Autosomal recessive polycystic kidney disease

Autosomal recessive polycystic kidney disease (ARPKD), also known as infantile polycystic kidney disease, is a rare inherited disorder that primarily affects the kidneys and liver. It is caused by mutations in the PKHD1 gene, which encodes a protein called fibrocystin (also known as polyductin). This protein plays a critical role in the normal development and function of kidney tubules and bile ducts. In ARPKD, the collecting ducts of the kidneys become dilated and filled with fluid, forming numerous small cysts that cause the kidneys to enlarge significantly. The liver is also affected, with characteristic congenital hepatic fibrosis and bile duct abnormalities (ductal plate malformation) that can lead to portal hypertension over time. The severity of ARPKD varies widely. In the most severe cases, the disease presents before birth or in the neonatal period with massively enlarged kidneys, reduced amniotic fluid (oligohydramnios), and underdeveloped lungs (pulmonary hypoplasia), which can be life-threatening. Affected newborns may have respiratory insufficiency and Potter sequence features. Infants and children who survive the neonatal period typically develop progressive chronic kidney disease, systemic hypertension (often severe and early-onset), and complications of hepatic fibrosis including portal hypertension with esophageal varices and splenomegaly. Urinary concentrating defects and electrolyte imbalances are also common. Some patients may not present until later in childhood or even adolescence, with hepatic complications sometimes predominating. There is currently no cure for ARPKD, and treatment is supportive and symptom-based. Management includes aggressive blood pressure control (often with ACE inhibitors or angiotensin receptor blockers), treatment of respiratory insufficiency in neonates, nutritional support, and management of chronic kidney disease progression. Renal replacement therapy (dialysis or kidney transplantation) may be required for those who progress to end-stage kidney disease. Liver transplantation or combined liver-kidney transplantation may be necessary for patients with severe hepatic fibrosis and portal hypertension. Multidisciplinary care involving nephrologists, hepatologists, and other specialists is essential for optimal outcomes.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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