{"doi":"10.1101/2023.03.09.532007","title":"Iohexol-measured glomerular filtration rate and urinary biomarker changes between vancomycin and vancomycin plus piperacillin-tazobactam in a translational rat model","abstract":"Recent clinical studies have reported additive nephrotoxicity with the combination of vancomycin and piperacillin-tazobactam. However, preclinical models have failed to replicate this finding. This study assessed differences in iohexol-measured glomerular filtration rate (GFR) and urinary injury biomarkers among rats receiving this antibiotic combination. Male Sprague-Dawley rats received either intravenous vancomycin, intraperitoneal piperacillin-tazobactam, or both for 96 hours. Iohexol-measured GFR was used to quantify real-time kidney function changes. Kidney injury was evaluated via the urinary biomarkers: kidney injury molecule-1 (KIM-1), clusterin, and osteopontin. Compared to the control, rats that received vancomycin had numerically lower GFR after drug dosing on day 3. Rats in this group also had elevations in urinary KIM-1 on experimental days 2 and 4. Increasing urinary KIM-1 was found to correlate with decreasing GFR on experimental days 1 and 3. Rats that received vancomycin+piperacillin-tazobactam did not exhibit worse kidney function or injury biomarkers compared to vancomycin alone. The combination of vancomycin+piperacillin-tazobactam does not cause additive nephrotoxicity in a translational rat model. Future clinical studies investigating this antibiotic combination should employ more sensitive biomarkers of kidney function and injury, similar to those utilized in this study.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":398704,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9599,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":565595,"name":"Gwendolyn Pais","orcid":null,"position":1,"is_corresponding":false},{"id":832480,"name":"Sylwia Marianski","orcid":null,"position":2,"is_corresponding":false},{"id":832479,"name":"Kimberly Valdez","orcid":null,"position":3,"is_corresponding":false},{"id":1148737,"name":"Emily Lesnicki","orcid":null,"position":4,"is_corresponding":false},{"id":307082,"name":"Erin F. Barreto","orcid":"0000-0002-0996-1487","position":5,"is_corresponding":false},{"id":339322,"name":"Nathaniel J. Rhodes","orcid":"0000-0002-0018-5434","position":6,"is_corresponding":false},{"id":490062,"name":"Paul R. Yarnold","orcid":"0000-0002-1648-739X","position":7,"is_corresponding":false},{"id":339323,"name":"Marc H. Scheetz","orcid":"0000-0002-1091-6130","position":8,"is_corresponding":false},{"id":536554,"name":"Jack Chang","orcid":"0000-0002-5645-0014","position":0,"is_corresponding":true}],"reference_count":37,"raw_metadata":null,"created_at":"2026-07-19T01:19:47.744358Z","pmid":"36945555","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}