QuestionSBA
QuestionChoice
Berry aneurysms are a recognised feature of autosomal dominant polycystic kidney disease (ADPCKD), which is an inherited cause of end-stage renal failure. The palpable bilateral flank masses should raise suspicion of underlying ADPCKD. Berry aneurysms have a propensity to rupture leading to a subarachnoid haemorrhage, presenting with a traditional sudden-onset 'thunderclap' headache and rapid neurological deterioration.
52907
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Subarachnoid haemorrhage
QuestionChoice
An abdominal aortic aneurysm rupture may present with shock due to bleeding and subsequent reduced consciousness. Headache is not a typical component of the presentation and there is no evidence of haemodynamic instability here. Abdominal aortic aneurysms are also more likely in older male patients.
52909
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Abdominal aortic aneurysm rupture
QuestionChoice
An extradural haematoma typically presents after a traumatic head injury with a brief loss of consciousness followed by recovery (lucid interval) and subsequent rapid deterioration in conscious level. It occurs typically due to a blow to the temples and rupture of the middle meningeal branch of the maxillary artery (a branch of the external carotid). There is no history of trauma in this patient and the clinical features of a lucid interval are not present.
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Extradural haematoma
QuestionChoice
A myocardial infarction (MI) typically presents with chest pain, breathlessness or syncope. Patients are typically older with cardiovascular risk factors. Younger patients may present with MIs, especially if there are strong risk factors such as use of cocaine or hereditary hypercholesterolaemia. ADPKD does not typically increase the risk of MI until there is a significant degree of renal impairment. The most likely cause of this presentation is a berry aneurysm rupture.
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Myocardial infarction
QuestionChoice
Meningitis can cause headache and reduced consciousness. However, the natural history in this case is hyperacute, and therefore a haemorrhage is more likely since meningitis tends to have a more insidious onset. There are also no clinical features of infection, such as fever, or other features of meningism, such as neck stiffness. Furthermore, in this case the presence of bilateral flank masses should also raise suspicion of autosomal dominant polycystic kidney disease and the presence of a ruptured berry aneurysm.
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Meningitis
QuestionComment
"Complained of a headache" is underselling SAH pain a little
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Cystic Juice
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# Summary

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the commonest inherited renal disease. It arises due to mutations in the PKD1 and PKD2 genes. PKD1 mutations are more common and tend to cause more severe disease. The disease is characterised by cyst formation both in the kidneys and in other organs, such as the liver, ovaries, spleen, pancreas and seminal vesicles. Patients may be detected on screening if family members are affected, or present with symptoms of loin pain, haematuria or abdominal masses. Patients may also present with complications such as hypertension and renal impairment. Other complications include cyst haemorrhage or infection, renal stones and an increased risk of cerebral berry aneurysms which may rupture, causing subarachnoid haemorrhage. Ultrasound is the first-line diagnostic investigation to identify renal cysts; genetic testing is not usually required but may be considered in some cases (e.g. atypical renal imaging). Management is primarily supportive, including lifestyle changes, regular monitoring and genetic counselling. Tolvaptan is used in some patients with rapidly progressive chronic kidney disease to slow the growth of renal cysts and renal impairment. Renal replacement therapy may be required if patients develop end-stage kidney disease.

# Definition

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is an inherited renal disorder characterised by continuous formation and growth of cysts in the kidneys. This leads to progressive renal impairment due to destruction of nephrons and may cause end-stage kidney disease (ESKD). 

ADPKD also has several extrarenal manifestations, including cyst formation in the liver and other organs and intracranial aneurysms.

# Epidemiology
 
- ADPKD is the most common genetic kidney disorder in adults
- Prevalence is approximately 1:1000
- Men and women are affected equally, and it occurs in patients of all ethnicities
- It is responsible for up to 10% of end-stage renal disease
- Approximately 85% of patients have PKD1 mutations and 15% have PKD2 mutations
- Around 15% of patients with ADPKD have no family history of the condition (for example due to de novo mutations)
 
# Aetiology

- The PKD genes cause mutations in polycystin 1 and 2, which lead to cyst formation and expansion
- PKD1 is located on chromosome 16, and PKD2 is located on chromosome 4
- Disease is typically more severe with PKD1 mutations
- A large number of causative mutations have been identified
- Inheritance is autosomal dominant

# Signs and Symptoms
 
Patients may present with symptoms of:
 
- Flank pain 
    - May be acute, secondary to cyst haemorrhage, infection or urinary tract stones
    - Chronic pain is common and may be severe
- Haematuria (often due to cyst rupture)
- Fever and systemic illness due to infection i.e. malaise, nausea and vomiting
    - May present with recurrent urinary tract infections
- Polyuria and nocturia
- Chronic kidney disease e.g. lethargy, peripheral oedema, pruritus

Examination findings include:

- Bilateral large masses in the flanks (palpable enlarged kidneys)
- Hepatomegaly (up to 70% have liver cysts)
- Hypertension
- Splenomegaly is rarer (5% have splenic cysts)

