Rationale, design and objectives of ARegPKD, a European ARPKD registry study

Abstract

BackgroundAutosomal recessive polycystic kidney disease (ARPKD) is a rare but frequently severe disorder that is typically characterized by cystic kidneys and congenital hepatic fibrosis but displays pronounced phenotypic heterogeneity. ARPKD is among the most important causes for pediatric end stage renal disease and a leading reason for liver-, kidney- or combined liver kidney transplantation in childhood. The underlying pathophysiology, the mechanisms resulting in the observed clinical heterogeneity and the long-term clinical evolution of patients remain poorly understood. Current treatment approaches continue to be largely symptomatic and opinion-based even in most-advanced medical centers. While large clinical trials for the frequent and mostly adult onset autosomal dominant polycystic kidney diseases have recently been conducted, therapeutic initiatives for ARPKD are facing the challenge of small and clinically variable cohorts for which reliable end points are hard to establish.Methods/DesignARegPKD is an international, mostly European, observational study to deeply phenotype ARPKD patients in a pro- and retrospective fashion. This registry study is conducted with the support of the German Society for Pediatric Nephrology (GPN) and the European Study Consortium for Chronic Kidney Disorders Affecting Pediatric Patients (ESCAPE Network). ARegPKD clinically characterizes long-term ARPKD courses by a web-based approach that uses detailed basic data questionnaires in combination with yearly follow-up visits. Clinical data collection is accompanied by associated biobanking and reference histology, thus setting roots for future translational research.DiscussionThe novel registry study ARegPKD aims to characterize miscellaneous subcohorts and to compare the applied treatment options in a large cohort of deeply characterized patients. ARegPKD will thus provide evidence base for clinical treatment decisions and contribute to the pathophysiological understanding of this severe inherited disorder.

Clinical and Genetic Characteristics of Autosomal Recessive Polycystic Kidney Disease in Oman

“…Such effort can elaborate the current understanding of ARPKD and deliver more information on extrarenal manifestations and treatment options. Recently, the German Society for Pediatric Nephrology (GPN) and the European Study Consortium for Chronic Kidney Disorders Affecting Pediatric Patients (ESCAPE) collaborated to initiate an international multicenter registry of ARPKD (ARegPKD) [42]. The continued identi cation of PKHD1 variants and their associated phenotypes is to be promoted and inclusion of cohorts from different ethnicities is valuable and should be encouraged.…”

Gastrostomy Tube Insertion in Pediatric Patients With Autosomal Recessive Polycystic Kidney Disease (ARPKD): Current Practice

“…Due to the concomitant hepatorenal affection, children with ARPKD rely on a multidisciplinary collaboration of both pediatric nephrologists and gastroenterologists/hepatologists ( 22 ). In order to set a basis for development of management recommendations in a multidisciplinary approach, international initiatives like the recently established ARPKD registry Study ARegPKD will further help to define indications and contraindications of gastrostomy insertion in ARPKD patients ( 23 , 24 ).…”

Network for Early Onset Cystic Kidney Diseases—A Comprehensive Multidisciplinary Approach to Hereditary Cystic Kidney Diseases in Childhood

“…Despite all the achievements mentioned above, enormous challenges remain to be solved: the complex phenotypic spectrum, genetic heterogeneity, a lack of reliable genotype–phenotype correlations, a limited molecular understanding and the absence of disease-specific biomarkers still hamper an early diagnosis and individual counseling. Data from international registry studies like the NEPHREG or the ARegPKD registry will certainly help to define robust genotype–phenotype associations by increasing sample sizes and following individual disease courses in a longitudinal fashion ( 10 , 37 ). However, in order to achieve a deeper clinical as well as molecular understanding, international collaborative efforts comprising various subspecialists will be necessary to move knowledge forward especially in the context of rare diseases.…”

“…Three pre-existing registries on NPH-RC, 1 BBS, and HNF1B were merged to build the fundaments of this new database. Additionally, technical bridgehead components have been implemented that allow a direct comparative data analysis with the international ARPKD registry 2 ( 37 ). Thereby, NEOCYST is the first registry study providing a comprehensive approach to early onset hereditary cystic kidney diseases and allowing back-to-back analyses on similarities and differences of the individual disease entities.…”