Dahmer-Heath Mareike, Optenhövel Sven, Hechler Tanja, Konrad Martin, König Jens
Department of General Pediatrics, University Children's Hospital Münster, Waldeyerstraße 22, 48149, Münster, Germany.
Department of Clinical Psychology and Psychotherapy for Children and Adolescents, University of Münster, Münster, Germany.
Pediatr Nephrol. 2025 Aug 20. doi: 10.1007/s00467-025-06912-0.
Nephronophthisis (NPH) is a rare hereditary cystic kidney disease, characterized by a highly variable clinical and genetic presentation, accounting for up to 10% of kidney failure in children. Despite advances in understanding its molecular basis and phenotypic spectrum, no causative therapies exist, and clinical trials remain absent. To support future treatment development, patient-reported outcome measures (PROMs) tailored to NPH should be defined to prioritize outcomes meaningful to patients and families.
This study aimed to analyze the use of clinical data, surrogate parameters, and patient-reported outcomes in NPH research to date, with a focus on the Standardized Outcomes in Nephrology (SONG) project outcomes validated for children with chronic kidney disease (SONG Kids).
A systematic search of the MEDLINE database was conducted for NPH studies.
Studies published after 1988, written in English, reporting at least one human clinical outcome, with a sample size of n ≥ 4, and using original data were considered eligible.
A total of 1066 records were retrieved through the search, of which 821 full-text reports were assessed for eligibility. Of these, 90 studies met eligibility criteria and were included in the review. While 100% of the studies reported clinical outcomes and 85% included surrogate parameter, only 41% examined patient-reported outcomes. Overlap between the SONG Kids outcome set and the outcomes identified in this study was moderate. Only 20 studies reported more than one SONG core outcome, while 24% and 66% of studies reported at least one middle tier or outer tier outcome, respectively. None of these studies used instruments validated for NPH.
The majority of studies focused primarily on molecular and genetic aspects, with clinical outcomes addressed only as a secondary consideration. The review incorporated only one prospective study, while the remaining studies were retrospective in nature. Differentiation between outcomes reported by children and those reported by parents was not possible in the included studies; this important distinction must be taken into account in the development of future PROMs for NPH.
Studies in NPH addressed both clinical outcomes and surrogate parameters, but there is a notable absence of measures related to life participation and patient-reported outcomes. Disease group-specific instruments fall short in adequately reflecting the symptoms of individual diseases, emphasizing the necessity for the development of disease-specific PROMs for NPH. Open Science Framework (OSF) registration: https://doi.org/10.17605/OSF.IO/658BR.
肾单位肾痨（NPH）是一种罕见的遗传性囊性肾病，其临床和基因表现高度可变，在儿童肾衰竭中占比高达10%。尽管在理解其分子基础和表型谱方面取得了进展，但尚无因果性治疗方法，也没有临床试验。为支持未来的治疗开发，应定义针对NPH的患者报告结局测量指标（PROMs），以优先考虑对患者和家庭有意义的结局。
本研究旨在分析迄今为止NPH研究中临床数据、替代参数和患者报告结局的使用情况，重点关注已在慢性肾病儿童中验证的肾脏病标准化结局（SONG）项目结局（SONG Kids）。
对MEDLINE数据库进行系统检索以查找NPH研究。
1988年后发表、用英文撰写、报告至少一项人类临床结局、样本量n≥4且使用原始数据的研究被视为合格。
通过检索共检索到1066条记录，其中821篇全文报告被评估是否符合纳入标准。其中，90项研究符合纳入标准并被纳入综述。虽然100%的研究报告了临床结局，85%纳入了替代参数，但只有41%研究了患者报告结局。SONG Kids结局集与本研究中确定的结局之间的重叠程度适中。只有20项研究报告了不止一项SONG核心结局，而分别有24%和66%的研究报告了至少一项中层或外层结局。这些研究均未使用针对NPH验证的工具。
大多数研究主要关注分子和基因方面，仅将临床结局作为次要考虑因素。该综述仅纳入了一项前瞻性研究，其余研究均为回顾性研究。在纳入的研究中无法区分儿童报告的结局和父母报告的结局；在未来开发NPH的PROMs时必须考虑这一重要区别。
NPH研究涉及临床结局和替代参数，但明显缺乏与生活参与和患者报告结局相关的测量指标。针对疾病组别的工具在充分反映个体疾病症状方面存在不足，强调了开发针对NPH的疾病特异性PROMs的必要性。开放科学框架（OSF）注册：https://doi.org/10.17605/OSF.IO/658BR。
