Evaluation of fetal and maternal vancomycin-induced kidney injury during pregnancy in a rat model

Medha D. Joshi, Gwendolyn M. Pais, Jack Chang, Khrystyna Hlukhenka, Sean N. Avedissian, Anil Gulati, Walter C. Prozialeck, Peter C. Lamar, Zhong Zhang, Marc H. Scheetz, Brooke Griffin

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Previous literature suggests that maternal vancomycin crosses the placental barrier to the fetus. Further, early animal studies indicated that kidney injury was not observed in the progeny. These studies were conducted prior to the availability of sensitive biomarkers for kidney injury. Therefore, a previous finding of no renal damage to the infant may be misleading. Vancomycin was administered intravenously to pregnant rats at a dose of 250 mg/kg of body weight/day (N = 6 per trimester) on three consecutive gestational days (GD) during trimesters 1, 2, and 3 (T1, T2, and T3, respectively) in three independent cohorts. The dams carried to term and delivered vaginally on GD 21. Kidneys were harvested from dams and pups and homogenized. Samples were prepared by protein precipitation and injected in a liquid chromatography tandem mass spectrometer, and vancomycin was quantified. The kidney tissue homogenate from dams and pups were analyzed for kidney injury molecule-1 (KIM-1). As trimesters progressed, the quantity of vancomycin increased linearly in the kidneys of both rat dams and pups (P < 0.0001 for T1 and T3, P < 0.0001 for T2 and T3, and P < 0.0001 for T3 and T3 control for both rat dams and pups). KIM-1 concentrations in pup kidneys were significantly higher when dams were administered vancomycin in trimesters 1 (P = 0.0001) and 2 (P = 0.0024) than in controls in trimester 3. Data demonstrate persistence of vancomycin in maternal and rat pup kidneys in all three trimesters of pregnancy with associated damage to the kidney, as indicated by expression of KIM-1.

Original languageEnglish (US)
Article numbere00761-19
JournalAntimicrobial Agents and Chemotherapy
Volume63
Issue number10
DOIs
StatePublished - 2019

Keywords

  • KIM-1
  • Maternal fetal exposure
  • Pregnancy
  • Rat model
  • Trimester
  • Vancomycin

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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