About 28.5% of the acute kidney injury (AKI) patients cannot recover completely. AKI has become an important risk factor for chronic kidney disease (CKD). It has been reported that the activation of YAP facilitates the recovery of AKI, however, this experiment demonstrated that the activation of YAP may last to the post-acute phase of AKI. The persistent activation of YAP is implicated with renal deterioration and fibrosis. Reprogramming factor KLF4 was responsible for the persistent activation of YAP. Shutting down the KLF4-related persistent activation of YAP after acute phase of AKI might be a way to prevent the transition of AKI into CKD.