Autosomal-dominant polycystic kidney disease (APKD) is estimated to occur in one person per 1,000. A review by Gibson and Watson stresses the importance of early detection of the condition and control of hypertension.
At least two forms of APKD are currently recognized. The more common PKD1 (approximately 86 percent of cases) is attributed to abnormalities on chromosome 16. Patients with PKD1 develop end-stage renal disease at a mean age of 57 (younger in men). PKD2, which is linked to abnormalities on chromosome 4, accounts for fewer than 14 percent of APKD cases. Patients with PKD2 develop end-stage renal disease at an average age of 69. The mechanism of cyst development is not completely understood but involves membrane proteins polycystin 1 and 2, which are important in epithelial-cell differentiation, cell adhesion, ion transport, and cell-to-cell signaling.
Cyst formation often begins in childhood, but APKD may be asymptomatic for many years. Patients may present when cysts distort surrounding tissues (causing pain) or become infected, after hemorrhage into cysts, or when stones form. Diagnosis is usually based on ultrasound scanning.
Approximately 2 percent of PKD1 patients younger than 40 years require renal transplantation, but the proportion rises to 75 percent among those older than 70 years. The rate of progression is variable. Factors that predict a need for early transplantation include male sex, young age at diagnosis, large kidneys, macroscopic hematuria, and hypertension. Blood pressure is the most significant factor in the progression of disease and should be maintained below 130/85 mm Hg. No specific antihypertensive agent is recommended for patients with APKD—the selection should be individualized, based on patient characteristics and response to treatment.
Patients with APKD also may develop abnormalities in other organs. Hepatic cysts may cause hepatomegaly or become infected. Intracranial aneurysms are twice as common in APKD patients than in comparable populations, possibly because of protein abnormalities in arterial walls. These aneurysms rupture at an earlier age than other intracranial vascular abnormalities, often with fatal consequences. Experts disagree on the benefit of screening for occult cranial aneurysms in patients with APKD.