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The onset and the injury of acute kidney injury caused by ischemia or drugs also have a circadian rhythmicity. Contrast media are widely used in clinical diagnosis and treatment; however, whether contrast\u2010induced kidney injury exhibits a time\u2010of\u2010day dependence is unknown. We retrospectively analyzed 33 patients who underwent percutaneous coronary angiography and found that contrast induced the increase of serum neutrophil gelatinase\u2010associated lipocalin (NGAL) was more obvious in the group who underwent operation during 6:00\u2009~\u200913:00 than the group who underwent operation between 13:00\u2009~\u200920:00. In addition, C57BL\/6J mice were injected with iohexol at different times. The kidney injury of mice injected with iohexol at ZT12 was more severe than that at ZT0, which was manifested in the increase of urinary KIM1 and NGAL, enhanced renal tubular lipid peroxidation, and increased tubular ferroptosis. Inhibition of ferroptosis could alleviate kidney injury induced by iohexol at ZT12. Mechanistically, we found that nuclear factor erythrocyte 2\u2010associated factor 2 (NRF2) expression has a 24\u2010h circadian rhythm and is directly regulated by CLOCK. Administration of 4\u2010Octyl itaconate at ZT12 to increase NRF2 expression could attenuate iohexol\u2010induced tubular ferroptosis. These findings provide a new insight into the pathology of contrast medium\u2010induced kidney injury, in which oscillatory NRF2 expression regulated by CLOCK contributes to the susceptibility of contrast\u2010induced kidney injury in a time\u2010of\u2010day\u2013specific fashion.<\/jats:p>","DOI":"10.1002\/iub.70022","type":"journal-article","created":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T11:54:30Z","timestamp":1747742070000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Contrast\u2010Induced Acute Kidney Injury is Modulated by Circadian <scp>CLOCK<\/scp>\/<scp>NRF2<\/scp> Pathway"],"prefix":"10.1002","volume":"77","author":[{"given":"Shuqing","family":"Yang","sequence":"first","affiliation":[{"name":"Center for Kidney Disease The Second Affiliated Hospital, Nanjing Medical University  Nanjing Jiangsu China"},{"name":"Nantong First People's Hospital The Second Affiliated Hospital of Nantong 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