It is classified into two distinct disorders: autosomal recessive PKD (ARPKD) and autosomal dominant PKD (ADPKD).

Epidemiology

ADPKD: The most common inherited cause of chronic kidney disease

Etiology

• ADPKD
  • PKD1 on chromosome 16 (85% of cases)
  • PKD2 on chromosome 4 (15% of cases)
• ARPKD
  • Mutation in PKHD1 gene on chromosome 6

Pathophysiology

Formation and expansion of cysts in the renal cortex and medulla → compression of renal vessels with activation of the renin-angiotensin-aldosterone system (RAAS), ischemia, and destruction of the kidney parenchyma

Clinical features

ADPKD

• Symptom onset: occur after 30 years of age, but the disease may also manifest during childhood.
  • Cysts develop over many years.
• Renal manifestations
  • Gross hematuria
  • Flank or abdominal pain
    • The pain is often dull and persistent and is thought to be caused by stretching of the wall of a cyst or pressure on other organs when the kidneys and/or liver are very large.
  • Recurrent urinary tract infections
  • Nephrolithiasis
  • Kidneys might be palpable and enlarged on abdominal exam (they are usually normal at birth)
  • Signs of chronic kidney disease (e.g., hypertension, fluid overload, uremia)
• Extrarenal manifestations
  • Multiple benign hepatic cysts (prevalence increases with age)
  • Cysts may also occur in the pancreas, spleen, ovary, and testicles.
  • Cerebral berry aneurysm (∼8%)
    • The risk is higher in patients with a family history positive of ADPKD.
    • May rupture and cause subarachnoid hemorrhage (the risk for growth and rupture is the same in patients with ADPKD as in the general population)
• Cardiovascular
  • Signs of arterial hypertension (e.g., morning headaches) through increased renin production
  • Heart valve defects (particularly mitral valve prolapse)
• Colon diverticula (diverticulosis)

ARPKD

• Symptom onset: Symptoms most commonly manifest in infancy or childhood.
• Renal manifestations
  • Protruding abdomen (nontender abdominal mass) due to bilateral renal enlargement and/or hepatomegaly
  • Chronic renal failure: frequently hematuria, proteinuria, and oliguria
  • Severe in-utero renal impairment → oliguria in utero → maternal oligohydramnios → Potter sequence
• Extrarenal manifestation
  • Hypertension
    • Possibly related to the activation of RAAS and enhanced sodium retention.
  • Liver involvement: congenital hepatic and portal fibrosis → progressive liver failure and portal hypertension

Diagnostics

• ADPKD
  • In adults: enlarged kidneys with multiple cysts bilaterally of varying sizes (anechoic masses)
• ARPKD
  • Enlarged kidneys with multiple cysts bilaterally of equal size

Treatment