Disclaimer:

• Note that polycystic kidney disease can be either inherited or acquired, but most cases are inherited. Therefore, this article will only cover the scope of inherited polycystic kidney disease
• Although this article covers both autosomal dominant and autosomal recessive polycystic kidney disease, greater emphasis is placed on the autosomal dominant form, as it is far more common, clinically relevant, and high yield for exams.
• The diagnosis and management section only focuses on ADPKD

Definition

Inherited polycystic kidney disease is characterised by the development of numerous fluid-filled cysts in the kidneys, and frequently involving manifestation in other organs.

Types and Aetiology

There are 2 main types of inherited polycystic kidney disease

Types	%	Implicated gene
Autosomal dominant	>90%	PKD1 gene (polycystin-1) on chromosome 16 – 85% PDK2 gene (polycystin-2) on chromosome 4 ~20% of the autosomal dominant form are de novo (i.e. no family history)
Autosomal recessive	<10%	PKHD1 gene (fibrocystin) on chromosome 6

Epidemiology

ADPKD is the most common inherited cause of CKD

ADPKD is the 4th most common cause of renal replacement therapy

Clinical Manifestation

Autosomal Dominant Polycystic Kidney Disease (ADPKD)

ADPKD typically occurs in those with a +ve family history (but ~20% of mutations are denovo).

ADPKD is typically adult onset:

• Most common and earliest clinical manifestation: hypertension (often <30 y/o)
• Average age of kidney failure: ~60 y/o (PKD1 mutations generally have more severe disease, and young median age of kidney failure, compared to PDK2 mutation)

Clinical manifestation by organ system:

Organ system	Clinical manifestation
Renal	Hypertension Palpable, enlarged kidneys +/- flank pain (from cyst expansion / mass effect) Haematuria (from cyst rupturing into the collecting system) Low-grade proteinuria (in <20% of patients) Recurrent UTIs ↑ Risk of nephrolithiasis
GI	Hepatic cysts (benign polycystic liver disease, mostly asymptomatic) – most common extra-renal feature Pancreatic cysts Colonic diverticulosis Abdominal wall hernias are more common
Neurological	Intracranial aneurysm (~13% of patients) – risk of rupture leading to subarachnoid haemorrhage
Cardiovascular	Mitral valve prolapse Pericardial effusion (usually asymptomatic) Left ventricular hypertrophy (often a complication of long-standing hypertension) Cardiomyopathy Thoracic aortic aneurysm (rare ~1.5%)

Autosomal Recessive Polycystic Kidney Disease (ARPKD)

Symptom onset occurs most commonly in utero or during infancy ^[Ref1][Ref2]

• ARPKD has high early mortality – ~20-30% of infants die in the 1st year of life (usually due to pulmonary complications)
• Prognosis in those who survived beyond infancy is more favourable (~82% 10-year survival after 1 y/o)

Organ system	Clinical manifestation
Renal	Bilateral renal enlargement Early-onset renal impairment (→ hypertension, CKD, needing renal replacement therapy) Renal impairment in utero can cause oligohydramnios → pulmonary hypoplasia
Extra-renal	Congenital hepatic fibrosis (instead of hepatic cysts in ADPKD) (→ portal hypertension associated complications) Bilateral ductal plate malformation

Investigation and Diagnosis

Diagnostic Work Up

Choice of investigation (for both clinically suspected ADPKD and screening)

• 1st line: abdominal ultrasound
  • Classic findings: multiple bilateral renal cysts of varying sizes + bilateral renal enlargement
  • Diagnostic criteria is based on age-specific cyst counts on ultrasound
• If ultrasound findings are inconclusive: MRI / CT (better detects smaller cysts)

Additional Investigations

Routine renal monitoring (repeat regularly):

• eGFR
• Blood pressure measurement
• Kidney volume measurement (with CT / MRI)

Assessment for extra-renal complications:

Complication of interest	Test of choice	Indications
Polycystic liver disease	Abdominal CT / MRI	ALL patients
Intracranial aneurysm	MR angiography of the head	ANY of the following: Personal history of SAH Family history of intracranial aneurysm / SAH / unexplained sudden death De novo ADPKD Before major elective surgery
Cardiac disease	Echocardiography	ANY of the following: Severe / uncontrolled hypertension Heart murmurs Cardiac symptoms Family history of cardiac disease
Thoracic aortic aneurysm	CT / MR angiography of the chest	ANY of the following: Family history of aortic root 1st degree relative of thoracic aortic aneurysm

Management

ADPKD Management

Mainstay of management is supportive care:

• Optimise and tight blood pressure control (1st line: ACE inhibitor or ARB)
• Limit sodium intake
• Maintain healthy body weight
• Regular physical activity

Tolvaptan is the only recommended pharmacological management to slow disease progression

• MoA: vasopressin 2 receptor antagonist
• Indications: eGFR >25 and at risk of rapid progression
• Regular liver function monitoring is necessary (risk of hepatotoxicity)

Kidney transplantation is the only curative option for patients who developed kidney failure.

Complication Management

Selected points regarding complication management:

• Renal cyst infection
  • 1st line: 4-6 weeks of IV antibiotics (fluoroquinolones or co-trimoxazole)
  • 2nd line: percutaneous / surgical drainage
• Haematuria / cyst haemorrhage → supportive care (it is self-limiting)
• Liver disease
  • Consider somatostatin analogues (e.g. lanreotide, octreotide) if there is marked enlarger liver + severe volume symptoms
  • Consider aspiration sclerotherapy for large dominant cysts
  • Liver cyst infection → IV cephalosporins +/- fluoroquinolones for at least 4 weeks (2nd line: percutaneous drainage)
• Intracranial aneurysm → smoking cessation + strict blood pressure control

References