How much can the tubule regenerate and who does it? An open question

The tubular compartment of the kidney is the primary site of a wide range of insults that can result in acute kidney injury (AKI), a condition associated with high mortality and an increased risk to develop end-stage renal disease. Nevertheless, kidney function is often quickly recovered after tubular injury. How this happens has only partially been unveiled. Indeed, although it has clearly been demonstrated that regenerated epithelial cells arise from survived intratubular cells, the true entity, as well as the cellular source of this regenerative process, remains mostly unknown. Is whichever proximal tubular epithelial cell able to dedifferentiate and divide to replace neighboring lost tubular cells, thus suggesting an extreme regenerative ability of residual tubular epithelium, or is the regenerative potential of tubular epithelium limited, and mostly related to a preexisting population of intratubular scattered progenitor cells which are more resistant to death? Gaining insights on how this process takes place is essential for developing new therapeutic strategies to prevent AKI, as well as AKI-related chronic kidney disease. The aim of this review is to discuss why the answers to these questions are still open, and how further investigations are needed to understand which is the true regenerative potential of the tubule and who are the players that allow functional recovery after AKI.