Reciprocally, SIRT1 acted as a delactylase delactylase to reduce H3K18la and inhibit SPHK1 transcription, forming a SPHK1-SIRT1 negative feedback loop.<h4>Conclusions</h4>The study identifies an H3K18la-mediated SPHK1-SIRT1 axis as a key factor of RTEC pyroptosis in SA-AKI. Here, SPHK1 is linked to acute kidney injury.