PKDNet - ARPKD Learning Network - PROJECT SUMMARY / ABSTRACT Autosomal recessive polycystic kidney disease (ARPKD) is a rare disease, affecting ~1,500 children and young adults in the U.S. In severely affected patients, ARPKD can present in the neonatal period with massively enlarged kidneys and pulmonary hypoplasia, but the clinical spectrum of ARPKD is highly variable. We now recognize that just ~50% of patients present perinatally, and many present later in childhood or even adulthood. ARPKD causes progressive chronic kidney disease leading to kidney failure, as well as congenital hepatic fibrosis, which can lead to intrahepatic bile duct dilatation, periportal fibrosis, and portal hypertension. Despite this high burden of morbidity, there are currently no FDA-approved disease-modifying therapies for ARPKD. Several drugs appear promising in animal studies, but only one small Phase 1 clinical trial has been completed. Barriers to conducting clinical trials in ARPKD include: (1) limited natural history data; (2) lack of defined clinical outcomes to serve as trial endpoints; (3) lack of validated prognostic biomarkers to identify patients at highest risk of progression; and (4) difficulty in recruiting sufficient numbers of patients who are eligible, able, and willing to participate in trials. The overall objective of this proposal is to accelerate clinical trials for ARPKD by creating PKDnet, a robust data resource to identify a research-ready cohort of children with ARPKD and efficiently collect high quality, large-scale natural history data and identify suitable endpoints and prognostic biomarkers to inform clinical trial design. Data will come from PEDSnet, a National Pediatric Learning Health System with >14 years of electronic health record data for >13 million children at 11 U.S. academic pediatric centers. To inform future trial design, we will also leverage the PEDSnet infrastructure to administer patient and family surveys to identify priorities for patient-reported and clinical outcomes and understand factors affecting willingness to participate in clinical trials. Once established, PKDnet will serve as a sustainable resource for ARPKD research that will allow ongoing analysis of longitudinal natural history data, provide valuable data to inform future clinical trial design, and facilitate future recruitment of patients into high-priority studies.
