Ferroptosis in Chronic Kidney Disease: Molecular Mechanisms andTherapeutic Targets

Chronic kidney disease is associated with high incidence and mortality rates and has emerged as a major global public health challenge. However, effective therapeutic strategies to improve patient survival remain limited. Ferroptosis, a regulated form of cell death driven by irondependent lipid peroxidation, has recently emerged as a key contributor to the pathogenesis and progression of chronic kidney disease. Owing to its high mitochondrial density and intense metabolic activity, the kidney is particularly vulnerable to ferroptosis. Accumulating evidence indicates that ferroptosis-mediated cellular damage promotes renal functional decline, whereas ferroptosis inhibitors and iron chelators confer renoprotection across multiple experimental models, highlighting ferroptosis as a promising therapeutic target in kidney diseases. Despite growing interest, the precise pathogenic mechanisms of ferroptosis in the kidney remain incompletely understood. To advance mechanistic insights and therapeutic development, this review summarizes the key molecular events associated with iron overload and lipid peroxidation, as well as their crosstalk with pro-fibrotic and pro-inflammatory signaling pathways. We highlight major regulatory factors, including TFR1, GPX4, FSP1, CHAC1, Nrf2, DHODH, and NLRP3, alongside recent advances in small-molecule modulators targeting these pathways. We also discuss newly identified ferroptosis-related biomarkers that may serve as potential diagnostic or therapeutic indicators. Overall, ferroptosis represents a promising therapeutic avenue for CKD; further studies are required to elucidate its regulatory networks and facilitate clinical translation.