Genetic disorder defined by the pathological development of fluid-filled cysts throughout the kidneys leading to organ enlargement and chronic kidney disease. The morbidity associated with the most common forms, autosomal dominant PKD (ADPKD) and autosomal recessive PKD (ARPKD), is mostly limited to the kidney and liver and extends from neonates to old age.
Numerous polycystic kidney disease classifications have been described (see Table P-1).
TABLE P-1Classification of Polycystic Kidney Disease ||Download (.pdf) TABLE P-1 Classification of Polycystic Kidney Disease
|Type ||Inheritance ||Symptoms |
|Autosomal Recessive Polycystic Kidney Disease (ARPKD) ||Autosomal recessive ||Neonatal or infantile enlarged polycystic kidneys are affected bilaterally; cysts 1-2 mm on average; pulmonary hypoplasia; oligohydramnios; biliary duct anomalies; portal hypertension; cholangitis; congenital hepatic fibrosis on autopsy |
|Autosomal Dominant Polycystic Kidney Disease (ADPKD) ||Autosomal dominant ||Middle-aged to older adults; progressive renal failure as the cysts become larger; rarely seen prenatally or in children; patients are prone to have berry aneurysms of the cerebral arteries |
|Pleiotropic Polycystic Kidney Disease ||Syndromic || |
☞Orofacial Digital Syndrome (OFDS)
Highly variable estimates. 1:400 to 1:20,000 live births overall. The age distribution of cases has two peaks, one at birth and one between the ages of 30 and 60 years.
Autosomal dominant polycytic kidney disease (ADPCK) is caused by mutations in two genes: PKD1 (accounts for 80-85% of patients) and PKD2 (accounts for 15-20%). ARPKD is a neonatal disease caused by mutation in one gene: PKHD1 on chromosome 6p21. Both sexes are affected. Syndromic PKD are caused by a variety of mutations.
Polycystin-1 interacts with polycystin-2, which is a nonselective calcium-permeable channel. Both, polycystin-1 and 2 localize to primary cilia, which trigger intracellular calcium transients upon mechanical stimulation or ligand binding. The PKHD1 gene encodes for fibrocystin and has been localized in primary cilia, as well as to the basal body. It may mediate its activity through polycystin-2. The mutations in PKD1 and PKD2 lead to dysfunction of polycystin-1 and 2 resulting in aberrant cellular signaling pathways with increased or disorganized cell growth and fluid secretion that results in fluid accumulation and cyst formation.
Ultrasonography is the best diagnostic tool, and in late pregnancy can allow presumptive in utero diagnosis in most cases (increased echogenicity and renal enlargement). The feasibility and reliability of DNA obtained by amniocentesis or chorionic villus sampling during prenatal testing is being examined. Hepatic involvement is invariable with generalized portal and interlobular fibrosis, and bile duct proliferation. The remainder of the hepatic parenchyma is normal.