Polycystic kidney disease (PKD) is a genetic disorder characterized by the development of multiple renal cysts, leading to progressive kidney enlargement and eventual renal dysfunction. It is an important topic for the UKMLA, emphasizing pathophysiology, clinical features, diagnosis, and management.

Key Types:

1. Autosomal Dominant Polycystic Kidney Disease (ADPKD):

1. • Most common form.
   • Presents in adulthood.
   • Mutations in PKD1 (85% cases) or PKD2 genes.

2. Autosomal Recessive Polycystic Kidney Disease (ARPKD):

1. • Rare and severe.
   • Presents in infancy or early childhood.
   • Mutation in PKHD1 gene.

Key Features:

• Progressive development of bilateral renal cysts.
• Gradual decline in renal function.
• Associated extrarenal manifestations.

Clinical Presentation:

1. ADPKD (Adult Presentation):

1. • Hypertension (early sign).
   • Recurrent flank or abdominal pain.
   • Haematuria (gross or microscopic).
   • Recurrent urinary tract infections (UTIs), often involving cyst infections.
   • Nephrolithiasis (calcium oxalate or uric acid stones).
   • Progressive renal failure (leading to CKD or ESRD).

2. ARPKD (Infant/Child Presentation):

1. • Enlarged, palpable kidneys.
   • Respiratory distress (due to pulmonary hypoplasia in neonates).
   • Hypertension in early childhood.
   • Hepatic fibrosis leading to portal hypertension.

Extrarenal Manifestations:

1. ADPKD:

1. • Liver Cysts: Common but usually asymptomatic.
   • Intracranial Berry Aneurysms: Increased risk of subarachnoid haemorrhage.
   • Mitral Valve Prolapse and other cardiac abnormalities.
   • Diverticulosis: Colonic diverticula.
   • Hernias: Inguinal or abdominal.

2. ARPKD:

1. • Congenital Hepatic Fibrosis: Portal hypertension and oesophageal varices.
   • Biliary Dysgenesis.

Investigations:

1. Imaging Studies:

1. • Ultrasound (first-line):
     • Multiple bilateral renal cysts.
     • Diagnostic criteria for ADPKD based on age and number of cysts.
   • CT/MRI:
     • Detailed evaluation if ultrasound inconclusive.
     • Useful for detecting complications (e.g., cyst infection or rupture).

2. Laboratory Tests:

1. • Renal function tests: Monitor progression (eGFR, creatinine).
   • Urinalysis: Haematuria, proteinuria.
   • Genetic testing: For confirmation in inconclusive cases or family screening.

3. Screening for Extrarenal Manifestations:

1. • MRA/CT Angiography: Screen for intracranial aneurysms in patients with a family history or high-risk occupations.
   • Liver Ultrasound: Assess for liver cysts.

Management:

1. General Measures:

1. • Blood pressure control: Target <130/80 mmHg.
   • Dietary salt restriction.
   • Encourage fluid intake to reduce vasopressin activity.

2. Specific Therapies:

1. • Tolvaptan:
     • Vasopressin receptor antagonist; slows disease progression in ADPKD.
     • Monitor for hepatotoxicity.
   • Antibiotics for Infections:
     • For cyst infection: Fluoroquinolones or trimethoprim-sulfamethoxazole penetrate cysts well.
   • Analgesia:
     • For chronic flank pain; avoid NSAIDs to preserve renal function.

3. Management of Complications:

1. • Hypertension: ACE inhibitors/ARBs are first-line.
   • Hematuria: Bed rest and hydration.
   • Nephrolithiasis: Hydration and stone-specific treatment.
   • ESRD: Dialysis or renal transplantation.

4. Extrarenal Management:

1. • Monitor and manage intracranial aneurysms (surgical clipping or endovascular repair for large aneurysms).
   • Treat hepatic cysts if symptomatic (e.g., drainage, sclerotherapy).

5. ARPKD:

1. • Neonatal intensive care for respiratory distress.
   • Blood pressure control.
   • Liver transplantation for severe hepatic fibrosis.

Screening Recommendations:

1. Family Screening:
   • Ultrasonography in at-risk family members.
   • Genetic testing if available.
2. Pregnancy:
   • Monitor closely; increased risk of preeclampsia.

Complications:

1. Renal:

1. • Chronic Kidney Disease (CKD) and progression to ESRD.
   • Cyst rupture or haemorrhage.
   • Recurrent infections (e.g., pyelonephritis, infected cysts).

2. Cardiovascular:

1. • Intracranial aneurysms (subarachnoid haemorrhage risk).
   • Hypertension-related complications (e.g., left ventricular hypertrophy).

3. Extrarenal:

1. • Hepatic cyst complications (infection, rupture).
   • Diverticulitis or perforation (colonic).

Key Exam Points for UKMLA:

• ADPKD:
  • Hypertension is often the first presenting feature.
  • Diagnostic imaging criteria vary by age group.
  • Tolvaptan slows progression but requires liver function monitoring.
  • Know the association with berry aneurysms and when to screen.
• ARPKD:
  • Presents in neonates or early childhood.
  • Associated with congenital hepatic fibrosis.
• Differentiating PKD from Other Cystic Kidney Diseases:
  • ADPKD vs. simple cysts: Number and bilaterality of cysts.
  • PKD vs. medullary sponge kidney: Medullary cysts and nephrocalcinosis in the latter.