Recent Progress of the ARegPKD Registry Study on Autosomal Recessive Polycystic Kidney Disease.

Kathrin Ebner,Franz Schaefer,Max Christoph Liebau

doi:10.3389/fped.2017.00018

Abstract

Autosomal recessive polycystic kidney disease (ARPKD) is a rare monogenic disease with a severe phenotype often presenting prenatally or in early childhood. With its obligate renal and hepatic involvement, ARPKD is one of the most important indications for liver and/or kidney transplantation in childhood. Marked phenotypic variability is observed, the genetic basis of which is largely unknown. Treatment is symptomatic and largely empiric as evidence-based guidelines are lacking. Therapeutic initiatives for ARPKD face the problem of highly variable cohorts and lack of clinical or biochemical risk markers without clear-cut clinical end points. ARegPKD is an international, multicenter, retro- and prospective, observational study to deeply phenotype patients with the clinical diagnosis of ARPKD. Initiated in 2013 as a web-based registry (www.aregpkd.org), ARegPKD enrolls patients across large parts of Europe and neighboring countries. By January 2017, more than 400 patients from 17 mostly European countries have been registered in the ARPKD registry study with significant follow-up data. Due to comprehensive retro- and prospective data collection and associated biobanking, ARegPKD will generate a unique ARPKD cohort with detailed longitudinal clinical characterization providing a basis for future clinical trials as well as translational research. Hence, ARegPKD is hoped to contribute to the pathophysiological understanding of the disease and to the improvement of clinical management.

Highlights

Autosomal recessive polycystic kidney disease (ARPKD) is a severe form of polycystic kidney disease with early manifestation and substantial morbidity and mortality
Autosomal recessive polycystic kidney disease is caused by mutations in a single gene, polycystic kidney and hepatic disease 1 (PKHD1), encoding the ciliary protein fibrocystin/polyductin [2]
Even up to 20% of siblings show marked variance in phenotype [9], indicating that the genotype alone is not sufficient to explain the phenotypic variability in ARPKD [9, 14]

Summary

BACKGROUND

Autosomal recessive polycystic kidney disease (ARPKD) is a severe form of polycystic kidney disease with early manifestation and substantial morbidity and mortality. Despite the much more severe phenotype of ARPKD with progression to end-stage renal disease of the majority of the patients within the first two decades of life [9] [as compared to 58.1 years (PKD1) and 79.9 years (PKD2) in ADPKD [26]], the large individual phenotypic variability and the 40-fold lower incidence of ARPKD relative to ADPKD have so far precluded the development of clinical trial programs to evaluate the usefulness of compounds interfering with cyst growth. E.g., by Guay-Woodford and Desmond [27], Bergmann et al [9], and Adeva et al [13], have described the clinical course of individuals with ARPKD in European and North American cohorts Despite these excellent previous works, numerous questions remain regarding longterm clinical outcomes, the relative efficacy of current symptomatic treatment approaches, and the most suitable criteria to define risk-based cohort stratification in future interventional trials. We report about the current state of progress of this study

DESIGN

CURRENT STATUS

ARegPKD CONSORTIUM

Findings

ETHICS STATEMENT