Polycystic Kidney Disease (PKD)

Definition | Aetiology | Pathophysiology | Risk Factors | Signs and Symptoms | Investigations | Management

Definition

Polycystic Kidney Disease (PKD) is a genetic disorder characterised by the formation of fluid-filled cysts in the kidneys, leading to progressive renal enlargement and dysfunction.

Aetiology

PKD is classified into two types:

1. Autosomal Dominant PKD (ADPKD) – Most Common:

  • Mutations in PKD1 (85%) or PKD2 (15%) genes.
  • Typically presents in adulthood (third to fifth decade).
  • Progressive kidney cyst formation leads to chronic kidney disease (CKD).

2. Autosomal Recessive PKD (ARPKD) – Rare:

  • Mutation in PKHD1 gene.
  • Typically presents in infancy or early childhood.
  • Associated with congenital hepatic fibrosis and respiratory distress.

Pathophysiology

  • Mutations in PKD genes cause abnormal cell proliferation.
  • Fluid accumulates within cysts, leading to kidney enlargement.
  • Compression of renal parenchyma leads to nephron loss and progressive CKD.
  • Increased renin angiotensin aldosterone system (RAAS) activation contributes to hypertension.

Risk factors

  • Family history of PKD.
  • PKD1 mutation (more severe progression than PKD2).
  • Hypertension.
  • Male sex (tends to have more severe disease).
  • High protein and high sodium diet.
  • Multiple pregnancies (increased cyst growth risk).

Signs and symptoms

PKD symptoms typically appear in adulthood for ADPKD and in infancy for ARPKD.

Common Features:

  • Hypertension: often an early sign.
  • Flank pain: due to cyst expansion or rupture.
  • Haematuria: microscopic or macroscopic.
  • Recurrent urinary tract infections (UTIs): due to cyst infection.
  • Kidney stones: more common in PKD patients.
  • Progressive renal impairment: leading to CKD and eventually end stage renal disease (ESRD).

Extrarenal Manifestations:

  • Hepatic cysts: more common in women.
  • Intracranial aneurysms: increased risk of subarachnoid haemorrhage (SAH).
  • Mitral valve prolapse: associated cardiac abnormality.
  • Diverticulosis: common in PKD patients.

Investigations

  • Renal ultrasound: first line for diagnosis (multiple bilateral cysts confirm ADPKD).
  • CT or MRI abdomen: more sensitive for detecting small cysts.
  • Genetic testing: considered in uncertain cases or family screening.
  • Blood tests:
    • Renal function tests (U&Es, eGFR): monitors kidney function.
    • Serum electrolytes: assess for metabolic disturbances.
  • Urinalysis: haematuria and proteinuria assessment.
  • Blood pressure monitoring: essential for early detection of hypertension.
  • Intracranial imaging (if high risk of aneurysm): MRI brain if family history of SAH.

Management

1. Blood Pressure Control:

  • Target BP: <130/80 mmHg.
  • First line: ACE inhibitors (e.g., Ramipril 5 mg daily) or ARBs.
  • Monitor kidney function: risk of hyperkalaemia with ACE inhibitors.

2. Slowing Disease Progression:

  • Increased water intake: reduces vasopressin levels and cyst growth.
  • Low-sodium diet: helps with BP and cyst progression.
  • Tolvaptan (vasopressin receptor antagonist): considered for rapidly progressing ADPKD.

3. Symptom Management:

  • Pain management: paracetamol preferred; avoid NSAIDs due to nephrotoxicity.
  • Antibiotics for cyst infections: ciprofloxacin or trimethoprim.
  • Management of nephrolithiasis: encourage hydration, consider alkalinisation therapy.

4. Management of Complications:

  • CKD progression: regular monitoring of eGFR.
  • Dialysis (Haemodialysis or Peritoneal Dialysis): if ESRD develops.
  • Renal transplantation: considered in ESRD patients.
  • Intracranial aneurysm screening: MRI brain in high-risk individuals.

5. Lifestyle and Monitoring:

  • Encourage smoking cessation.
  • Weight management and regular exercise.
  • Monitor renal function every 6–12 months.
RenalmypanotesPolycystic Kidney Disease (PKD)