Estimating risk of rapid disease progression in pediatric patients with autosomal dominant polycystic kidney disease: a randomized trial of tolvaptan.

Background: Tolvaptan preserves kidney function in adults with autosomal dominant polycystic kidney disease (ADPKD) at elevated risk of rapid progression. A trial (NCT02964273) evaluated tolvaptan safety and pharmacodynamics in children (5–17 years). However, progression risk was not part of study e...

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Publicado en:Pediatric Nephrology Vol. 39; no. 5; pp. 1481 - 1491
Autores principales: Mekahli, Djalila, Guay-Woodford, Lisa M., Cadnapaphornchai, Melissa A., Goldstein, Stuart L., Dandurand, Ann, Jiang, Huan, Jadhav, Pravin, Debuque, Laurie
Formato: research tables/charts Journal Article
Publicado: Springer Nature May2024
Acceso en línea:Ver este registro en EBSCOhost
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      dt: May2024
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        10.1007/s00467-023-06239-8
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        atl: Estimating risk of rapid disease progression in pediatric patients with autosomal dominant polycystic kidney disease: a randomized trial of tolvaptan.
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          Mekahli, Djalila
          Guay-Woodford, Lisa M.
          Cadnapaphornchai, Melissa A.
          Goldstein, Stuart L.
          Dandurand, Ann
          Jiang, Huan
          Jadhav, Pravin
          Debuque, Laurie
        affil: https://ror.org/05f950310 PKD Research Group, Laboratory of Ion Channel Research, Department of Cellular and Molecular Medicine, KU Leuven, Louvain, Belgium
      sug:
        subj:
          Risk Assessment
          Disease Progression Risk Factors
          Polycystic Kidney, Autosomal Dominant Drug Therapy
          Polycystic Kidney, Autosomal Dominant Drug Therapy
          Vasopressins Antagonists and Inhibitors
          Receptors, Cell Surface Antagonists and Inhibitors
          Funding Source
          Human
          Child, Preschool
          Child
          Adolescence
          Retrospective Design
          Vasopressins Pharmacodynamics
          Vasopressins Adverse Effects
          Scales
          Male
          Female
          Confidence Intervals
          Descriptive Statistics
          Glomerular Filtration Rate
          Comparative Studies
          Child, Preschool: 2-5 years
          Child: 6-12 years
          Adolescent: 13-18 years
          Male
          Female
      ab: Background: Tolvaptan preserves kidney function in adults with autosomal dominant polycystic kidney disease (ADPKD) at elevated risk of rapid progression. A trial (NCT02964273) evaluated tolvaptan safety and pharmacodynamics in children (5–17 years). However, progression risk was not part of study eligibility criteria due to lack of validated criteria for risk assessment in children. As risk estimation is important to guide clinical management, baseline characteristics of the study participants were retrospectively evaluated to determine whether risk of rapid disease progression in pediatric ADPKD can be assessed and to identify parameters relevant for risk estimation. Methods: Four academic pediatric nephrologists reviewed baseline data and rated participant risk from 1 (lowest) to 5 (highest) based on clinical judgement and the literature. Three primary reviewers independently scored all cases, with each case reviewed by two primary reviewers. For cases with discordant ratings (≥ 2-point difference), the fourth reviewer provided a secondary rating blinded to the primary evaluations. Study participants with discordant ratings and/or for whom data were lacking were later discussed to clarify parameters relevant to risk estimation. Results: Of 90 evaluable subjects, primary reviews of 69 (77%) were concordant. The proportion considered at risk of rapid progression (final mean rating ≥ 3.5) by age group was: 15–17 years, 27/34 (79%); 12– < 15, 9/32 (28%); 4– < 12, 8/24 (33%). The panelists agreed on characteristics important for risk determination: age, kidney imaging, kidney function, blood pressure, urine protein, and genetics. Conclusions: High ratings concordance and agreement among reviewers on relevant clinical characteristics support the feasibility of pediatric risk assessment. A higher resolution version of the Graphical abstract is available as Supplementary information
      pubtype: Academic Journal
      doctype:
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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