promoting RTEC pyroptosis. Here, SIRT1 is linked to acute kidney injury.