{
  "abstract": "Introduction\n\nTolvaptan is indicated for adults with autosomal dominant polycystic kidney disease (ADPKD) at increased risk of rapid progression. Pharmacodynamic activity and acceptable safety and tolerability were demonstrated in a 1-year, randomized, placebo-controlled trial in children and adolescents with ADPKD (Phase A of a 2-part, phase-3b study [NCT02964273]). Here, the 2-year, open-label extension (Phase B) is reported.Methods\n\nPhase A participants could enter Phase B if they had not experienced adverse events requiring discontinuation. All Phase B participants received tolvaptan, titrated based on body weight and tolerability. Outcomes included safety, tolerability, kidney function, height-adjusted total kidney volume (htTKV), and health-related quality of life (HRQoL).Results\n\nOf 84 Phase A completers, 81 enrolled in Phase B. No liver enzyme elevations observed in either phase met criteria for drug-induced liver injury. The previous placebo group experienced more aquaresis-related (48.7% vs. 14.3%) and dehydration-related (28.2% vs. 14.3%) adverse events than the previous tolvaptan group in Phase B. Tolerability was favorable, with HRQoL outcomes indicating high functioning in both the trial phases. Estimated glomerular filtration rate (eGFR) remained stable in the tolvaptan arm and decreased in the placebo arm of Phase A (annual slope in ml/min per 1.73 m² of 2.4 and -2.2, respectively [P = 0.04]), with similar slopes of decline for both arms of Phase B (-1.3 in the prior tolvaptan arm and -2.1 in the prior placebo arm [P = 0.54]). htTKV growth was slowest during the first year of tolvaptan treatment.Conclusion\n\nTolvaptan-related safety and overall HRQoL remained favorable, and kidney function was stable in this 2-year extension. The slowest htTKV growth occurred during year 1 of tolvaptan treatment.",
  "abstract_shown": true,
  "affiliations": [
    "PKD Research Group, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.",
    "Department of Pediatric Nephrology, University Hospitals Leuven, Leuven, Belgium.",
    "Division of Nephrology, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadephia, Pennsylvania, USA.",
    "Children's National Research Institute, Washington, DC, USA.",
    "Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, Georgia, USA.",
    "Children's Memorial Health Institute, Warsaw, Poland.",
    "Department of Pediatrics, 2nd Medical Faculty, Charles University, Prague, Czech Republic.",
    "Department of Pediatrics, University Hospital Ostrava and Medical Faculty of University Ostrava, Ostrava, Czech Republic.",
    "Stoke Therapeutics, Inc, Bedford, Massachusetts, USA.",
    "Otsuka Pharmaceutical Development & Commercialization, Inc, Princeton, New Jersey, USA.",
    "Otsuka Pharmaceutical Development & Commercialization, Inc, Rockville, Maryland, USA.",
    "Center for Pediatrics and Adolescent Medicine, Heidelberg, Germany."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Djalila Mekahli"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Lisa M Guay-Woodford"
    },
    {
      "affs": [
        2
      ],
      "name": "Melissa A Cadnapaphornchai"
    },
    {
      "affs": [
        4
      ],
      "name": "Larry A Greenbaum"
    },
    {
      "affs": [
        5
      ],
      "name": "Mieczyslaw Litwin"
    },
    {
      "affs": [
        6,
        7
      ],
      "name": "Tomas Seeman"
    },
    {
      "affs": [
        8,
        9
      ],
      "name": "Ann Dandurand"
    },
    {
      "affs": [
        9
      ],
      "name": "Zhen Zhang"
    },
    {
      "affs": [
        10
      ],
      "name": "Kimberly Sikes"
    },
    {
      "affs": [
        9
      ],
      "name": "Susan E Shoaf"
    },
    {
      "affs": [
        11
      ],
      "name": "Franz Schaefer"
    },
    {
      "name": "Pediatric Trial Investigators13"
    },
    {
      "name": "Pediatric Trial Investigators"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6a55455ngpacp.bib",
  "cited_by": 0,
  "doi": "10.1016/j.ekir.2026.107077",
  "fulltext_url": "https://europepmc.org/articles/PMC13688458",
  "id": "6a55455ngpacp",
  "issns": [
    "2468-0249"
  ],
  "landing_url": "https://europepmc.org/article/MED/42923342",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1311|Genetic and Kidney Cyst Diseases"
    ]
  ],
  "openalex": "W7213244870",
  "pdf_url": "https://europepmc.org/articles/PMC13688458?pdf=render",
  "pmcid": "PMC13688458",
  "pmid": "42923342",
  "published": "2026-09-15",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/6a55455ngpacp.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:21:02Z",
      "native_id": "MED:42923342",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42923342"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1311|Genetic and Kidney Cyst Diseases",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "Clinical Trial of Tolvaptan in Pediatric ADPKD: Two-Year, Open-Label Extension.",
  "title_text": "Clinical Trial of Tolvaptan in Pediatric ADPKD: Two-Year, Open-Label Extension.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:21:02Z",
  "url": "https://research.draconitic.com/paper/6a55455ngpacp",
  "venue": "Kidney international reports",
  "versions": []
}