{
  "abstract": "Background: Evidence regarding the association between metoprolol use and acute kidney injury (AKI) remains limited, particularly because of time-varying exposure, cardiovascular confounding, and uncertain temporal ordering. We evaluated the association between recent metoprolol exposure and incident AKI using a longitudinal time-varying framework.\n\nMethods: This multicenter retrospective longitudinal cohort study included adult inpatients from three Chinese hospitals between January 2020 and December 2024. Eligible patients had an estimated glomerular filtration rate ≥60 mL min ⁻¹ ·1.73 m ⁻² at cohort entry and sufficient serial serum creatinine (Scr) and medication execution records. Metoprolol was modeled as a lag-1 time-varying exposure, relating use on hospital day t to AKI risk on day t +1. Incident AKI was identified using rolling KDIGO Scr criteria. Time-varying Cox regression adjusted for demographic characteristics, baseline renal function, major comorbidities, baseline severity-related factors, and lagged concomitant medication exposures. Sensitivity and complementary analyses evaluated the robustness of the findings.\n\nResults: Among 291,049 screened hospitalizations, 20,333 patients contributed 284,470 risk intervals, and 1,050 developed incident AKI. Lag-1 metoprolol exposure was associated with a higher AKI hazard in the unadjusted model (HR, 2.53; 95% CI, 2.13–3.00). The association was substantially attenuated after adjustment but remained statistically significant in the primary model (HR, 1.37; 95% CI, 1.05–1.79; P = 0.022). Prespecified follow-up-time analyses suggested that the association was concentrated during the first 72 h after cohort entry. Sensitivity analyses generally yielded estimates in the same direction, although the magnitude and statistical significance varied across analytical specifications; the association was attenuated to non-significance in the 2-day lag analysis (HR, 1.27; 95% CI, 0.96–1.68) and after additional adjustment for vasopressor use (HR, 1.29; 95% CI, 0.98–1.70). No consistent monotonic dose–response relationship was observed.\n\nConclusion: Recent metoprolol exposure was associated with a modestly higher hazard of incident AKI in the primary adjusted analysis. However, attenuation after adjustment, temporal heterogeneity, sensitivity to exposure timing and confounding control, and the absence of a consistent monotonic dose–response pattern suggest that residual confounding and clinical treatment context may contribute to the observed association. These findings should be interpreted as a hypothesis-generating short-term AKI safety signal rather than evidence of direct metoprolol nephrotoxicity or causality.",
  "abstract_shown": true,
  "affiliations": [
    "920th Hospital of the Joint Logistics Support Force of the Chinese People’s Liberation Army",
    "Department of Pharmacy, Guandu District People’s Hospital"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Zhengfu Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Hongkai Zha"
    },
    {
      "affs": [
        0
      ],
      "name": "Qingyun Gong"
    },
    {
      "affs": [
        1
      ],
      "name": "Meixian Wu"
    },
    {
      "affs": [
        1
      ],
      "name": "Yanyun She"
    },
    {
      "affs": [
        0
      ],
      "name": "Fan Xu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/cbq88att2sg39.bib",
  "cited_by": 0,
  "doi": "10.3389/fphar.2026.1899992",
  "fulltext_url": null,
  "id": "cbq88att2sg39",
  "issns": [
    "1663-9812"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1899992/full",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2727|Acute Kidney Injury Research"
    ]
  ],
  "openalex": "W7223178090",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-22",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/cbq88att2sg39.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:06Z",
      "native_id": "10.3389/fphar.2026.1899992",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1899992/full"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "issn:1663-9812",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "Time-varying metoprolol exposure and the risk of acute kidney injury: a multicenter retrospective cohort study",
  "title_text": "Time-varying metoprolol exposure and the risk of acute kidney injury: a multicenter retrospective cohort study",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:06Z",
  "url": "https://research.draconitic.com/paper/cbq88att2sg39",
  "venue": "Frontiers in Pharmacology",
  "versions": []
}