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Open Access 13-12-2023 | Polycystic Kidney Disease | Original Article

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

Authors: Djalila Mekahli, Lisa M. Guay-Woodford, Melissa A. Cadnapaphornchai, Stuart L. Goldstein, Ann Dandurand, Huan Jiang, Pravin Jadhav, Laurie Debuque

Published in: Pediatric Nephrology | Issue 5/2024

Abstract

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.

Graphical abstract

A higher resolution version of the Graphical abstract is available as Supplementary information

Available only for authorised users

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Title: Estimating risk of rapid disease progression in pediatric patients with autosomal dominant polycystic kidney disease: a randomized trial of tolvaptan
Authors: Djalila Mekahli
Lisa M. Guay-Woodford
Melissa A. Cadnapaphornchai
Stuart L. Goldstein
Ann Dandurand
Huan Jiang
Pravin Jadhav
Laurie Debuque
Publication date: 13-12-2023
Publisher: Springer Berlin Heidelberg
Keywords: Polycystic Kidney Disease
Chronic Kidney Disease
Published in: Pediatric Nephrology / Issue 5/2024
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI: https://doi.org/10.1007/s00467-023-06239-8

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Background

Methods

Results

Conclusions

Graphical abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Graphical abstract

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