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We analyze urine and kidney biopsies from RIAKI patients and use a glycerol-induced mouse model to investigate complement activation and its contribution to RIAKI. Here we show that complement fragments Ba, Bb, C5a, and sC5b-9 are elevated in the urine of patients with RIAKI, and C3 staining is detected in injured tubules, often surrounded by C5aR1-expressing myeloid cells. However, pharmacologic C5 or C5aR1 inhibition fail to prevent RIAKI in mice. A kinetic analysis reveal that complement activation occurs later in the disease course, following early tubular injury and immune cell infiltration. Initial cytoprotective responses are rapidly overwhelmed, leading to tubular damage and chemokine-driven C5aR1-expressing myeloid cells recruitment. These findings suggest that complement cascade is not an initiating factor in RIAKI and underscore the multifactorial nature of this disease.<\/jats:p>","DOI":"10.1038\/s42003-025-09449-y","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T03:15:41Z","timestamp":1767150941000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The temporal gene expression landscape of rhabdomyolysis-induced acute kidney injury reveals the timing of complement activation"],"prefix":"10.1038","volume":"9","author":[{"given":"Anne","family":"Grunenwald","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8045-1658","authenticated-orcid":false,"given":"Idris","family":"Boudhabhay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margot","family":"Revel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Poillerat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elodie","family":"Voilin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4692-1093","authenticated-orcid":false,"given":"Amine","family":"Majdi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khalil","family":"Chaibi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephane","family":"Gaudry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1382-911X","authenticated-orcid":false,"given":"Trent M.","family":"Woodruff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilles","family":"Crambert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Guihaire","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamad","family":"Zaidan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Oniszczuk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Frimat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viviane","family":"Gnemmi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Aletti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8042-5716","authenticated-orcid":false,"given":"Hubert","family":"Nielly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Gilardin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9940-0324","authenticated-orcid":false,"given":"Lubka T.","family":"Roumenina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,31]]},"reference":[{"key":"9449_CR1","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1038\/s41581-023-00758-1","volume":"20","author":"A Zarbock","year":"2024","unstructured":"Zarbock, A. et al. 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