Clinical practice. Autosomal dominant polycystic kidney disease.

Shortly after being elbowed in the flank during a pickup basketball game, a 35-year-old healthy man has severe, colicky abdominal pain followed by gross hematuria. He is hospitalized, and a renal ultrasound scan reveals bilateral polycystic kidneys and liver cysts, previously unknown to the patient. The blood pressure is 160/100 mm Hg. The serum creatinine concentration is 0.9 mg per deciliter (80 μmol per liter). The pain subsides in 2 days with analgesics, rest, and fluids; the gross hematuria resolves in 4 days, although microscopic hematuria persists. How should his case be further evaluated and managed? The Clinical Problem Autosomal dominant polycystic kidney disease is an inherited systemic disorder with major renal manifestations and, in some cases, abnormalities in the liver, the pancreas, the brain, the arterial blood vessels, or a combination of these sites. 1 The disease affects approximately 300,000 to 600,000 Americans of either sex, and without racial predilection. Each child of an affected parent has a 50% chance of inheriting the mutated gene, which is completely penetrant. Autosomal dominant polycystic kidney disease arises as a spontaneous mutation in approximately 5% of cases. However, in about one fourth of newly diagnosed cases, patients report no history of the disease, indicating that many familial cases go undetected. Affected patients have numerous fluid-filled cysts in the kidneys; these cysts may collect blood after mild or severe trauma or may be the site of pyogenic infection. In rare cases, a malignant neoplasm develops, although the incidence of renal cancer among affected patients is not increased, as compared with the incidence in the general population. Autosomal dominant polycystic kidney disease begins in utero, but signs of the disease may not be detected for several decades. Autosomal dominant polycystic kidney disease is caused by mutations in either of the two genes encoding plasma membrane–spanning polycystin 1 and polycystin 2 (PKD1 and PKD2, respectively). The polycystins regulate tubular and vascular development in the kidneys and other organs (liver, brain, heart, and pancreas) 2 and interact to increase the flow of calcium through a cation channel formed in plasma membranes by polycystin 2. A mutation of either polycystin can disrupt the function of the other, resulting in similar clinical presentations. However, mutations of PKD1 are more common than mutations of PKD2 (accounting for 85% of cases), are likely to be associated with more renal cysts, 3,4 and lead to renal insufficiency on average 20 years earlier (median ages at the time of death or end-stage failure, 53 and 69 years, respectively). 5