{
  "abstract": "Background/objectives\n\nThe clinical utility of polymyxin B (PB), a critical last-line antibiotic for multidrug-resistant Gram-negative infections, is severely compromised by acute kidney injury (AKI). However, the lack of specific diagnostic biomarkers and the incomplete understanding of pathogenic mechanisms pose substantial challenges to clinical management of PB-associated AKI.Methods\n\nWe enrolled 83 patients receiving PB regimens (23 AKI, 60 non-AKI) and quantified the plasma concentrations of five PB components to identify the optimal therapeutic drug monitoring (TDM) metric for nephrotoxicity. A rat model of PB-induced AKI was established to map renal PB distribution via mass spectrometry imaging and screen targets for tubular accumulation virtually. Untargeted metabolomics was performed on clinical and rat samples to identify metabolic dysregulation, with key pathways validated by reverse transcription quantitative real-time PCR (RT-qPCR). Diagnostic models were constructed using the eXtreme Gradient Boosting (XGBoost) algorithm and evaluated using Area Under the Curve (AUC). Shapley Additive exPlanations (SHAP) analysis was applied to interpret the models, and decision curve analysis (DCA) was used to assess clinical utility.Results\n\nA novel PB-component model outperformed the conventional TDM index (AUC 0.703 vs. 0.561), and a 6-metabolite exploratory classifier achieved 0.95 accuracy and AUC 1.000 for PB-AKI discrimination on an independent test set. Mechanistically, high PB concentrations might saturate P-glycoprotein (P-gp), leading to PB accumulation in renal tubules and subsequent metabolic dysregulation, manifested as upregulation of fatty acid pathways and downregulation of the TCA cycle.Conclusions\n\nThese findings advance our understanding of metabolic dysregulation in PB-induced AKI and support the potential utility of responsive metabolic features in the clinical diagnosis of PB-induced AKI.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pharmacy, China-Japan Friendship Hospital, No. 2 Yinghua Road, Beijing 100029, China.",
    "Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.",
    "Institute of Chemicals Safety, Chinese Academy of Inspection and Quarantine, Beijing 100176, China.",
    "Comprehensive Test Center, Chinese Academy of Inspection and Quarantine, Beijing 100123, China.",
    "Department of Analysis and Testing, Shimadzu (China) Co., Ltd., Beijing 100020, China.",
    "Beijing Key Laboratory of Critical Bridging Technologies for Chronic Disease Drug Development, China-Japan Friendship Hospital, Beijing 100029, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Sirui Zhao"
    },
    {
      "affs": [
        0
      ],
      "name": "Wei Qin"
    },
    {
      "affs": [
        2
      ],
      "name": "Zirui Zhao"
    },
    {
      "affs": [
        0
      ],
      "name": "Ying Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Wenqian Chen"
    },
    {
      "affs": [
        3
      ],
      "name": "Yue Zhang"
    },
    {
      "affs": [
        3
      ],
      "name": "Juan Ren"
    },
    {
      "affs": [
        4
      ],
      "name": "Liang Sun"
    },
    {
      "affs": [
        4
      ],
      "name": "Lizhi Chen"
    },
    {
      "affs": [
        4
      ],
      "name": "Jingjing Shen"
    },
    {
      "affs": [
        0
      ],
      "name": "Pengmei Li"
    },
    {
      "affs": [
        0,
        5
      ],
      "name": "Xiaoxue Wang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9ht1jvcd3yrmm.bib",
  "cited_by": 0,
  "doi": "10.3390/antibiotics15100966",
  "fulltext_url": "https://europepmc.org/articles/PMC13700662",
  "id": "9ht1jvcd3yrmm",
  "issns": [
    "2079-6382"
  ],
  "landing_url": "https://europepmc.org/article/MED/42938707",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2727|Acute Kidney Injury Research"
    ]
  ],
  "openalex": "W7214948626",
  "pdf_url": "https://europepmc.org/articles/PMC13700662?pdf=render",
  "pmcid": "PMC13700662",
  "pmid": "42938707",
  "published": "2026-09-30",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/9ht1jvcd3yrmm.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:22:24Z",
      "native_id": "MED:42938707",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42938707"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2727|Acute Kidney Injury Research",
      "subfield": "general"
    }
  ],
  "title": "Diagnostic Biomarkers and Metabolic Mechanisms of Polymyxin B-Induced Acute Kidney Injury.",
  "title_text": "Diagnostic Biomarkers and Metabolic Mechanisms of Polymyxin B-Induced Acute Kidney Injury.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:22:24Z",
  "url": "https://research.draconitic.com/paper/9ht1jvcd3yrmm",
  "venue": "Antibiotics (Basel, Switzerland)",
  "versions": []
}