PMID- 31332061 OWN - NLM STAT- MEDLINE DCOM- 20200707 LR - 20200707 IS - 1098-6596 (Electronic) IS - 0066-4804 (Print) IS - 0066-4804 (Linking) VI - 63 IP - 10 DP - 2019 Oct TI - Evaluation of Fetal and Maternal Vancomycin-Induced Kidney Injury during Pregnancy in a Rat Model. LID - 10.1128/AAC.00761-19 [doi] LID - e00761-19 AB - 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. CI - Copyright (c) 2019 American Society for Microbiology. FAU - Joshi, Medha D AU - Joshi MD AUID- ORCID: 0000-0002-0280-0349 AD - Department of Pharmaceutical Sciences, Chicago College of Pharmacy, Midwestern University, Downers Grove, Illinois, USA mjoshi@midwestern.edu. AD - Department of Biomedical Sciences, College of Graduate Studies, Midwestern University, Downers Grove, Illinois, USA. AD - Pharmacometrics Center of Excellence, Midwestern University, Downers Grove, Illinois, USA. FAU - Pais, Gwendolyn M AU - Pais GM AD - Department of Pharmacy Practice, Chicago College of Pharmacy, Midwestern University, Downers Grove, Illinois, USA. AD - Pharmacometrics Center of Excellence, Midwestern University, Downers Grove, Illinois, USA. FAU - Chang, Jack AU - Chang J AD - Department of Pharmaceutical Sciences, Chicago College of Pharmacy, Midwestern University, Downers Grove, Illinois, USA. FAU - Hlukhenka, Khrystyna AU - Hlukhenka K AD - Department of Pharmaceutical Sciences, Chicago College of Pharmacy, Midwestern University, Downers Grove, Illinois, USA. FAU - Avedissian, Sean N AU - Avedissian SN AUID- ORCID: 0000-0002-0935-6455 AD - Department of Pharmacy Practice, Chicago College of Pharmacy, Midwestern University, Downers Grove, Illinois, USA. AD - Pharmacometrics Center of Excellence, Midwestern University, Downers Grove, Illinois, USA. FAU - Gulati, Anil AU - Gulati A AUID- ORCID: 0000-0002-7420-4554 AD - Department of Pharmaceutical Sciences, Chicago College of Pharmacy, Midwestern University, Downers Grove, Illinois, USA. AD - Department of Biomedical Sciences, College of Graduate Studies, Midwestern University, Downers Grove, Illinois, USA. AD - Pharmacometrics Center of Excellence, Midwestern University, Downers Grove, Illinois, USA. FAU - Prozialeck, Walter C AU - Prozialeck WC AD - Department of Pharmacology, College of Graduate Studies, Midwestern University, Downers Grove, Illinois, USA. FAU - Lamar, Peter C AU - Lamar PC AD - Department of Pharmacology, College of Graduate Studies, Midwestern University, Downers Grove, Illinois, USA. FAU - Zhang, Zhong AU - Zhang Z AD - Department of Pharmaceutical Sciences, Chicago College of Pharmacy, Midwestern University, Downers Grove, Illinois, USA. FAU - Scheetz, Marc H AU - Scheetz MH AUID- ORCID: 0000-0002-1091-6130 AD - Department of Pharmacy Practice, Chicago College of Pharmacy, Midwestern University, Downers Grove, Illinois, USA. AD - Department of Pharmacology, College of Graduate Studies, Midwestern University, Downers Grove, Illinois, USA. AD - Pharmacometrics Center of Excellence, Midwestern University, Downers Grove, Illinois, USA. FAU - Griffin, Brooke AU - Griffin B AD - Department of Pharmacy Practice, Chicago College of Pharmacy, Midwestern University, Downers Grove, Illinois, USA. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190923 PL - United States TA - Antimicrob Agents Chemother JT - Antimicrobial agents and chemotherapy JID - 0315061 RN - 6Q205EH1VU (Vancomycin) SB - IM MH - Animals MH - Animals, Newborn MH - Body Weight/drug effects MH - Female MH - Fetus MH - Kidney/*drug effects MH - Kidney Diseases/*chemically induced MH - Placenta/drug effects MH - Pregnancy MH - Prenatal Care MH - Rats MH - Rats, Sprague-Dawley MH - Vancomycin/*adverse effects PMC - PMC6761542 OTO - NOTNLM OT - KIM-1 OT - maternal fetal exposure OT - pregnancy OT - rat model OT - trimester OT - vancomycin EDAT- 2019/07/25 06:00 MHDA- 2020/07/08 06:00 PMCR- 2020/03/23 CRDT- 2019/07/24 06:00 PHST- 2019/04/08 00:00 [received] PHST- 2019/07/11 00:00 [accepted] PHST- 2019/07/25 06:00 [pubmed] PHST- 2020/07/08 06:00 [medline] PHST- 2019/07/24 06:00 [entrez] PHST- 2020/03/23 00:00 [pmc-release] AID - AAC.00761-19 [pii] AID - 00761-19 [pii] AID - 10.1128/AAC.00761-19 [doi] PST - epublish SO - Antimicrob Agents Chemother. 2019 Sep 23;63(10):e00761-19. doi: 10.1128/AAC.00761-19. Print 2019 Oct.