Vancomycin-Associated Cast Nephropathy

作者：Yosu Luque, Kévin Louis, Chantal Jouanneau, Sandrine Placier, Emmanuel Estève, Dominique Bazin, Éric Rondeau, Emmanuel Letavernier, Alice Wolfromm, Clément Gosset, Anna Boueilh, Maren Burbach, Perrine Frère, Marie‐Christine Verpont, Sophie Vandermeersch, Dominique Langui, Michel Daudon, Vincent Frochot, Laurent Mesnard · 发表于：Journal of the American Society of Nephrology · 年份：2017 · DOI：10.1681/asn.2016080867 · 被引用次数：153 · 研究领域：Antimicrobial Resistance in Staphylococcus、Clostridium difficile and Clostridium perfringens research、Bacterial Identification and Susceptibility Testing

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.