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Article Dans Une Revue Journal of the American Society of Nephrology Année : 2017

Vancomycin-Associated Cast Nephropathy

Kevin Louis
  • Fonction : Auteur

Résumé

Vancomycin is a widely prescribed antibiotic, but the exact nature of vancomycin-associated nephrotoxicity is unclear, in particular when considering the frequent coadministration of aminoglycosides. We describe here the initial case of a 56-year-old woman with normal renal function developing unexplained ARF without hypovolemia after administration of vancomycin without coadministration of aminoglycosides. Studying the patient’s renal biopsy specimen, we ascertained that obstructive tubular casts composed of noncrystal nanospheric vancomycin aggregates entangled with uromodulin explained the vancomycin-associated ARF. We developed in parallel a new immunohistologic staining technique to detect vancomycin in renal tissue and confirmed retrospectively that deleterious vancomycin-associated casts existed in eight additional patients with acute tubular necrosis in the absence of hypovolemia. Concomitant high vancomycin trough plasma levels had been observed in each patient. We also reproduced experimentally the toxic and obstructive nature of vancomycin-associated cast nephropathy in mice, which we detected using different in vivo imaging techniques. In conclusion, the interaction of uromodulin with nanospheric vancomycin aggregates represents a new mode of tubular cast formation, revealing the hitherto unsuspected mechanism of vancomycin-associated renal injury.
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Dates et versions

hal-01437592 , version 1 (22-06-2018)

Identifiants

Citer

Yosu Luque, Kevin Louis, Chantal Jouanneau, Sandrine Placier, Emmanuel Esteve, et al.. Vancomycin-Associated Cast Nephropathy. Journal of the American Society of Nephrology, 2017, 28 (6), pp.ASN.2016080867. ⟨10.1681/ASN.2016080867⟩. ⟨hal-01437592⟩
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