The packet contains no certified causative-gene claim and no certified inheritance-pattern field for this entry. GeneReviews notes that some data on ARPKD predate the understanding of its heterogeneous genetic causes, so its descriptions draw on cohorts with ARPKD in general as well as cohorts with a molecular diagnosis. GeneReviews reports that genotype-phenotype correlations have been observed based on the class and location of the pathogenic variant, and that no statistically significant differences in kidney survival during childhood and adolescence were found when subgroups defined by molecular diagnosis were compared. It adds that the genetic etiology may be relevant to the prognosis of kidney survival.

GeneReviews states that consensus expert guidance on the clinical diagnosis of ARPKD was published in 2014. It describes ultrasonography as the imaging method of choice for assessing the kidneys prenatally and in all pediatric age groups, because it is cost-effective, painless, widely available, and does not require radiation or sedation, and it notes that kidney biopsy is not used to diagnose ARPKD.

For perinatal presentation, GeneReviews describes prenatal imaging findings, frequent in the second half of pregnancy, of enlarged hyperechogenic kidneys with reduced corticomedullary differentiation, microcysts, and few or no macrocysts, a "salt-and-pepper appearance." Severe kidney involvement with oligohydramnios or anhydramnios can produce a Potter syndrome-like phenotype with pulmonary hypoplasia. In the neonatal period, abdominal distention from massive enlargement of the kidneys and liver can be evident, and kidney function ranges from limited impairment to kidney failure requiring dialysis.

For the liver, GeneReviews describes ultrasonography detecting hepatomegaly, inhomogeneous liver parenchyma, and dilated bile ducts or cystic changes. Magnetic resonance cholangiopancreatography is described as a sensitive assessment of biliary ductal anatomy, and, combined with kidney imaging findings, biliary duct anomalies are described as diagnostic of ARPKD and as having largely replaced liver biopsy. Liver function on standard laboratory tests is typically normal. Newborn-screening information is not certified in this packet.

The packet certifies no FDA-approved treatments, so approved-treatment coverage is unknown in this packet. GeneReviews states there is currently no cure for ARPKD and describes supportive care aimed at quality of life, function and fewer complications, ideally delivered through interdisciplinary and interprofessional care by specialists in relevant fields.

For perinatal and infantile presentation, GeneReviews describes initial management as focused on stabilizing pulmonary and kidney function. Pulmonary hypoplasia may call for non-invasive or invasive respiratory support, and extracorporeal membrane oxygenation is mentioned for individual cases. For massively enlarged kidneys, GeneReviews notes that some have advocated unilateral or bilateral nephrectomy, with limited supporting evidence; it lists risks of bilateral nephrectomy, including lifelong kidney replacement therapy and reports of hypotension linked to neurologic damage, and describes a very cautious approach to bilateral nephrectomy in the first months of life.

For significant chronic kidney disease, GeneReviews describes that children can be treated with modern pediatric kidney failure therapies, including dialysis and kidney transplantation, along with standard approaches to anemia, acidosis and mineral bone disease associated with chronic kidney disease. Peritoneal dialysis is described as the modality of choice for neonates with oliguria or anuria. Supplemental feeding or fluid therapy through a nasogastric or gastrostomy tube may be required, and hypertension can be severe enough to require multiple antihypertensive medications.

GeneReviews' surveillance section lists blood pressure measurement, with a target in the 50th percentile for children, and close follow-up of kidney function and chronic kidney disease complications by the treating pediatric nephrologist. Under investigation, GeneReviews describes animal-model studies of the multikinase inhibitor tesevatinib, with an initial phase I/II trial in infants and children whose results were unpublished at the time, and two multinational open-label phase III trials of tolvaptan.

No natural-history field is certified in this packet, and the information below is drawn from GeneReviews' clinical description. GeneReviews describes pulmonary hypoplasia as a major cause of neonatal morbidity and mortality, reports that respiratory support was required in 23% of infants (78 of 333) in a large retrospective European study, and notes that long-term pulmonary function appears good unless mechanical ventilation was required in the newborn period. It states that kidney failure is not the leading cause of neonatal demise and that the time course of kidney function varies widely. It also notes that the causative gene may be relevant to the prognosis of kidney survival.

The packet lists several active clinical studies for ARPKD. They include a phase III study of the safety of tolvaptan in infants and children, a database study of ARPKD, a national registry of rare kidney diseases, and a study on non-invasive prenatal diagnosis of single-gene disorders. Active clinical trials for this condition are listed on ClinicalTrials.gov.