{
  "abstract": "Although acute kidney injury (AKI) has been implicated as a potential adverse effect of statin therapy, experimental evidence supporting this association remains limited. Here, we investigated whether elevated levels of 25-hydroxycholesterol (25-HC), an oxysterol produced by activated macrophages and monocytes, increase susceptibility to statin-induced AKI. We found that atorvastatin and fluvastatin induced cell death in proximal tubular cells when combined with 25-HC. Consistently, administration of low-dose lipopolysaccharide triggered AKI in statin-treated mice. Mechanistically, impaired protein prenylation disrupted the autophagosome-lysosome pathway in proximal tubular cells. AKI was attenuated by mevalonate supplementation, which restored protein prenylation, and by macrophage/monocyte depletion, which reduced the cellular sources of 25-HC. Furthermore, combined exposure to fluvastatin and 25-HC increased kidney injury molecule-1 (KIM-1) expression in human induced pluripotent stem cell-derived kidney organoids. Together, these findings suggest that elevated macrophage-derived 25-HC under conditions of infection, inflammation, or major surgery may increase susceptibility to statin-induced AKI. Our study identifies a previously unrecognized interaction between statins and 25-HC and suggests potential strategies to mitigate kidney injury while preserving the therapeutic benefits of statins.",
  "abstract_shown": true,
  "affiliations": [
    "Yonsei University College of Medicine"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "C. H. Kim"
    },
    {
      "name": "H. J. Wang"
    },
    {
      "name": "Y. Cho"
    },
    {
      "name": "J. H. Lee"
    },
    {
      "name": "J. Yoon"
    },
    {
      "affs": [
        0
      ],
      "name": "H.-Y. Kim"
    },
    {
      "name": "Y. Jung"
    },
    {
      "name": "H. Lee"
    },
    {
      "name": "H. Y. Choi"
    },
    {
      "name": "J.-Y. Lee"
    },
    {
      "name": "H. Y. Gee"
    },
    {
      "affs": [
        0
      ],
      "name": "B. s. Kim"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9cpb0f11msrqn.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.16.759612",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.16.759612v1.full",
  "id": "9cpb0f11msrqn",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.16.759612v1",
  "language": null,
  "licence": "CC-BY-ND",
  "licence_label": "CC BY-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "pharmacology and toxicology"
    ],
    [
      "openalex",
      "2727|Acute Kidney Injury Research"
    ]
  ],
  "openalex": "W7223248494",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.16.759612v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-16",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/9cpb0f11msrqn.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:29:12Z",
      "native_id": "10.64898/2026.10.16.759612",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.16.759612v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:pharmacology and toxicology",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "Macrophage-Derived 25-Hydroxycholesterol Drives Statin-Associated Acute Kidney Injury",
  "title_text": "Macrophage-Derived 25-Hydroxycholesterol Drives Statin-Associated Acute Kidney Injury",
  "type": "preprint",
  "updated_at": "2026-10-30T12:29:12Z",
  "url": "https://research.draconitic.com/paper/9cpb0f11msrqn",
  "venue": "bioRxiv",
  "versions": []
}