In this study, we found that cisplatin-induced AKI andrenal tubular apoptosis were accompanied by increased phosphorylation of H2AX and p53,expression of p21, and cleavage of caspase 3, while blocking SET8 by either UNC0379 or itsspecific siRNA inhibited all these responses, suggesting that SET8 mediated DDR contributesto renal epithelial cell death. Here, H2AX is linked to acute kidney injury.