Tubular Cell Polyploidy and AKI-to-CKD Transition

Episodes of AKI are a major driver of CKD, which is a growing global health challenge that sometimes remains undetected until advanced stages of kidney disease. To compensate for nephron loss, the kidney relies on tubular cell (TC) hypertrophy to maintain function. A crucial adaptive mechanism recently identified in this process is TC polyploidization, which helps mitigate irreversible TC loss during AKI. Polyploid TCs acquire extra genome copies through alternative cell cycles, allowing them to sustain kidney function under stress. However, although polyploidization provides short-term protection, its persistent activation promotes DNA damage, p21 upregulation, and fibrosis, ultimately accelerating CKD progression.