{
  "abstract": "The NLRP3 inflammasome has emerged as a potential molecular link between cellular stress, sterile inflammation, and progressive kidney damage. This review critically examines canonical, non-canonical, and mitochondrial mechanisms of NLRP3 regulation across the acute kidney injury (AKI)–acute kidney disease (AKD)–chronic kidney disease (CKD) continuum, integrating their relationships with pyroptosis, maladaptive repair, fibrosis, and epigenetic regulation. Particular attention is given to endocrine–metabolic signals that may shape renal inflammasome activity. Hyperglycemia, advanced glycation end products, mitochondrial reactive oxygen species, TXNIP signaling, lipotoxicity, impaired tubular fatty-acid oxidation, podocyte insulin resistance, obesity-related adipokine imbalance, and aldosterone-mineralocorticoid receptor activation may converge on NLRP3. Conversely, inflammasome-dependent cytokine release and pyroptosis may amplify insulin resistance, metabolic dysfunction, and cardiorenal injury, establishing a bidirectional endocrine-renal inflammatory loop. Importantly, increased NLRP3 mRNA or protein abundance is distinguished from functional inflammasome activation, which is more strongly supported by downstream evidence such as ASC recruitment/oligomerization, caspase-1 activation, mature IL-1β/IL-18 production, GSDMD cleavage, or pyroptotic cell death. A central issue is whether NLRP3 is a causal driver of kidney disease or a marker of ongoing tissue injury. Although genetic and pharmacological studies support a pathogenic role in experimental models, clinical evidence remains largely associative and disease-dependent. NLRP3-related signals should therefore be regarded as candidate, rather than validated, biomarkers. SGLT2 inhibitors, GLP-1 receptor agonists and finerenone may indirectly attenuate NLRP3 signaling, but mechanistic mediation of their clinical benefits remains unproven. Defining cell-specific activation and clinical target engagement will be essential to establish NLRP3 as a biomarker and therapeutic target.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Biology, Ecology and Earth Sciences, University of Calabria, 87036 Rende, Italy",
    "Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy",
    "Department of Health Sciences, Magna Graecia University, 88100 Catanzaro, Italy",
    "Department of Surgery, Division of Urology, Annunziata Hospital, 87100 Cosenza, Italy",
    "Endocrine and Metabolic diseases Unit, Annunziata Hospital, 87100 Cosenza, Italy"
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Daniele La Russa",
      "orcid": "0000-0003-1887-2854"
    },
    {
      "affs": [
        1
      ],
      "name": "Sabrina Bossio",
      "orcid": "0009-0006-1831-0324"
    },
    {
      "affs": [
        2
      ],
      "name": "Antonella La Russa",
      "orcid": "0000-0002-9173-9657"
    },
    {
      "affs": [
        1,
        3
      ],
      "name": "Michele Di Dio"
    },
    {
      "affs": [
        0
      ],
      "name": "Daniela Pellegrino",
      "orcid": "0000-0002-9815-5195"
    },
    {
      "affs": [
        1,
        4
      ],
      "name": "Anna Perri",
      "orcid": "0000-0002-2852-0919"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/74p5g392x6jh8.bib",
  "cited_by": 0,
  "doi": "10.3390/ijms27209176",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13705395/?tool=EBI",
  "id": "74p5g392x6jh8",
  "issns": [
    "1422-0067"
  ],
  "landing_url": "https://www.mdpi.com/1422-0067/27/20/9176",
  "language": "eng",
  "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",
      "1312|Inflammasome and immune disorders"
    ]
  ],
  "openalex": "W7222604591",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13705395/pdf/?tool=EBI",
  "pmcid": "PMC13705395",
  "pmid": null,
  "published": "2026-10-01",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/74p5g392x6jh8.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:57Z",
      "native_id": "10.3390/ijms27209176",
      "source": "crossref",
      "url": "https://www.mdpi.com/1422-0067/27/20/9176"
    },
    {
      "first_seen": "2026-10-30T12:21:44Z",
      "native_id": "PMC:PMC13705395",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13705395"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Inflammasome and immune disorders",
      "subfield": "molecular-biology"
    }
  ],
  "title": "The NLRP3 Inflammasome Across the AKI–AKD–CKD Continuum: Mitochondrial, Epigenetic and Endocrine–Metabolic Regulation",
  "title_text": "The NLRP3 Inflammasome Across the AKI–AKD–CKD Continuum: Mitochondrial, Epigenetic and Endocrine–Metabolic Regulation",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:21:44Z",
  "url": "https://research.draconitic.com/paper/74p5g392x6jh8",
  "venue": "International Journal of Molecular Sciences",
  "versions": []
}