{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T14:28:27Z","timestamp":1788964107674,"version":"build-2803163510"},"reference-count":55,"publisher":"Wiley","license":[{"start":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T00:00:00Z","timestamp":1760572800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Physiology"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Sepsis\u2010associated acute kidney injury (SA\u2010AKI) is a common clinical syndrome in critically ill patients, and its high mortality rate is closely related to complex pathological mechanisms. Existing studies have shown that the pathophysiological process of SA\u2010AKI involves complex multi\u2010mechanism interactions, including an uncontrolled systemic inflammatory response, abnormal microcirculatory perfusion and disturbed cellular energy metabolism. Recent studies have shown that programmed necrosis (necroptosis) mediated by the receptor\u2010interacting protein kinase 1 (RIPK1)\/receptor\u2010interacting protein kinase 3 (RIPK3)\/mixed lineage kinase domain\u2010like protein (MLKL) signalling pathway plays a central role in SA\u2010AKI, driving the deterioration of renal function by directly inducing the death of renal tubular epithelial cells, exacerbating microcirculatory disorders and amplifying inflammation. Targeted inhibition of this pathway can reduce renal injury, but clinical translation is challenged by the lack of biomarkers, off\u2010target effects of drugs and the risk of infection. In this paper, we systematically review the molecular mechanisms of the RIPK1\/RIPK3\/MLKL pathway and its pathological contribution in SA\u2010AKI, summarize the efficacy and limitations of the existing inhibitors and explore the potential of combined therapeutic strategies. Future studies need to integrate single\u2010cell sequencing and clinical stratification through multidisciplinary collaboration to promote precision therapeutic breakthroughs.<\/jats:p>","DOI":"10.1113\/ep092229","type":"journal-article","created":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T05:44:49Z","timestamp":1760679889000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Role of RIPK1\/RIPK3\/MLKL signalling pathway in sepsis\u2010associated acute kidney injury"],"prefix":"10.1113","author":[{"given":"Huijun","family":"Yin","sequence":"first","affiliation":[{"name":"School of Anesthesiology Shandong Second Medical University  Weifang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyi","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Anesthesiology Shandong Second Medical University  Weifang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5491-8501","authenticated-orcid":false,"given":"Huirong","family":"Han","sequence":"additional","affiliation":[{"name":"School of Anesthesiology Shandong Second Medical University  Weifang China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,16]]},"reference":[{"issue":"1","key":"e_1_2_11_2_1","doi-asserted-by":"crossref","first-page":"127","DOI":"10.3390\/biomedicines10010127","article-title":"Interplay of oxidative stress and necrosis\u2010like cell death in cardiac ischemia\/reperfusion injury: A focus on necroptosis","volume":"10","author":"Adameova A.","year":"2022","journal-title":"Biomedicines"},{"issue":"1","key":"e_1_2_11_3_1","doi-asserted-by":"crossref","DOI":"10.1111\/cns.14397","article-title":"RIPK3 activation promotes DAXX\u2010dependent neuronal necroptosis after intracerebral hemorrhage in mice","volume":"30","author":"Bai Q.","year":"2023","journal-title":"CNS Neuroscience & Therapeutics"},{"issue":"5","key":"e_1_2_11_4_1","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1093\/bib\/bbv090","article-title":"Transcriptomic and metabolomic data integration","volume":"17","author":"Cavill R.","year":"2015","journal-title":"Briefings in Bioinformatics"},{"issue":"21","key":"e_1_2_11_5_1","doi-asserted-by":"crossref","DOI":"10.3390\/ijms232112714","article-title":"Necroptosis: A pathogenic negotiator in human diseases","volume":"23","author":"Chaouhan H. 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