In this study, we report that in response to AKI, the activation of Atm and p53 elicits the expression of Plk2/p21cip1, which activates Nrf2 through phosphorylation by Plk2 and recruitment of Nrf2 by p21cip1 into the nuclei for expression of anti-oxidative and anti-inflammatory factors in response to AKI. Here, CDKN1A is linked to acute kidney injury.