Vendrig Lisanne M, Ten Hoor Mayke A C, König Benthe H, Lekkerkerker Iris, Renkema Kirsten Y, Schreuder Michiel F, van der Zanden Loes F M, van Eerde Albertien M, Groen In 't Woud Sander, Mulder Jaap, Westland Rik
Department of Pediatric Nephrology, Amsterdam UMC-Emma Children's Hospital, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
Division of Nephrology, Department of Pediatrics, Willem-Alexander Children's Hospital, Leiden University Medical Center, Leiden, The Netherlands.
Pediatr Nephrol. 2025 Mar;40(3):685-699. doi: 10.1007/s00467-024-06479-2. Epub 2024 Oct 7.
While up to 50% of children requiring kidney replacement therapy have congenital anomalies of the kidney and urinary tract (CAKUT), they represent only a fraction of the total patient population with CAKUT. The extreme variability in clinical outcome underlines the fundamental need to devise personalized clinical management strategies for individuals with CAKUT. Better understanding of the pathophysiology of abnormal kidney and urinary tract development provides a framework for precise diagnoses and prognostication of patients, the identification of biomarkers and disease modifiers, and, thus, the development of personalized strategies for treatment. In this review, we provide a state-of-the-art overview of the currently known genetic causes, including rare variants in kidney and urinary tract development genes, genomic disorders, and common variants that have been attributed to CAKUT. Furthermore, we discuss the impact of environmental factors and their interactions with developmental genes in kidney and urinary tract malformations. Finally, we present multi-angle translational modalities to validate candidate genes and environmental factors and shed light on future strategies to better understand the molecular underpinnings of CAKUT.
虽然高达50% 需要肾脏替代治疗的儿童患有先天性肾脏和尿路异常（CAKUT），但他们仅占CAKUT患者总数的一小部分。临床结果的极端变异性凸显了为CAKUT患者制定个性化临床管理策略的根本必要性。对肾脏和尿路发育异常的病理生理学有更好的了解，为精确诊断和预测患者、识别生物标志物和疾病修饰因子提供了框架，从而为制定个性化治疗策略提供了依据。在本综述中，我们提供了当前已知遗传病因的最新概述，包括肾脏和尿路发育基因中的罕见变异、基因组疾病以及与CAKUT相关的常见变异。此外，我们讨论了环境因素的影响及其与肾脏和尿路畸形发育基因的相互作用。最后，我们提出多角度转化模式，以验证候选基因和环境因素，并阐明未来策略，以更好地理解CAKUT的分子基础。
