Basic ResearchComplement activation is a crucial driver of acute kidney injury in rhabdomyolysis
Graphical abstract
Section snippets
Complement activation in kidneys of RIAKI patients
Ten biopsies of RIAKI patients were collected. The main features of the patients are summarized in Table 1. Kidney biopsies revealed a typical pattern of RIAKI, characterized by acute tubular necrosis (ATN) associated with tubular casts (Figure 1a). C3c staining was negative in the tubules in 8 of the 10 RIAKI patients, and in 2 control subjects: a patient with AKI (creatinine [Cr] = 420 μmol/l) caused by ATN without rhabdomyolysis and an allograft kidney biopsy from a patient 2 days after
Discussion
In addition to myoglobin casts and ATN, which are common histology features for rhabdomyolysis,24 complement deposits occurred in kidneys of mice and patients with RIAKI, independently from the rhabdomyolysis cause. Complement activation occurred intrarenally most likely by the lectin pathway via a C4-bypassing mechanism, and by the alternative pathway via heme. Intrarenal macrophages in RIAKI became particularly sensitive to complement, overexpressing C5aR and CD11b. C3−/− mice were protected
Methods
The complete Methods are provided in the Supplementary Methods.
Disclosure
LTR reports grants from CSL Behring, outside the submitted work. All the other authors declared no competing interests.
Acknowledgments
The cytometric and microscopy analyses were performed at the Centre d’Histologie, d’Imagerie et de Cytométrie (CHIC) and the Centre de Recherche des Cordeliers UMRS1138 (Paris, France). We are grateful to the CHIC team for the excellent technical assistance. CHIC is a member of the Université Pierre et Marie Curie Flow Cytometry Network. We are grateful for excellent technical assistance from the Centre d’Expérimentations Fonctionnelles team of the Centre de Recherche des Cordeliers and for
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