Mechanisms of regeneration and maladaptive repair in acute kidney injury.

Acute kidney injury (AKI) is a major risk factor for the subsequent development and progression of chronic kidney disease (CKD), particularly when kidney repair is incomplete or maladaptive. The repair trajectory after kidney injury is primarily determined through the interconnected responses of tubular epithelial cells (TECs), immune cells and fibroblasts. Within this network, TECs act as sentinels of tissue injury and initiators of the repair cascade. After AKI, TECs can undergo regulated cell death programs, whereas surviving cells adopt divergent states that either support regeneration or promote maladaptive repair. In successful repair, surviving TECs proliferate, expand and restore tubular integrity. By contrast, failed repair is characterized by persistent cell-cycle arrest, cellular senescence and the secretion of pro-inflammatory and pro-fibrotic mediators. The signals that are released by injured and maladaptively repaired tubules consequently shape the recruitment and activation of immune cells, which can mediate tissue regeneration or perpetuate inflammation and fibroblast activation. Ultimately, aberrant TEC and immune-cell activation converges in the sustained activation of fibroblasts and the deposition of excess extracellular matrix via cellular crosstalk - the common final pathway of maladaptive repair - which drives the progression of AKI to CKD over time.