Here, we report that in response to AKI in the kidney, the activation of Atm and p53 induces Plk2 and p21cip1, which then activates Nrf2 through phosphorylation and recruitment of Nrf2 into the nuclei for the expression of anti-inflammatory factors as well as anti-oxidative regulators. This evidence concerns the gene CDKN1A and acute kidney injury.