{
  "abstract": "Diabetic kidney disease (DKD) remains the leading cause of end-stage renal disease worldwide, yet current therapeutic approaches fail to fully halt its progression. Emerging evidence identifies lactate not merely as a glycolytic byproduct, but as a critical signaling molecule that drives DKD pathogenesis via lysine lactylation. This review delineates the mechanistic cascade from upstream metabolic dysregulation to epigenetic reprogramming and renal injury. We first describe how the hyperglycemic and hypoxic microenvironment stabilizes hypoxia-inducible factor-1α (HIF-1α), initiating a positive feedback loop that amplifies glycolytic flux and lactate accumulation. Then, we discuss the dynamic regulation of lactylation by “writer” enzymes and “eraser” enzymes. Furthermore, we analyze how lactate-induced lactylation may contribute to metabolic and immune-inflammatory remodeling across key renal cells: promoting podocyte epithelial-mesenchymal transition (EMT) and autophagy suppression; driving tubular fibrosis and ferroptosis via specific lactylation axes; and activating glomerular endothelial NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasomes. Beyond lactylation, we address other lactate-mediated mechanisms, including GPR81 signaling and intracellular acidification. Finally, we evaluate therapeutic strategies targeting this pathway-such as SGLT2 inhibitors and traditional Chinese medicine-and discuss the challenges in clinical translation. By integrating the latest mechanistic advances, this review discusses lactate-induced lactylation as a potential hub that may connect metabolic, epigenetic, and immune injury, while acknowledging that renal inflammation in DKD arises from diverse upstream pathways, providing a roadmap for the development of next-generation biomarkers and targeted therapies.",
  "abstract_shown": true,
  "affiliations": [
    "Beijing Luhe Hospital, Capital Medical University",
    "Center for Endocrine Metabolism and Immune Diseases, Beijing Luhe Hospital, Capital Medical University",
    "Beijing Key Laboratory of Artificial Intelligence and Cell-based Medical Engineering for Interdisciplinary Innovation and Clinical Translation",
    "Laboratory for Clinical Medicine, Capital Medical University"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Shihao He"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Longyan Yang"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Ruili Yin"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fgs2xp123sntj.bib",
  "cited_by": 0,
  "doi": "10.3389/fphar.2026.1950569",
  "fulltext_url": null,
  "id": "fgs2xp123sntj",
  "issns": [
    "1663-9812"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1950569/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|Chronic Kidney Disease and Diabetes"
    ]
  ],
  "openalex": "W7223184873",
  "pdf_url": "https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2026.1950569/pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-22",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/fgs2xp123sntj.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:06Z",
      "native_id": "10.3389/fphar.2026.1950569",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1950569/full"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "issn:1663-9812",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "Mechanistic insights into lactate-driven pathogenesis in diabetic kidney disease",
  "title_text": "Mechanistic insights into lactate-driven pathogenesis in diabetic kidney disease",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:06Z",
  "url": "https://research.draconitic.com/paper/fgs2xp123sntj",
  "venue": "Frontiers in Pharmacology",
  "versions": []
}