title: Vancomycin-Associated Cast Nephropathy.
abstract: 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 differentin vivoimaging 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.
authors.affiliation: Urgences Néphrologiques et Transplantation rénale, Hôpital Tenon, Assistance Publique - Hôpitaux de Paris, Paris, France.|Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche_S1155, Rare and Common Kidney Diseases, Matrix Remodeling and Tissue Repair, Paris, France.|Sorbonne Universités, Université Pierre et Marie Curie Univ Paris 6, Paris, France.
authors.forename: Yosu
authors.initials: Y
authors.lastname: Luque
authors.affiliation: Urgences Néphrologiques et Transplantation rénale, Hôpital Tenon, Assistance Publique - Hôpitaux de Paris, Paris, France.
authors.forename: Kevin
authors.initials: K
authors.lastname: Louis
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche_S1155, Rare and Common Kidney Diseases, Matrix Remodeling and Tissue Repair, Paris, France.
authors.forename: Chantal
authors.initials: C
authors.lastname: Jouanneau
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche_S1155, Rare and Common Kidney Diseases, Matrix Remodeling and Tissue Repair, Paris, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Placier
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche_S1155, Rare and Common Kidney Diseases, Matrix Remodeling and Tissue Repair, Paris, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Esteve
authors.affiliation: Sorbonne Universités, Université Pierre et Marie Curie Univ Paris 6, Paris, France.|Laboratoire de chimie de la matière condensée de Paris, Collège de France, Centre régional de la Recherche Scientifique Unité Mixte de Recherche_7574, Laboratoire de physique des solides, université Paris XI, Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Bazin
authors.affiliation: Urgences Néphrologiques et Transplantation rénale, Hôpital Tenon, Assistance Publique - Hôpitaux de Paris, Paris, France.|Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche_S1155, Rare and Common Kidney Diseases, Matrix Remodeling and Tissue Repair, Paris, France.|Sorbonne Universités, Université Pierre et Marie Curie Univ Paris 6, Paris, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Rondeau
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche_S1155, Rare and Common Kidney Diseases, Matrix Remodeling and Tissue Repair, Paris, France.|Sorbonne Universités, Université Pierre et Marie Curie Univ Paris 6, Paris, France.|Explorations fonctionnelles multidisciplinaires, Hôpital Tenon, Assistance Publique - Hôpitaux de Paris, Paris, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Letavernier
authors.affiliation: Hématologie Clinique Adulte, Hôpital Necker- Enfants malades, Assistance Publique - Hôpitaux de Paris, Paris, France.
authors.forename: Alice
authors.initials: A
authors.lastname: Wolfromm
authors.affiliation: Anatomie pathologique, Hôpital Saint-Louis, Assistance Publique - Hôpitaux de Paris, Paris, France.
authors.forename: Clément
authors.initials: C
authors.lastname: Gosset
authors.affiliation: Néphrologie-Transplantation, Hôpital Saint-Louis, Assistance Publique - Hôpitaux de Paris, Paris, France.
authors.forename: Anna
authors.initials: A
authors.lastname: Boueilh
authors.affiliation: Néphrologie-Transplantation, Hôpital Saint-Louis, Assistance Publique - Hôpitaux de Paris, Paris, France.
authors.forename: Maren
authors.initials: M
authors.lastname: Burbach
authors.affiliation: Imaging and Cytometry Facility of Tenon, Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche_S1155, Rare and Common Kidney Diseases, Matrix Remodelling and Tissue Repair, Sorbonne Universités, Université Pierre et Marie Curie Univ Paris 6, Paris, France; and.
authors.forename: Perrine
authors.initials: P
authors.lastname: Frère
authors.affiliation: Imaging and Cytometry Facility of Tenon, Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche_S1155, Rare and Common Kidney Diseases, Matrix Remodelling and Tissue Repair, Sorbonne Universités, Université Pierre et Marie Curie Univ Paris 6, Paris, France; and.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Verpont
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche_S1155, Rare and Common Kidney Diseases, Matrix Remodeling and Tissue Repair, Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Vandermeersch
authors.affiliation: Plateforme d'imagerie cellulaire Pitié-Salpêtrière, Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche_S1127/Centre régional de la Recherche Scientifique Unité Mixte de Recherche_7225/Université Pierre et Marie Curie, Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Langui
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche_S1155, Rare and Common Kidney Diseases, Matrix Remodeling and Tissue Repair, Paris, France.|Sorbonne Universités, Université Pierre et Marie Curie Univ Paris 6, Paris, France.|Explorations fonctionnelles multidisciplinaires, Hôpital Tenon, Assistance Publique - Hôpitaux de Paris, Paris, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Daudon
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche_S1155, Rare and Common Kidney Diseases, Matrix Remodeling and Tissue Repair, Paris, France.|Explorations fonctionnelles multidisciplinaires, Hôpital Tenon, Assistance Publique - Hôpitaux de Paris, Paris, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Frochot
authors.affiliation: Urgences Néphrologiques et Transplantation rénale, Hôpital Tenon, Assistance Publique - Hôpitaux de Paris, Paris, France; laurent.mesnard@aphp.fr.|Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche_S1155, Rare and Common Kidney Diseases, Matrix Remodeling and Tissue Repair, Paris, France.|Sorbonne Universités, Université Pierre et Marie Curie Univ Paris 6, Paris, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Mesnard
mesh_terms: D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology; D008875:Middle Aged; D058949:Uromodulin / Q000378:metabolism; D014640:Vancomycin / Q000009:adverse effects* / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D058949:Uromodulin; D014640:Vancomycin
keywords: acute renal failure; acute tubular necrosis; tubular cast; tubular epithelium; vancomycin