Dysregulation of SRSF3/<i>circSAMD4</i>/CIRBP Axis Promotes Iodinated Contrast-induced Acute Kidney Injury

Iodinated contrast agents are a common cause of contrast-induced acute kidney injury (CI-AKI), yet the underlying mechanisms remain unclear. We found that <i>circSAMD4</i> is markedly upregulated in renal tubular epithelial cells (RTECs) from iohexol-induced CI-AKI mice and patients diagnosed with acute tubular injury (ATI). Silencing <i>circSAMD4</i> alleviated kidney injury and tubular cell death in CI-AKI mice, whereas its overexpression promoted apoptosis in iohexol-treated RTECs. Mechanistically, <i>circSAMD4</i> binds to cold-inducible RNA-binding protein (CIRBP) and inhibits its nuclear import. Renal tubule-specific <i>Cirbp</i> deletion mitigated CI-AKI, while CIRBP overexpression abolished the protective effects of <i>circSAMD4</i> knockdown against iohexol-induced apoptosis. <i>CircSAMD4</i> upregulation in iohexol-treated RTECs was driven by serine/arginine-rich splicing factor 3 (SRSF3) downregulation. Similar molecular alterations in clinical samples correlated with kidney function decline. These findings identify the SRSF3/<i>circSAMD4</i>/CIRBP axis as a novel pathogenic mechanism in CI-AKI and highlight <i>circSAMD4</i> as a promising therapeutic target.