Autosomal dominant polycystic kidney disease: an overview of recent genetic and clinical advances

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common inherited kidney disease, characterized by the progressive development of multiple kidney cysts, leading to a gradual decline in kidney function. ADPKD is also the fourth leading cause of kidney failure (KF) in adults. In addition to kidney manifestations, ADPKD is associated with various extrarenal features, including liver cysts, cardiovascular abnormalities, intracranial aneurysms, and chronic pain with significant impact on patients’ quality of life. While several disease-modifying agents have been tested in ADPKD, tolvaptan remains the only approved drug by the US Food and Drug Administration. The Mayo Imaging Classification is currently the most practical tool for predicting rate of kidney disease progression in ADPKD. This review provides a comprehensive overview of ADPKD, focusing on its genetics, pathophysiology, clinical presentation, management, and prognostic tools. Advances in diagnostic imaging and genetic testing have improved the early detection of ADPKD, allowing better classification of patients and prediction of KF. The review also discusses current therapeutic approaches to ADPKD, including tolvaptan, a vasopressin V2-receptor antagonist. Additionally, we address specific issues in children and pregnant individuals with ADPKD. Despite substantial progress in understanding ADPKD, there is a large need for additional effective treatments and prognostic markers to provide a more personalized care for these patients.

常染色体显性遗传性多囊肾病（Autosomal Dominant Polycystic Kidney Disease, ADPKD）是最常见的遗传性肾脏疾病，以肾脏多发囊肿进行性发展为特征，最终引发肾功能渐进性衰退。ADPKD同时也是成人肾衰竭（Kidney Failure, KF）的第四大常见病因。除肾脏相关临床表现外，ADPKD还可伴随多种肾外表现，包括肝囊肿、心血管异常、颅内动脉瘤以及严重影响患者生活质量的慢性疼痛。目前已有多款疾病修饰治疗药物在ADPKD中开展临床试验，但托伐普坦（tolvaptan）仍是唯一获得美国食品药品监督管理局（US Food and Drug Administration）批准的治疗药物。梅奥影像分类系统（Mayo Imaging Classification）是当前用于预测ADPKD患者肾病进展速率的最实用工具。本综述对ADPKD进行了全面概述，重点涵盖其遗传学、病理生理学、临床表现、治疗管理及预后评估工具。诊断影像学与基因检测技术的进步，推动了ADPKD的早期检出，助力实现更精准的患者分层与肾衰竭风险预测。本综述同时探讨了ADPKD的当前治疗方案，包括血管加压素V2受体拮抗剂托伐普坦。此外，本文还针对儿童与妊娠期ADPKD患者的特殊诊疗问题展开讨论。尽管目前对ADPKD的认知已取得显著进展，但仍亟需更多有效的治疗手段与预后标志物，以实现此类患者的个体化精准诊疗。