# Differential Diagnosis

- **Simple renal cysts** are very common and incidence increases with age
    - Patients have normal sized kidneys and renal function is not affected
    - Symptoms are rare
    - They are often an incidental finding on imaging or autopsy
- **Acquired cystic kidney disease** is common in patients with chronic kidney disease
    - Patients on dialysis are particularly affected
    - Multiple  bilateral small cysts are seen
    - Kidneys are often small in size
    - Cysts are usually asymptomatic
- **Autosomal recessive polycystic kidney disease** is much rarer than ADPKD and manifests in infancy
    - It occurs when two copies of a mutated PKHD1 gene are inherited
    - Patients may be diagnosed in utero and pulmonary hypoplasia may be fatal in neonates
    - Biliary dysgenesis causes cholangitis and portal hypertension
- **Tuberous sclerosis** is an autosomal dominant neurocutaneous disorder that usually occurs due to spontaneous mutations of tumour suppressor genes TSC1 or TSC2
    - Renal cysts are common as well as angiomyolipomas (benign renal tumours)
    - Seizures, learning difficulties and cardiac rhabdomyomas are common features
    - Cutaneous lesions include hypopigmented macules (ash leaf spots), facial angiofibromas (adenoma sebaceum) and shagreen patches
- **Von Hippel-Lindau disease** is a rare autosomal dominant condition that leads to cysts and tumours developing in various organs
    - It is caused by a VHL gene mutation
    - Renal cysts are usually benign and asymptomatic
    - Renal cell carcinoma is more common and patients require surveillance for this
    - Retinal angiomas, haemangioblastomas of the cerebellum or spinal cord, pancreatic neuroendocrine tumours and phaeochromocytomas are other features not seen in ADPKD
- **Medullary cystic kidney disease** is a rare autosomal dominant disease
    - Multiple small medullary cysts are seen
    - Kidneys are small or normal in size
    - Chronic tubulointerstitial nephritis leads to end stage renal disease

# Investigations

**Bedside tests:**

- **Urine dip** for haematuria and proteinuria (microalbuminuria may be seen but heavy proteinuria is rare)
- **Urinary albumin:creatinine ratio** to grade CKD
- **Urine MC&S** if infection is suspected

**Blood tests:**

- **FBC** may show polycythaemia (as polycystic kidneys may produce excessive erythropoietin); leukocytosis may be seen in infection
- **U&Es** to monitor renal function
- **Bone profile** is important in patients with chronic kidney disease to look for electrolyte derangement such as hyperphosphatemia
- **LFTs** are usually normal despite hepatic cysts; rarely large cysts or biliary cystic lesions may cause obstructive jaundice

**Imaging tests:**

- **Ultrasound of the kidneys** is the key diagnostic test and is used for screening adult family members 
    - 3+ renal cysts in total if aged 15-39 is sufficient to diagnose ADPKD
    - 2+ cysts in each kidney if aged 40-59 is sufficient to diagnose ADPKD
    - No cysts if aged 40+ is sufficient to exclude ADPKD
- **CT** or **MRI** of the kidneys is more sensitive and so may be used in specific circumstances e.g. living donor evaluations
- **MRI head** is indicated for screening of patients with a family history of intracranial aneurysms or subarachnoid haemorrhage
- **Abdominal ultrasound** may also detect hepatic or splenic cysts
- **Echocardiogram** if there is suspected valvular disease or hypertensive heart disease

**Special tests:**

- **Genetic testing** is challenging due to the heterogeneity of mutations seen
    - Up to 15% of patients with suspected ADPKD have no identifiable mutation
    - The majority of patients do not require genetic testing
    - It may be useful in atypical cases (e.g. significant asymmetry of cystic disease, no family history) or severe disease
- **Renal biopsy** may be considered in specific cases, for example in patients with nephrotic-range proteinuria to rule out another renal pathology
 
# Management
 
**Conservative management:**

- All patients should be referred to specialist services for diagnosis and management
- Patient education, including providing information regarding implications for family members
- Screening of at-risk adult relatives should be offered - children at risk should have regular blood pressure monitoring
- Advise patients to avoid contact sports which may cause abdominal trauma and cyst rupture
- Lifestyle advice on how to reduce cardiovascular risk should be provided (smoking cessation, healthy diet and regular exercise)
- Avoid nephrotoxic drugs and oestrogens (promote hepatic cyst growth)
- Patients require regular monitoring including serial ultrasounds to monitor renal volume

**Medical management:**

- Tolvaptan is an option for patients with stage 2 or 3 CKD with rapidly progressive disease, to slow cyst growth and renal impairment
- Antihypertensives may be required to maintain a blood pressure of < 130/80
    - ACE inhibitors or angiotensin-II receptor antagonists are first-line
- Analgesia is an important component of pain management, which may be acute or chronic
- Antibiotics may be required for urinary tract infections, including cyst infections

