Alzarka Bakri, Morizono Hiroki, Bollman John W, Kim Dongkyu, Guay-Woodford Lisa M
Division of Nephrology, Children's National Health System, Washington, DC, USA.
Center for Genetic Medicine, Children's National Health System, Washington, DC, USA.
Front Pediatr. 2017 Apr 20;5:80. doi: 10.3389/fped.2017.00080. eCollection 2017.
Autosomal recessive polycystic kidney disease (ARPKD) and other hepatorenal fibrocystic diseases (HRFD) are relatively rare recessive disorders that constitute an important set of childhood nephropathies. Little is known about fundamental pathogenesis, and advances toward clinical trials will require well-characterized patient cohorts and the development of predictive and prognostic biomarkers. Such studies in rare diseases require greater collaboration than the efforts in common diseases where large patient repositories can be built at a single site. For the HRFD, clinical and translational research studies would be well served by centralized case accrual that coordinates collection of clinical data, biospecimens (DNA and tissues), and genetic information. As a part of the NIH-funded Hepatorenal Fibrocystic Disease Core Center, we have established a web-accessible portal to enroll patients with ARPKD and other HRFD and compile baseline and longitudinal clinical information in a REDCap-based clinical database. This central database is structured to collect clinical data from patients throughout the Americas (North, Central, and South). By using informatic analyses, we have defined the first data-driven estimates of ARPKD-related neonatal mortality, as well as the incidence and prevalence of this disease. These data indicate that while ARPKD is a rare disorder, there are hundreds of patients potentially available for deep clinical phenotyping in the United States alone. The centralization and sharing of clinical information and biomaterials from ARPKD and other HRFD patients hold the potential to accelerate progress in understanding disease pathways. Once the database is mature, the well-characterized patient cohorts will provide an important resource for developing clinical trials to evaluate new targeted therapeutic interventions in this spectrum of disorders.
常染色体隐性多囊肾病（ARPKD）和其他肝肾纤维囊性疾病（HRFD）是相对罕见的隐性疾病，是儿童肾病的重要组成部分。对其基本发病机制知之甚少，临床试验的进展将需要特征明确的患者队列以及预测和预后生物标志物的开发。罕见病的此类研究比常见疾病的研究需要更多的合作，因为常见疾病可以在单个地点建立大型患者资料库。对于HRFD，集中病例积累将有助于临床和转化研究，该积累可协调临床数据、生物样本（DNA和组织）以及遗传信息的收集。作为美国国立卫生研究院资助的肝肾纤维囊性疾病核心中心的一部分，我们建立了一个可通过网络访问的门户，用于招募ARPKD和其他HRFD患者，并在基于REDCap的临床数据库中汇编基线和纵向临床信息。这个中央数据库的构建目的是收集来自美洲各地（北美、中美和南美）患者的临床数据。通过信息分析，我们首次对ARPKD相关的新生儿死亡率以及该疾病的发病率和患病率进行了数据驱动的估计。这些数据表明，虽然ARPKD是一种罕见疾病，但仅在美国就有数百名患者可能适合进行深入的临床表型分析。集中和共享ARPKD和其他HRFD患者的临床信息和生物材料有可能加速我们对疾病途径的理解。一旦数据库成熟，特征明确的患者队列将为开展临床试验提供重要资源，以评估针对这一系列疾病的新靶向治疗干预措施。
