Groopman Emily, Milo Rasouly Hila
Pediatrics and Medical Genetics Combined Residency Program, Children's National Hospital, Washington, DC, USA.
Division of Nephrology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, USA.
Kidney Int Rep. 2024 Dec 27;10(3):673-695. doi: 10.1016/j.ekir.2024.12.020. eCollection 2025 Mar.
Technological advances such as next-generation sequencing (NGS) have enabled high-throughput assessment of the human genome, supporting the usage of genetic testing as a first-line tool across clinical medicine. Although individually rare, genetic causes account for end-stage renal disease in 10% to 15% of adults and 70% of children, and in many of these individuals, genetic testing can identify a specific etiology and meaningfully impact management. However, with numerous options for genetic testing available, nephrologists may feel uncomfortable integrating genetics into their clinical practice. Here, we aim to demystify the process of genetic test selection and highlight the opportunities for interdisciplinary collaboration between nephrologists and genetics professionals, thereby supporting precision medicine for patients with kidney disease. We first detail the various clinical genetic testing modalities, highlighting their technical advantages and limitations, and then discuss indications for their usage. Next, we provide a generalized workflow for genetic test selection among individuals with kidney disease and illustrate how this workflow can be applied to genetic test selection across diverse clinical contexts. We then discuss key areas related to the usage of genetic testing in clinical nephrology that merit further research and approaches to investigate them.
诸如新一代测序（NGS）等技术进步使得对人类基因组进行高通量评估成为可能，这支持了基因检测作为临床医学一线工具的使用。尽管个体病例罕见，但遗传因素在10%至15%的成年终末期肾病患者以及70%的儿童终末期肾病患者中起着作用，并且在许多此类患者中，基因检测能够确定具体病因并对治疗管理产生重大影响。然而，由于基因检测有众多选择，肾病学家可能会对将遗传学融入临床实践感到不自在。在此，我们旨在揭开基因检测选择过程的神秘面纱，并强调肾病学家与遗传学专业人员之间跨学科合作的机会，从而为肾病患者提供精准医疗支持。我们首先详细介绍各种临床基因检测方式，突出其技术优势和局限性，然后讨论其使用指征。接下来，我们为肾病患者的基因检测选择提供一个通用流程，并说明该流程如何应用于不同临床背景下的基因检测选择。然后，我们讨论临床肾病学中与基因检测使用相关的值得进一步研究的关键领域以及研究这些领域的方法。
