Division of Nephrology, Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA.
Division of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Kidney Int. 2024 Feb;105(2):218-230. doi: 10.1016/j.kint.2023.11.018.
Glomerular diseases are classified using a descriptive taxonomy that is not reflective of the heterogeneous underlying molecular drivers. This limits not only diagnostic and therapeutic patient management, but also impacts clinical trials evaluating targeted interventions. The Nephrotic Syndrome Study Network (NEPTUNE) is poised to address these challenges. The study has enrolled >850 pediatric and adult patients with proteinuric glomerular diseases who have contributed to deep clinical, histologic, genetic, and molecular profiles linked to long-term outcomes. The NEPTUNE Knowledge Network, comprising combined, multiscalar data sets, captures each participant's molecular disease processes at the time of kidney biopsy. In this editorial, we describe the design and implementation of NEPTUNE Match, which bridges a basic science discovery pipeline with targeted clinical trials. Noninvasive biomarkers have been developed for real-time pathway analyses. A Molecular Nephrology Board reviews the pathway maps together with clinical, laboratory, and histopathologic data assembled for each patient to compile a Match report that estimates the fit between the specific molecular disease pathway(s) identified in an individual patient and proposed clinical trials. The NEPTUNE Match report is communicated using established protocols to the patient and the attending nephrologist for use in their selection of available clinical trials. NEPTUNE Match represents the first application of precision medicine in nephrology with the aim of developing targeted therapies and providing the right medication for each patient with primary glomerular disease.
肾小球疾病采用描述性分类法进行分类,这种分类法不能反映潜在的异质分子驱动因素。这不仅限制了诊断和治疗患者管理,也影响了评估靶向干预的临床试验。肾病综合征研究网络(NEPTUNE)正准备应对这些挑战。该研究招募了 850 多名患有蛋白尿性肾小球疾病的儿科和成年患者,他们提供了与长期结果相关的深入临床、组织学、遗传和分子特征。由多尺度数据集组成的 NEPTUNE 知识网络,在肾脏活检时捕获每个参与者的分子疾病过程。在这篇社论中,我们描述了 NEPTUNE Match 的设计和实施,它将基础科学发现管道与靶向临床试验联系起来。已经开发了非侵入性生物标志物用于实时途径分析。分子肾病委员会与为每位患者汇编的临床、实验室和组织病理学数据一起审查途径图,以编制一份匹配报告,该报告估计个体患者中特定分子疾病途径与拟议临床试验之间的匹配程度。使用既定协议将 NEPTUNE Match 报告传达给患者和主治肾病学家,以便他们选择可用的临床试验。NEPTUNE Match 代表了肾脏病学中精准医学的首次应用,旨在开发靶向治疗方法,并为每位原发性肾小球疾病患者提供正确的药物。