Pathophysiology of Polycystic Kidney Disease

In my continuing quest to understand the actual "why" and "how" behind all pediatric conditions, today I will be working on one of the cystic dysplasias of the kidney - autosomal recessive polycystic kidney disease (ARPKD). This condition results from a mutation in the PKHD1 gene at chromosomal locus 6p12.2. This gene's product, fibrocystin, is found in kidney, liver, and pancreas (this helps you remember the organs involved in ARPKD)

As a reminder, autosomal dominant polycystic kidney disease (ADPKD) is the ADULT type (see what I did there?)

As the name suggests, ARPKD is characterized by the presence of many cysts throughout the kidney's medulla and cortex. These cysts are, in fact, dilated collecting ducts. There is always bilateral involvement and the kidneys are often so enlarged in utero that the abdominal distension may even impede birth! Along with cystic formation, there is often tubular fibrosis which eventually leads to renal failure.

The presentation of ARPKD is most clearly understood when the pathophysiology is understood. When there is a defect in fibrocystin there will be cysts in the kidney, liver, and pancreas. The number of manifestations seen will depend on how quickly the disease progresses. The variable clinical progression hints at the possibility of other genetic or environmental factors.

If renal failure devlops in utero, there will be reduced urine output by the fetus, leading to oligohydramnios. Less amniotic fluid provides minimal padding around the fetus, and the resulting compression causes physical deformities including club foot and flat facies. Also, since amniotic fluid is necessary for pulmonary development, oligohydramnios leads to pulmonary hypoplasia. This constellation of findings - club floot, flat facies, and pulmonary hypoplasia - is called Potter sequence. Lung development may even be further impeded due to compression from the larger kidneys in the abdomen. These infants usually die within days of birth because of the pulmonary hypoplasia.

Hepatic involvement is similar, and is often the major feature in children whose disease did not progress to early death as outlined above. There are multiple cysts. Hepatic fibrosis develops with time. The ensuing portal hypertension leads to another set of presentation findings. Portal hypertension leads to an adaptive development of collateral vessels that aim at decompressing the liver. There will be a resulting increased venous formation at sites where the portal circulation meets the systemic circulation, mainly :

• at the junction of mesenteric and rectal veins, which accounts for hemorrhoid formation.
• at the junction of the umbilical and superficial epigastric vein around the umbilicus, explaining the formation of caput medusae
• in the gastro-esophageal cardial area, which results in esophageal varices. These engorged vessels are fragile and prone to bleeding with often fatal consequences.

The treatment is supportive and the prognosis is poor. Renal and liver transplantation may be beneficial.