Polycystic kidney disease

Question 1

Define

Answer 1

• Autosomal dominant inherited disorder characterised by the development of multiple renal cysts that gradually expand and replace normal kidney substance, variably associated with extrarenal (liver and cardiovascular) abnormalities. Can also be autosome recessive (but rare).

Question 2

What mutations are responsible?

Answer 2

• 85% caused by mutations in PKD1 on chromosome 16p12.3
o This is a membrane-bound multidomain protein involved in cell-cell and cell-matrix interactions
• 15% caused by mutations of PKD2 on chromosome 4q21

Question 3

What’s the pathophysiology?

Answer 3

o Proliferative/hyperplastic abnormality of the tubular epithelium
o Early on, the cysts are connected to the tubules from which they arise and the fluid content is glomerular filtrate
o When cyst diameter >2 mm, they detach from the tubule and the fluid content is derived from secretion of the lining epithelium
o With time, the cysts enlarge and cause progressive damage to adjacent functioning nephrons

Question 4

What are the risk factors?

Answer 4

• Family history of ADPKD

- Family history of intracranial aneurysm or SAH

Question 5

Epidemiology

Answer 5

• MOST COMMON inherited kidney disorder
• Responsible for 10% of end-stage renal failure
• By the age of 70, 50% of patients with ADPKD will require dialysis or kidney transplantation

Question 6

What are the presenting symptoms?

Answer 6

• Present at 30-40 yrs
• 20% have no family history
• May be asymptomatic
• Flank Pain - may result from cyst enlargement/bleeding, stone, blood clot migration, infection
• Renal colic
• Haematuria
• Hypertension
• Gross haematuria
• Associated with berry aneurysms and may present with subarachnoid haemorrhage/ headaches
• UTI symptoms
• Family history of intracranial aneurysm/SAH

Question 7

What are the signs?

Answer 7

• Abdominal distension/ hernias
• Enlarged cystic kidneys
• Hepatomegaly
• Hypertension
• Signs of chronic renal failure (at late stage)
• Signs of associated AAA or aortic valve disease (cardiac murmur)

Question 8

What are the appropriate investigations?

Answer 8

US/CT scan
o Will show multiple cysts bilaterally in enlarged kidneys
o Liver cysts may also be seen