Description

• A group of monogenic disorders that results in renal cyst development
• Autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD)
• ADPKD is one of the most common human genetic disorders.

Epidemiology

• ADPKD is generally late onset with end-stage kidney disease (ESKD) developing in older adults.
• ARPKD is usually present in infants.

Prevalence
As ESKD, ADPKD: 8.7/1 million in the United States; 7/1 million in Europe

Etiology and Pathophysiology

• ADPKD results from PKD1 and PKD2 mutations, which encode for polycystin 1 (PC1) and polycystin 2 (PC2). The disrupted polycystin function results in fluid-filled cysts that progressively increase in size, leading to gross enlargement of the kidney, and distortion of the renal architecture.
• ARPKD secondary to PKHD1 mutations

Genetics

• ADPKD: autosomal dominant inheritance
  • PKD1 on chromosome 16p13.3 (85% of patients) encodes PC1.
  • PKD2 on chromosome 4q21 (15% of patients) encodes PC2.
• ARPKD: autosomal recessive inheritance
  • Gene PKHD1 on chromosome 6p21.1–p12 encodes fibrocystin.

Risk Factors

Family history

General Prevention

Genetic counseling

Commonly Associated Conditions

• ADPKD
  • Cysts in other organs
    • Polycystic liver disease in 58% of young age group to 94% of 45-year-olds
    • Pancreatic (5%); seminal (40%); arachnoid (8%)
  • Vascular manifestations
    • Intracerebral aneurysms in 6% of patients without family history and in 16% with family history
    • Aortic root dilation, dissections
  • Cardiac manifestations:
    • Mitral valve prolapse (25%); left Ventricular Hypertrophy
  • Diverticular disease
• ARPKD: liver involvement: affected in inverse proportion to renal disease; congenital hepatic fibrosis with portal HTN