Response of the renal epithelium to AKI Response of the renal epithelium to AKI. (1) In response to acute hypoxia or toxic injury, cells within the tubular epithelium undergo cell death. Response of the renal epithelium to AKI. (1) In response to acute hypoxia or toxic injury, cells within the tubular epithelium undergo cell death. Initially regarded as necrosis or apoptosis, this is now known to include a number of other forms of regulated cell death, including anoikis, autophagic cell death, and pyroptosis.31–33 (2) Remaining viable epithelial cells are seen to undergo flattening and have been described as dedifferentiated. Such cells show expression of vimentin but remain E-cadherin positive. (3) Rapid and robust proliferation occurs within the remaining tubular epithelial cells. Recently, this early event has been shown to be accompanied by the expression of the transcription factor Sox9.63,64 This precedes the expression of Pax2, Wnt signaling and Notch signaling within the epithelium. (4) Epithelial cells regain normal polarity and re-establish the tubular histology before returning to a relatively quiescent state. Repeated acute injury as well as chronic injury results in the persistent expression of Wnt and Notch signaling pathways within the epithelium, which results in interstitial fibrosis. Melissa Helen Little, and Pamela Kairath JASN 2017;28:34-46 ©2017 by American Society of Nephrology