The temporal gene expression landscape of rhabdomyolysis-induced acute kidney injury reveals the timing of complement activation
Rhabdomyolysis-induced acute kidney injury (RIAKI) involves complement activation, but its role as a therapeutic target remains unclear. 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.
Authors
- T. Woodruff
- Marie Frimat (ORCID: https://orcid.org/0000-0002-7461-8298)
- S. Gaudry
- Idris Boudhabhay (ORCID: https://orcid.org/0000-0002-8045-1658)
- Victoria Poillerat (ORCID: https://orcid.org/0009-0000-2542-7199)
- Anne Grünenwald
- Gilles Crambert (ORCID: https://orcid.org/0000-0001-7065-9124)
- Mohamad Khairul Amir Zaidan
- H. Nielly (ORCID: https://orcid.org/0000-0002-8042-5716)
- Margot Revel
- Julie Oniszczuk
- Laurent Gilardin (ORCID: https://orcid.org/0000-0001-9212-0859)
- Amine Majdi (ORCID: https://orcid.org/0009-0006-4692-1093)
- Khalil Chaïbi (ORCID: https://orcid.org/0000-0001-9106-586X)
- M. Aletti
- Julien Guihaire (ORCID: https://orcid.org/0000-0001-7414-3176)
- Elodie Voilin
- Lubka Roumenina
- Viviane Gnemmi
Institutions
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- The University of Queensland (AU)
- Université Paris Cité (FR)
- Université de Lille (FR)
- Université Paris-Saclay (FR)
- Centre Hospitalier Universitaire de Lille (FR)
- Sorbonne Université (FR)
- Université Sorbonne Paris Nord (FR)
- Sorbonne Paris Cité (FR)
- Centre de Recherche des Cordeliers (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- Fédération Hospitalo-Universitaire, Paris Center for Microbiome Medicine (FR)
- Centre Hospitalier Intercommunal de Poissy (FR)
- Metabolism and Renal Physiology (FR)
- Hôpital Avicenne (FR)
- Hôpital d'Instruction des Armées Bégin (FR)
- Hôpital Paris Saint-Joseph (FR)
- Hôpital d'instruction des Armées Percy (FR)
- Hôpital Jean-Verdier (FR)
- Hôpital Foch (FR)
- Bicêtre Hospital (FR)
- Hôpital Tenon (FR)
- CANTHER - Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers (FR)
- Maladies rénales fréquentes et rares : des mécanismes moléculaires à la médecine personnalisée
Publication Details
- Journal
- Communications Biology
- Published
- 2025-12-31
- DOI
- https://doi.org/10.1038/s42003-025-09449-y
- Primary Topic
- Complement system in diseases
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- European Commission
- Agence Nationale de la Recherche
- Institut National de la Santé et de la Recherche Médicale
- Fondation pour la Recherche Médicale
- Sorbonne Université
- Université de Paris