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% |
~20% of the autosomal dominant form are de novo (i.e. no family history) |
| Autosomal recessive | <10% |
|
Epidemiology
ADPKDAutosomal dominant polycystic kidney disease is the most common inherited cause of CKDChronic kidney disease
ADPKDAutosomal dominant polycystic kidney disease 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 |
|
| GI |
|
| Neurological |
|
| Cardiovascular |
|
Note that ADPKD is typically asymptomatic in childhood (as mentioned above, it is typically adult-onset).
Therefore, a child presenting with palpable renal mass (esp. if unilateral) and haematuria is more suggestive of Wilms tumour.
Primary cause of death in ADPKD is cardiovascular disease, often occurring even after a kidney transplant.
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 |
Renal impairment in utero can cause oligohydramnios → pulmonary hypoplasia |
| Extra-renal |
|
It is common for bilateral renal enlargement and hepatic fibrosis in ARPKD to cause abdominal deformity, particularly in infants and young children
Investigation and Diagnosis
The following applies for ADPKD.
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
The number of cysts are expected to increase with age. Diagnostic age-specific cyst coutns:
- 15-39 y/o → ≥3 total cysts (unilateral or bilateral)
- 40-59 y/o → ≥2 cysts in each kidney
- ≥60 y/o → ≥4 cysts in each kidney
- If ultrasound findings are inconclusive: MRI / CT (better detects smaller cysts)
Genetic testing is NOT routinely indicate to diagnose ADPKD.
Genetic testing is indicated in:
- -ve Family history (as ~20% of cases are de novo mutations)
- Equivocal / atypical imaging
- Very-onset ADPKD (symptom onset <18 m/o)
- Family planning
- Prognostic information (PKD1 mutation is worse)
Screening for at-risk adults:
- 1st line: abdominal ultrasound (in adults with an affected 1st-degree relative)
- Genetic screening can be used to definitively diagnose or exclude ADPKD (in families with identified specific pathogenic variant)
Additional Investigations
Routine renal monitoring (repeat regularly):
- eGFR
- Blood pressure measurement
- Kidney volume measurement (with CT / MRI)
The total kidney volume (measured on CT / MRI) is the most important prognostic marker for predicting future key function decline and timing of kidney failure.
Other poor prognostic factors:
- PKD1 mutations (than PKD2 mutation)
- Male
- Early-onset hypertension (<35 y/o)
- Declining eGFR
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:
|
| Cardiac disease | Echocardiography | ANY of the following:
|
| Thoracic aortic aneurysm | CT / MR angiography of the chest | ANY of the following:
|
It would be unnecessary to learn all the exact indications of the extra-renal investigations, key important things to learn:
- Assessment for hepatic cysts is necessary in ALL patients
- Assessment for intracranial aneurysm is one of the most important test (as aneurysm rupture causing SAHSubarachnoid haemorrhage is the most severe extra-renal complication) (but NOT necessary in ALL patients)
Management
The following applies for ADPKD.
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