Autosomal Recessive Polycystic Kidney Disease

Excerpt

Autosomal recessive polycystic kidney disease is a rare genetic disorder primarily affecting the kidneys and liver. Clinicians should recognize early signs such as enlarged, echogenic kidneys in utero or during infancy. ARPKD most commonly results from mutations in PKHD1, causing renal cysts and congenital hepatic fibrosis early in life. About half of the patients with ARPKD develop end-stage renal failure requiring renal replacement therapy (dialysis or kidney transplantation) within the first 2 decades of life. In addition, hepatic function must be closely followed, as portal hypertension, splenomegaly, and cholangitis are common, especially in older patients.

The 2 varieties of polycystic kidney disease (PKD) based on inheritance are the relatively common autosomal dominant and the much rarer autosomal recessive types. These 2 forms have distinct clinical and genetic features.

Autosomal dominant polycystic kidney disease (ADPKD), previously called adult polycystic kidney disease, is a multisystem progressive cystic disorder primarily affecting the kidneys. It is characterized by bilateral renal cysts, which progressively lead to fibrosis, architectural distortion, hypertension, and progressive renal failure, typically becoming symptomatic starting at about 30 years of age. In adult patients, it is the most frequent genetic cause of renal failure and end-stage kidney disease. Please see the companion StatPearls reference, "Autosomal Dominant Polycystic Kidney Disease," for further information.

Autosomal recessive polycystic kidney disease (ARPKD) primarily involves the kidney and liver. Historically referred to as infantile polycystic kidney disease, it can present in neonatal, infantile, juvenile, or even adult populations. Hence, the old nomenclature of adult and infantile polycystic kidney disease is not used anymore.

ARPKD is characterized by renal distal tubule and collecting duct cyst formation, hepatic biliary duct ectasia/malformation, and fibrosis involving both the liver and kidneys.

ARPKD is a ciliopathy and presents with cysts along the distal renal tubules and collecting ducts, compared to ADPKD, where the cysts can develop anywhere along the nephron. Cysts in ARPKD are mostly microcystic in early childhood, may develop calcifications, and can produce renal calculi. In older children, the cysts become larger and concentrated in the renal medulla.

The clinical presentation of ARPKD varies significantly, with some patients diagnosed at a young age having more severe symptoms than those diagnosed when older. ARPKD is always associated with liver bile duct malformations, both intrahepatic and extrahepatic. Liver manifestations vary from mild cholestasis to hepatic fibrosis, portal vein hypertension, esophageal varices, cholangitis, and cirrhosis.

A key factor in understanding the presentations of ARPKD is that 30% to 40% of affected neonates have been reported to die perinatally, usually due to respiratory distress from pulmonary hypoplasia from oligohydramnios related to decreased fetal urine production. Improved neonatal care has reduced the newborn mortality rate to just 20%.

Survival rates are 85% and 82% for those who survive the perinatal period at 1 and 10 years, respectively. Of note, some of the perinatal data may have been derived from older studies conducted prior to technical advances in neonatal intensive care, reducing perinatal mortality to about 20% within the first month of life.