Polycystic Kidney Disease



Polycystic kidney disease (PKD) is a heritable disorder with diffuse cystic involvement of both kidneys without other dysplastic elements. The term PKD is generally used to describe two genetically distinct syndromes:

  • Autosomal dominant polycystic kidney disease (ADPKD)
    • Saccular, epithelial-lined, fluid-filled cysts of various sizes are derived from all segments of the nephron.
    • Cysts progressively enlarge and become disconnected from the tubule of origin.
    • Usually not clinically apparent until the 3rd or 4th decade of life
    • ~2–5% of patients have early-onset disease.
  • Autosomal recessive polycystic kidney disease (ARPKD)
    • Fusiform dilations arise from the collecting ducts and maintain contact with the nephron of origin.
    • Associated hepatic abnormalities include biliary dysgenesis, periportal fibrosis (congenital hepatic fibrosis), and portal hypertension. At the histologic level, almost all patients with ARPKD demonstrate some hepatic fibrosis.
    • Renal abnormalities may progress before liver abnormalities in some patients, whereas, in other patients, liver abnormalities predominate early on before kidney pathology progresses.


    • One of the most common human genetic disorders; the most common renal inherited disease
    • 3rd leading cause of end-stage renal disease (ESRD) in adults (5% of all cases)
    • Frequency: 1 in 400 to 1,000
    • Incidence of 1 in 20,000 to 40,000 live births

Risk Factors


    • Mutations in the polycystic kidney hepatic disease 1 gene (PKHD1, chromosome 6)
    • >300 mutations have been reported in the PKHD1 gene.
    • There is poor correlation between genotype and phenotype.
    • Type I ADPKD accounts for 85–90% of cases of ADPKD and is caused by mutations in the PKD1 gene (chromosome 16).
    • Large genomic deletions may encompass PKD1 and TSC2 genes, resulting in early-onset ADPKD with tuberous sclerosis.
    • Type II ADPKD is caused by mutations in the PKD2 gene (chromosome 4) and accounts for 10–15% of the cases.
  • Nephronophthisis (NPHP) refers to a group of autosomal recessive cystic kidney disease disorders with >20 identified causative genes. NPHP occurs as isolated kidney disease but approximately 15% of NPHP patients also have additional extrarenal symptoms affecting other organs.
  • Other
    • Presymptomatic genetic screening for ADPKD is not recommended.
    • Normotensive women with ADPKD usually have uncomplicated pregnancies.
    • Higher risk for maternal/fetal complications if there is preexisting hypertension


  • Most protein abnormalities that have been associated with cystic kidney disease localize to cilia on epithelial cells.
  • Cilia are critical for cell architecture, proliferation, apoptosis, and polarity.
  • ADPKD is caused by decreased or loss of function of polycystins:
    • Polycystin-1 is a membrane mechanoreceptor-like protein that forms multiprotein complexes at focal adhesions, cell–cell junctions, and cilia. It is involved in cell polarity, proliferation, cell–matrix interactions, and secretion.
    • Polycystin-2 is a divalent cation channel involved in calcium signaling and intracellular calcium homeostasis and is likely critical for cytoskeletal organization, cell adhesion, migration, and proliferation.
  • ARPKD is produced by loss of function of fibrocystin/polyductin:
    • Fibrocystin/polyductin is an integral membrane receptor with extracellular protein-interaction sites that transduce intracellular signals to the nucleus.


  • ADPKD is generally an adult-onset, systemic disorder with cystic and noncystic manifestations. Cyst growth begins in utero but only becomes visible by conventional imaging in adolescence or early adulthood. Cysts occur in the kidneys and other epithelial organs (e.g., seminal vesicles, pancreas, and liver):
    • Polycystic liver disease is the most common extrarenal manifestation occurring in ~90% of patients.
    • Intracranial aneurysms occur in 5–10%.
    • Mitral valve prolapse is the most common valvular abnormality (demonstrated in up to 25% of affected individuals).
    • Colonic diverticula in 80% with ESRD
  • ARPKD is a renal and hepatic developmental disorder. The hallmark of ARPKD liver disease is congenital hepatic fibrosis and dilation of intrahepatic bile ducts (Caroli disease).
    • Severely affected infants may have the oligohydramnios sequence at birth, and associated pulmonary hypoplasia and respiratory complications convey a high mortality risk.

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