Polycystic Kidney Disease



  • A group of monogenic disorders that results in renal cyst development
  • The most frequent are two genetically distinct conditions: autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD).
  • ADPKD is one of the most common human genetic disorders.


  • ADPKD is generally late onset.
    • Mean age of end-stage kidney disease (ESKD) 57 to 69 years
    • More progressive disease in men than in women
    • Up to 90% of adults have cysts in the liver.
  • ARPKD usually present in infants.
    • A minority in older children and young adults may manifest as liver disease.
    • Nonobstructive intrahepatic bile dilatation is sometimes seen.
    • Found on all continents and in all races


  • Mean age of ESKD: PKD1 mutation, 54.3 years versus PKD2 mutation, 74 years
  • ARPKD affects 1/20,000 live births; carrier level is 1/70.
  • ADPKD affects 1/400 to 1,000 live births.

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

Etiology and Pathophysiology

    • PKD1 and PKD2 mutations, which encode for polycystin 1 (PC1) and polycystin 2 (PC2), disrupt the function of polycystins on the primary cilium, forming fluid-filled cysts that progressively increase in size, leading to gross enlargement of the kidney, and distortion of the renal architecture.
    • Glomerular hyperfiltration compensates for the progressive loss of healthy glomeruli, and therefore, by the time GFR decline becomes detectable, as much as ½ of the original functional glomeruli are irreversibly lost.
    • The majority of patients with ADPKD ultimately progress to ESKD (1).
    • PKHD1 product fibrocystin is also located in cilia.
  • ADPKD: Cysts arise from only 1% of nephrons:
    • Autosomal dominant pattern of inheritance but a molecularly recessive disease with the 2-hit hypothesis
    • Requires genetic and environmental factors
  • ARPKD: Mutations are scattered throughout the gene with genotype–phenotype correlation.


    • Autosomal dominant inheritance
    • 50% of children of an affected adult are affected.
    • 100% penetrance; genetic imprinting and genetic anticipation are seen as well.
    • Two genes isolated
      • PKD1 on chromosome 16p13.3 (85% of patients) encodes polycystin 1.
      • PKD2 on chromosome 4q21 (15% of patients) encodes polycystin 2.
    • Autosomal recessive inheritance
    • Siblings have a 1:4 chance of being affected; gene PKHD1 on chromosome 6p21.1–p12 encodes fibrocystin.

Risk Factors

A more rapidly progressive clinical course is predicted by onset of ESKD at <55 years, development of stage III CKD at <40 years old, onset of HTN at <18 years, total kidney volume greater than the expected for a given age, or presence of multiple complications (gross hematuria, microalbuminuria) (1).

General Prevention

Genetic counseling

Commonly Associated Conditions

    • 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

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