GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE347nnn/GSE347117/primaryOK200TranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE347117GEOGSEfalseFDX1-mediated disulfidptosis drives progression of sepsis-associated AKIRenal tubular epithelial cells are damaged in sepsis-associated acute kidney injury (S-AKI). In acute kidney injury (AKI) caused by ischemia, toxins and inflammatory factors, various forms of cell death are induced. In this study, we investigated the role and mechanism of disulfidptosis in the pathophysiological processes of S-AKI. NADPH was significantly downregulated in S-AKI mice, and closely involved in the occurrence of disulfidptosis. Interestingly, in the kidney tissues and cells of S-AKI mice, the disulfidptosis marker was significantly upregulated, actin cytoskeletal disulfide bond was formed, and cytoskeletal morphology contracted. Mechanistical studies showed that specific deletion of FDX1 in mouse kidney tissues and human renal tubular epithelial cells (HK-2) inhibited disulfidptosis and alleviated kidney injury in S-AKI. This was also demonstrated in HK-2 cell injury induced by the serum from children with sepsis. In addition, activating G6PD using G6PD agonist AG1 also significantly attenuated disulfidptosis and ameliorated renal injury. These findings suggest that FDX1 interacts with G6PD to induce NADPH depletion in renal tubular epithelial cells, thus activating disulfidptosis to exacerbate S-AKI. Blocking FDX1 through genetical or pharmacological methods may serve as a potential strategy against S-AKI.2026/09/30GSE347117GSM10046290GSM10046286GSM10046297GSM10046287GSM10046284GSM10046295GSM10046296GSM10046285GSM10046282GSM10046293GSM10046294GSM10046283GSM10046291GSM10046280GSM10046281GSM10046292GSM10046279GSM10046288GSM10046289GSM1004627824676347117Homo sapiens