**Surgical management:**

- Drainage of painful or infected renal cysts may be done percutaneously, laparoscopically or via a laparotomy
- Nephrectomy may be required in some cases e.g. very large cysts, uncontrolled haemorrhage, symptomatic mass effect
- For patients with ESRD requiring renal replacement therapy, renal transplant is preferred 
    - Patients often have few comorbidities and so are good candidates
    - In some cases, removal of the native kidney may be required prior to transplantation to make space
    - Rarely, combined liver/kidney transplants are required if there is concurrent severe hepatic cyst disease
- Symptomatic liver cysts may also require drainage or resection
- Intracranial aneurysms detected on screening may be treated prophylactically (e.g. clipping or coiling) - observation is also an option 

# Complications

- **Cyst haemorrhage** and **haematuria** are usually self-limiting
    - Rarely persistent or severe bleeding may cause subcapsular or retroperitoneal haematomas
    - Tranexamic acid may be used to treat bleeding
    - Investigating for malignancy may be appropriate e.g. in older patients or persistent haematuria
- **Cyst infection** usually presents with fever, abdominal pain and raised inflammatory markers
    - Prolonged courses of IV antibiotics may be required
    - Infected cysts may be drained percutaneously or surgically
- **Recurrent urinary tract infections** including pyelonephritis may be seen
- **Renal stones** are common due to increased urinary static and metabolic abnormalities
    - CT is used for diagnosis
    - Treatment is the same as for patients without ADPKD
- **Liver cysts** are the commonest extrarenal manifestation 
    - 80% of patients have liver cysts by the age of 30
    - These increase with age, especially in women
    - 20% of patients will develop symptoms
    - These include abdominal and back pain, abdominal distension, early satiety and gastro-oesophageal reflux
    - Liver cysts may also rupture, bleed or become infected
    - Treatment options include aspiration and sclerotherapy or fenestration of cysts
    - In some cases liver resection is indicated for symptomatic relief
- **Pancreatic cysts** are seen in around 10% of ADPKD patients
    - They usually cause no symptoms
    - If they compress the pancreatic duct, chronic pancreatitis may result
- **Seminal vesicle cysts** are seen in 40% of male ADPKD patients
    - These are usually asymptomatic
    - There is no clear association with infertility
- **Arachnoid membrane cysts** are typically asymptomatic and are found in 8-12% of ADPKD patients
    - However they may increase the risk of subdural haematoma
- **Intracranial aneurysms** may lead to **subarachnoid haemorrhage** if they rupture
    - Decision making around whether to intervene if an unruptured aneurysm is detected is complex
    - Morbidity and mortality from aneurysm rupture are high
    - The majority of aneurysms are in the anterior circulation
- **Aneurysm** may occur elsewhere and lead to arterial dissection
    - The aortic, popliteal, coronary and splenic arteries may be affected
- **Cardiac valvular disease** including mitral valve prolapse and aortic insufficiency with aortic root dilatation
    - These may be progressive but rarely require valve replacement
- **Chronic pain** especially in the flanks is common in ADPKD
    - It may develop after an acutely painful episode
    - Pain may be severe and disabling, with impacts on sleep, activities and mood
    - Treatment involves both medical management with analgesia, and considering interventional options
    - If cyst aspiration relieves pain, more permanent approaches such as cyst scleroisis or fenestration may be considered
- **End stage renal disease** occurs in the majority of patients
    - Renal replacement therapy should be considered early as in all cases of CKD

# Prognosis

- Approximately 50% of patients reach ESRD by the age of 60; this rises to 75% by age 70
- Poor prognostic factors include:
    - PKD1 genotype
    - Younger age of onset
    - Larger kidneys
    - Hypertension
    - Male sex

# NICE Guidelines

[NICE Technology Appraisal - Tolvaptan for treating autosomal dominant polycystic kidney disease](https://www.nice.org.uk/guidance/ta358/)

# References

[KDIGO - Autosomal Dominant Polycystic Kidney Disease](https://kdigo.org/wp-content/uploads/2017/02/KDIGO-ADPKD-Supplemental-Full-Report-FINAL.pdf)

[Patient UK: Polycystic kidney disease](https://patient.info/doctor/autosomal-dominant-polycystic-kidney-disease)

[Genomics Education - Polycystic kidney disease](https://www.genomicseducation.hee.nhs.uk/blog/polycystic-kidney-disease-and-genomic-testing/)

[Radiopaedia - Autosomal dominant polycystic kidney disease](https://radiopaedia.org/articles/autosomal-dominant-polycystic-kidney-disease-1?lang=gb)
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An abdominal CT scan showing multiple renal cysts in someone with polycystic kidney disease.
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ADPKD (Autosomal-Dominant Polycystic Kidney Disease)
Topic
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Nephrology
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Autosomal dominant polycystic kidney disease is associated with berry aneurysms, which can rupture and cause subarachnoid haemorrhage.
A 38-year-old woman is brought in by ambulance to A&E. She was having lunch with a friend when she complained of a headache and lost consciousness soon after. On examination, she has a Glasgow Coma Scale score of 3 and bilateral flank masses palpable on her abdomen. Her observations are otherwise within normal parameters.

What is the cause of her neurological presentation?
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