Ferroptosis in kidney disease.

Kidney disease is a growing global public health concern that is associated with high rates of severe morbidity and mortality. Accumulating preclinical and clinical evidence suggests that ferroptosis, an iron-dependent form of regulated cell death characterized by lethal lipid peroxidation, drives the pathogenesis and progression of diverse kidney disorders, including acute kidney injury, chronic kidney disease, renal cell carcinoma and autosomal-dominant polycystic kidney disease. Ferroptosis of renal tubular epithelial cells and intrarenal immune cells engages complex crosstalk with other regulated cell death pathways, amplifying responses and aggravating renal tissue damage. Several biomarkers of early kidney injury, such as the iron regulator NGAL and the phosphatidylserine-binding protein KIM1, are associated with features of ferroptotic cell death, suggesting their potential utility as indirect indicators of early ferroptotic lesions in the kidney. Furthermore, multimodal imaging platforms that integrate optical, magnetic resonance, photoacoustic and radionuclide techniques enable specific in vivo detection of ferroptotic hallmarks, facilitating early diagnosis of kidney lesions. Numerous preclinical studies have identified a diverse range of synthetic small-molecule agents, natural phytochemicals and metabolic modulators that are able to modify ferroptotic signalling. These agents have been shown to mitigate renal parenchymal injury or suppress the proliferation of malignant kidney cells, robustly establishing ferroptosis as a promising therapeutic target for kidney diseases.