Kidney Development and Injury: A Road to Regeneration

Proximal tubular epithelial cells (PTECs) are the major cellular targets of acute kidney injury (AKI). PTECs, as well as epithelial cells in glomeruli and distal tubules, are derived from nephron progenitors that exist in the embryonic kidney. However, nephron progenitors disappear around birth by terminal differentiation, meaning that mechanisms of repair following AKI will be different from those during development. Although some developmental genes are re-expressed in experimental AKI models, most PTECs are replaced by surviving mature epithelial cells and the functions of genes in these cells can differ from their developmental functions. Recent progresses in stem cell biology have enabled in vitro generation of kidney organoids from human-induced pluripotent stem cells (iPSCs), and the PTECs in the organoids exhibit some functional features. However, kidney organoids are immature and selective PTEC induction has not been established. In this chapter, we discuss the recent findings regarding AKI from the viewpoint of developmental nephrology and the hurdles to overcome in the treatment of AKI and eventual kidney failure.