{
  "abstract": "Introduction: Fibrogenesis contributes to disease progression in patients with autosomal dominant polycystic kidney disease (ADPKD). In this exploratory study, we evaluated the association of protease-generated circulating and urinary collagen fragments (type III collagen degradation [C3M], type III collagen formation [PRO-C3], and type VI collagen formation [PRO-C6]), reflecting fibrogenesis and fibrolysis, with clinical outcomes in ADPKD.\n\nMethods: We included 302 patients from the DIPAK-1 trial (lanreotide vs. standard treatment), with a mean baseline age of 48.9 ± 7.3 years and estimated glomerular filtration rate (eGFR) of 51.3 ± 11.5 ml/min per 1.73 m2. Kidney endpoints were eGFR slope, rapid disease progression (eGFR loss ≥3 ml/min per 1.73 m2 per year), and a composite kidney endpoint (30% eGFR loss or initiation of kidney replacement therapy). Net benefit analysis was performed to assess clinical utility.\n\nResults: During 2.4 ± 0.4 years of follow-up, mean eGFR slope was −4.02 ± 3.64 ml/min per 1.73 m2 per year, 190 patients (62.9%) had rapid disease progression, and 87 (28.8%) reached the composite endpoint. After adjustment for sex, baseline age, baseline eGFR, Mayo imaging class (MIC), PKD pathogenic variant and treatment group, uPRO-C3/Cr and uPRO-C6/Cr were independently associated with eGFR slope, rapid disease progression, and the composite endpoint. uPRO-C3/Cr was also associated with HtTKV growth rate. Adding uPRO-C3/Cr or uPRO-C6/Cr improved prediction of rapid disease progression, increasing area under curve (AUC) from 0.78 (95% confidence interval [CI], 0.73–0.86) to 0.79 (95% CI, 0.73–0.86) and 0.80 (95% CI, 0.73–0.86), respectively. Decision curve analysis did not show a meaningful net benefit.\n\nConclusion: These findings demonstrate that uPRO-C3/Cr and uPRO-C6/Cr were independently associated with kidney outcomes in ADPKD, providing clinical evidence that extracellular matrix (ECM) remodeling is associated with ADPKD disease progression.",
  "abstract_shown": true,
  "affiliations": [
    "Cardiovascular & Renal Research, Nordic Bioscience, Herlev, Denmark",
    "Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Solveig Skovlund Groen"
    },
    {
      "affs": [
        1
      ],
      "name": "Ron T. Gansevoort"
    },
    {
      "affs": [
        0
      ],
      "name": "Nadja Sparding"
    },
    {
      "affs": [
        1
      ],
      "name": "Judith E. Heida"
    },
    {
      "affs": [
        1
      ],
      "name": "Esther Meijer"
    },
    {
      "affs": [
        0
      ],
      "name": "Morten A. Karsdal"
    },
    {
      "affs": [
        0
      ],
      "name": "Peder Frederiksen"
    },
    {
      "affs": [
        0
      ],
      "name": "Federica Genovese"
    },
    {
      "affs": [
        1
      ],
      "name": "Thomas Bais"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7b55jy7q6tpm5.bib",
  "cited_by": 0,
  "doi": "10.1016/j.ekir.2026.107102",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13733330/",
  "id": "7b55jy7q6tpm5",
  "issns": [
    "2468-0249"
  ],
  "landing_url": "https://doi.org/10.1016/j.ekir.2026.107102",
  "language": "en",
  "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": [
    [
      "heading",
      "Clinical Research"
    ],
    [
      "openalex",
      "1311|Genetic and Kidney Cyst Diseases"
    ]
  ],
  "openalex": "W7214064276",
  "pdf_url": null,
  "pmcid": "PMC13733330",
  "pmid": "42985540",
  "published": "2026-09-23",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/7b55jy7q6tpm5.ris",
  "sources": [
    {
      "first_seen": "2026-11-08T12:23:08Z",
      "native_id": "PMC13733330",
      "source": "pmc",
      "url": "https://doi.org/10.1016/j.ekir.2026.107102"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1311|Genetic and Kidney Cyst Diseases",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "Fibrogenesis Biomarkers and Clinical Disease Progression in ADPKD",
  "title_text": "Fibrogenesis Biomarkers and Clinical Disease Progression in ADPKD",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:23:08Z",
  "url": "https://research.draconitic.com/paper/7b55jy7q6tpm5",
  "venue": "Kidney International Reports",
  "versions": []
}