ARPKD (autosomal recessive polycystic kidney disease) is a clinical diagnosis that is suggested by characteristic hepatorenal involvement and a pedigree consistent with autosomal-recessive inheritance.
Kidney manifestations There is a large spectrum of severity with regards to renal involvement. Severe cases may present prenatally with oligohydramnios and enlarged echogenic kidneys on foetal ultrasound. In milder cases, renal cysts may be detected incidentally later in life and some patients only have exclusive liver involvement without apparent renal disease. If biopsied (not usually recommended), kidney cysts are seen exclusively in the collecting duct, remain in contact with their nephron of origin and are caused by abnormalities in tubular cell proliferation and fluid secretion. In patients with pre- or neonatal presentations, pulmonary hypoplasia can be a prominent finding and is a key factor determining early survival. Abdominal distention from the dramatically enlarged kidneys with consequent feeding problems is another common complication. Other potential complications include hyponatraemia, especially in infancy and likely reflecting impaired urinary dilution, as well as hypertension. Liver manifestations Liver manifestations can also have a large spectrum of severity. All patients have some degree of hepatic fibrosis. Imaging studies may show dilated biliary tracts. If biopsied (not usually recommended), ductal plate malformation is seen. If severe, portal hypertension with all its complications can develop. Another feared complication is ascending cholangitis, presenting as recurrent sepsis with enteric organisms.
There is no specific treatment for ARPKD. Care for affected patients should be provided in specialised centres with expertise in the disorder. Severe cases should be assessed for isolated or combined liver and kidney transplantation.
ARPKD is rare (~1:20,000 births), caused by recessive mutations in the gene PKHD1. Mutations in other genes may mimic the phenotype of ARPKD. Genetic testing is not usually needed to establish the diagnosis, but can help clarify the diagnosis in atypical cases and informs genetic counselling. Genetic testing for ARPKD is done through the UK Genetics testing network.
International Consensus Guidelines for the diagnosis and management of ARPKD have now been published. Information is also available on our international partner’s website, the US Hepato/Renal Fibrocystic Diseases Translational Resource, led by Prof Lisa Guay-Woodford.