Autosomal Dominant Polycystic Kidney Disease

Most frequent life-threatening hereditary kidney disease

Aetiology

  • Mutations on PKD gene1 in 85% of cases - located on chromosome 16
  • PKD2 mutations seen in 15% of cases - located on chromosome 4
  • Mutation type has prognostic indications - PKD1 patients develop end stage kidney failure at an earlier stage

Pathophysiology

  • Large cysts form over time because of abnormal proliferation of tubular cells and an increase in cellular secretion with changes in the extracellular matrix
  • Cysts often lined by simple epithelium
  • Often secondary changes - haemorrhage, infarction, rupture

Clinical presentation

Renal

  • Reduced urine concentration ability
  • Chronic pain
  • Hypertension - common, early (mean age 31 years)
  • Haematuria - cyst rupture, cystitis, stones
  • Cyst infection
  • Renal failure

Extra renal

Hepatic cysts
  • Most common extra renal manifestation
  • Liver cysts present 10 years after renal cysts
  • Liver function generally preserved
  • Can result in SOB, pain, ankle swelling
Intra-cranial aneurysms
  • Seen in clusters of family members
  • Mainly in the anterior circulation territory
  • Screening indicated in patients with family history
Cardiac disease
  • Mitral/aortic valve prolapse
  • Valvular disease - collagenous/myxomatous degeneration
Other
  • Diverticular disease - increased incidence and complications
  • Hernias - increased incidence of abdominal/inguinal hernias

ADPKD in children

  • Early onset can be in utero or in first year of life
  • Distinguishing from ARPKD difficult - USS suggestion of congenital hepatic fibrosis suggests recessive disease

Investigations

  • USS - presence of multiple bilateral cyst, renal enlargement
  • MRI (preferred) or CT when unclear on USS
  • Genetic - linkage analysis, mutation analysis

Management

  • Rigorous control of hypertension
  • Education - importance of hydration
  • Proteinurea reduction through blood pressure control
  • Management of cyst haemorrahage and cyst infection
  • New treatment, Tolvaptan (ADH receptor antagonist) is the first drug show to slow loss of kidney function in patients with PKD
  • Genetic counselling - offspring of an affected individual are at a 50% risk of having the disease
  • Management of renal failure - dialysis, transplantation, management of cardiovascular and cerebrovascular factors