Diagnosis: Autosomal Dominant Polycystic Kidney Disease
• Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common human heritable diseases, affecting approximately 1:500 to 1:1000 individuals. The disease is characterized by bilateral renal cyst formation, leading to massively enlarged kidneys.
• Initial clinical manifestations of ADPKD typically are seen between 20 and 40 years of age and include renal insufficiency, hypertension, hematuria, and renal colic. The disease is slowly progressive, and most patients develop end-stage renal disease. Patients with ADPKD account for 8% to 10% of patients with end-stage renal disease in the United States. Rare cases of ADPKD manifest in infancy or childhood.
• The most common extrarenal manifestation of ADPKD is hepatic cyst, which is seen in 50% of patients. Although polycystic liver disease may cause pain, it is not associated with functional impairment. Other complications of ADPKD reflect the expression of polycystin in vascular smooth muscle. Cardiac valve abnormalities, in particular, mitral valve prolapse, occur in 25% of patients. Intracranial berry aneurysms are the most catastrophic complication of ADPKD, affecting 5% to 8% of patients.
• Mutations in the genes PKD1 (located on chromosome 16) and PKD2 (located on chromosome 4) are responsible for 85% and 13% of cases of ADPKD, respectively. The gene products, polycystin 1 and polycystin 2, are proteins that regulate renal epithelial cell proliferation and differentiation. The mechanism of cyst formation requires an inherited (autosomal dominant) mutation of one allele and the development of a somatic mutation (second hit) in the second allele.
• In ADPKD, the kidneys are markedly enlarged (8 kg and 40 cm in length). The expanded renal parenchyma comprises a massive aggregate of cysts lined by flattened-to-cuboidal epithelium.
