Divisions of Nephrology and Genomic Medicine, University Health Network and University of Toronto, Toronto, Ontario, Canada.
Nephron Clin Pract. 2011;118(1):c19-30. doi: 10.1159/000320887. Epub 2010 Nov 11.
Autosomal dominant polycystic kidney disease (ADPKD) is the most common mendelian disorder of the kidney and accounts for ~5% of end-stage renal disease in North America. It is characterized by focal development of renal cysts which increase in number and size with age. Mutations of PKD1 and PKD2 account for most cases. Although the clinical manifestations of both gene types overlap completely, PKD1 is associated with more severe disease than PKD2, with larger kidneys and earlier onset of end-stage renal disease. Furthermore, marked within-family renal disease variability is well documented in ADPKD and suggests a strong modifier effect from as yet unknown genetic and environmental factors. In turn, the significant inter- and intra-familial renal disease variability poses a challenge for diagnosis and genetic counseling. In general, renal ultrasonography is commonly used for the diagnosis, and age-dependent criteria have been defined for subjects at risk of PKD1. However, the utility of the PKD1 ultrasound criteria in the clinical setting is unclear since their performance characteristics have not been defined for the milder PKD2 and the gene type for most test subjects is unknown. Recently, highly predictive ultrasound diagnostic criteria have been derived for at-risk subjects of unknown gene type. Additionally, both DNA linkage and gene-based direct sequencing are available for the diagnosis of ADPKD, especially in subjects with equivocal imaging results, a negative or indeterminate family history, or in younger at-risk individuals being evaluated as potential living related kidney donor. This review will highlight the utility and limitations of clinical predictors of gene types, imaging- and molecular-based diagnostic tests, and present an integrated approach for evaluating individuals suspected to have ADPKD.
常染色体显性多囊肾病（ADPKD）是最常见的肾脏常染色体显性遗传疾病，约占北美终末期肾病的 5%。其特征是肾脏囊肿的局灶性发展，随着年龄的增长，囊肿数量和大小逐渐增加。PKD1 和 PKD2 的突变占大多数病例。尽管两种基因突变类型的临床表现完全重叠，但 PKD1 与 PKD2 相比，疾病更为严重，肾脏更大，终末期肾病的发病更早。此外，ADPKD 中明确记录了家族内肾脏疾病的显著变异性，表明存在未知遗传和环境因素的强烈修饰效应。反过来，ADPKD 中显著的家族内和家族间肾脏疾病变异性对诊断和遗传咨询构成了挑战。一般来说，肾脏超声检查常用于诊断，并且已经为 PKD1 风险患者定义了年龄依赖性标准。然而，PKD1 超声标准在临床环境中的实用性尚不清楚，因为尚未为更轻微的 PKD2 定义其性能特征，并且大多数检测对象的基因类型未知。最近，已经为未知基因类型的高危患者衍生出了高度预测性的超声诊断标准。此外，DNA 连锁和基于基因的直接测序均可用于 ADPKD 的诊断，尤其是在影像学结果不确定、家族史阴性或不确定或在评估作为潜在活体相关肾供体的年轻高危个体时。这篇综述将重点介绍基因类型的临床预测因子、影像学和分子诊断测试的实用性和局限性，并提出一种用于评估疑似 ADPKD 患者的综合方法。
