General Principles

• Autosomal dominant polycystic kidney disease (ADPKD) is a hereditary disorder resulting in cystic enlargement of the kidneys. The incidence is estimated to be 1 in 500 to 1000 live births. Approximately 20% of patients with ADPKD do not have a positive family history. ADPKD currently accounts for up to 10% of patients with ESRD.
• There are two well-described mutations in the polycystin genes, PKD1 and PKD2 which encode for polycystin (PC) 1 and 2, respectively. PKD1 is more common, accounting for approximately 85% of ADPKD. PKD2 is associated with later progression of disease.
• The mechanism by which cysts form is unclear; a proposed “two-hit” hypothesis implicates a second somatic mutation that inactivates the wild-type allele in individual cells. The polycystin gene products localize to the primary cilium of the apical membrane of tubular cells. Disordered cell division and aberrant planar cell polarity may lead to overgrowth of the tubular segment, eventually pinching off from the rest of the collecting system and forming discrete cysts. In abnormal cells, cyclic AMP imparts a proliferative phenotype as well as inducing chloride extrusion into the cyst lumen.