Hypoxia during the postnatal period represents a significant risk factor for renal injury in neonates, yet the molecular mechanisms linking oxygen deprivation to kidney damage remain unclear. In this study, we explored whether ferroptosis serves as a key mediator in hypoxia-induced acute kidney injury (AKI). Using a neonatal rat model, we demonstrated that hypoxic exposure disrupts iron homeostasis, leading to iron accumulation and excessive lipid peroxidation in renal tissues. These alterations were associated with marked tubular injury, glomerular damage, and progressive fibrotic remodeling. Importantly, reoxygenation attenuated ferroptosis-related signaling pathways and improved renal structural and functional outcomes, although incomplete recovery was observed in fibrotic changes. Our findings suggest that ferroptosis is not only involved in the initiation of hypoxia-induced renal injury but may also contribute to its progression toward chronic kidney pathology. Targeting ferroptosis and iron metabolism may therefore represent a promising strategy for preventing or treating neonatal hypoxia-related AKI.
Liu et al. (Mon,) studied this question.