Kidney biopsy findings in vancomycin-induced acute kidney injury: a pooled analysis

Abstract

Acute kidney injury represents a major adverse effect of vancomycin administration. The aim of the present study is to accumulate all biopsy-proven cases of vancomycin nephrotoxicity and assess the association of histopathological features with renal prognosis. Medline, Scopus, CENTRAL, Web of Science, and Clinicaltrials.gov were systematically searched from inception to 29 September 2020. All case reports/series providing individual data of patients with biopsy-proven vancomycin nephrotoxicity were held eligible. A time-to-event analysis was performed evaluating the effects of histological diagnosis on renal recovery. Overall, 18 studies were included, comprising 21 patients. Acute tubulointerstitial nephritis was the predominant pattern in 9 patients and was associated with a significantly higher risk of permanent renal dysfunction (HR: 5.08, 95% CI: [1.05-24.50)] compared to acute tubular necrosis. Tubulitis and eosinophilic infiltration were the most common histopathological findings, while interstitial fibrosis was linked to significantly worse renal prognosis (HR: 5.55, 95% CI: 1.13-27.27). Immunofluorescence and electron microscopy features were non-specific. Obstruction by tubular casts composed of vancomycin aggregates and uromodulin has been identified as a new mechanism of nephrotoxicity. Acute tubular necrosis and tubulointerstitial nephritis represent the main histological patterns of vancomycin-induced acute kidney injury. The presence of fibrosis in the context of interstitial inflammation may be linked to lower recovery rates and worse long-term renal outcomes. A novel cast nephropathy obstructive mechanism has been suggested, necessitating further confirmation. Large-scale studies should define the exact indications of kidney biopsy in cases with suspected vancomycin nephrotoxicity.