评估常染色体显性遗传多囊肾病患儿疾病快速进展风险：托伐普坦的一项随机试验。

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

机构信息

PKD Research Group, Laboratory of Ion Channel Research, Department of Cellular and Molecular Medicine, KU Leuven, Louvain, Belgium.

Department of Pediatric Nephrology, University Hospital of Leuven, Herestraat 49, B-3000, Louvain, Belgium.

出版信息

Pediatr Nephrol. 2024 May;39(5):1481-1490. doi: 10.1007/s00467-023-06239-8. Epub 2023 Dec 13.

DOI:10.1007/s00467-023-06239-8

PMID:38091246

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10942936/

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.

摘要

背景

托伐普坦可预防常染色体显性遗传多囊肾病（ADPKD）患者的肾功能恶化，这些患者存在快速进展的风险。一项试验（NCT02964273）评估了托伐普坦在儿童（5-17 岁）中的安全性和药效学。然而，由于缺乏儿童风险评估的验证标准，进展风险不是研究纳入标准的一部分。由于风险评估对于指导临床管理很重要，因此回顾性评估研究参与者的基线特征，以确定是否可以评估儿科 ADPKD 患者的快速疾病进展风险，并确定与风险评估相关的参数。

方法

4 位学术儿科肾病学家根据临床判断和文献回顾，对参与者的基线数据进行评估，并对每位参与者的风险进行 1（最低）至 5（最高）的评分。3 位主要审查员独立对所有病例进行评分，每位病例由两位主要审查员进行审查。对于评分差异（≥2 分）较大的病例，第 4 位审查员在不了解主要评估的情况下提供次要评分。对于评分不一致和/或数据缺失的病例，随后进行讨论以明确与风险评估相关的参数。

结果

在 90 例可评估的受试者中，69 例（77%）的主要评估结果一致。根据年龄组，被认为有快速进展风险（最终平均评分≥3.5）的比例为：15-17 岁，27/34（79%）；12-<15 岁，9/32（28%）；4-<12 岁，8/24（33%）。专家组一致认为以下特征对风险确定很重要：年龄、肾脏影像学、肾功能、血压、尿蛋白和遗传学。