Polycystic kidney disease

Question 1

What is polycystic kidney disease?

Answer 1

Autosomal dominant disorder characterised by development of multiple renal cysts that gradually expand and replace normal kidney substance. Associated with extrarenal (liver and cardiac) abnormalities.

Question 2

What is the aetiology of polycystic kidney disease? (x2)

Answer 2

• Mostly autosomal dominant
• 85% of mutations affect PKD1 (polycystin-1) on chromosome 16, a membrane-bound multidomain protein involved in cell-cell and cell-matrix interactions
• 15% of mutations affect PKD2 on chromosome 4, a Ca2+ permeable cation channel
• There are also recessive types: patients present as neonates

Question 3

What is the pathophysiology of autosomal dominant polycystic kidney disease?

Answer 3

• Proliferative/hyperplastic abnormality of the tubular epithelium
• Initially, cysts are connected to the tubules and contain glomerular filtrate
• When cysts exceed 2mm diameter, most detach, and fluid content is instead derived from secretions of the lining epithelium
• With time, cysts cause damage to adjacent nephrons, compress intrarenal vasculature, promote fibrosis and lead to progressive renal impairment
• Note that although all renal cells will have the mutation, only a minority will develop cysts

Question 4

How does the pathophysiology differ for autosomal recessive PKD?

Answer 4

Cysts arise from collecting ducts rather than tubules and characterised by congenital hepatic fibrosis.

Question 5

What is the epidemiology of PKD: Type? Age of each type?

Answer 5

Dominant much more common than recessive. Dominant present at 3-40 and most have CKD by age 70. Recessive presents with complications in neonates.

Question 6

What are the signs and symptoms of PKD? (x4 +4)

Answer 6

• Pain in flanks as a result of multiple bilateral cyst enlargement/bleeding, stone, blood clot migration or infection
• Haematuria
• Enlarged and cystic kidneys on palpation
• Hypertension from decreased renal function
• Liver palpable from cystic liver (complication of PKD)
• Associated with intracranial ‘berry’ aneurysms which may present as sudden-onset haemorrhage from subarachnoid haemorrhage
• Abdominal hernias or rectus abdominis diastasis (separation of left and right rectus abdominis)
• Signs of associated aortic aneurysm, mitral valve prolapse, or aortic root dilation

Question 7

What are the complications of PKD? (x5) CRUSC

Answer 7

CKD, renal stones, UTI, subarachnoid haemorrhage, cysts in the liver and pancreas

Question 8

What are the investigations for PKD? (x6)

Answer 8

• RENAL USS: multiple, bilateral cysts in enlarged kidneys. May also see liver cysts
• CT/MRI IMAGING: the same as renal USS
• URINALYSIS: assess for renal dysfunction, including haematuria and proteinuria. Can also culture if UTI
• BLOODS: U&Es to assess for CKD
• ECG: in patients suspected of murmurs
• CT BRAIN: in patients suspected of subdural haemorrhage

Question 9

What are the diagnostic criteria for PKD? (x2)

Answer 9

In the presence of FAMILY HISTORY, renal USS must show at least 2 unilateral or bilateral cysts if under 30 years, 2 cysts in each kidney between 30-59, and at least 4 cysts in each kidney for over 59 years. If there is no family history, then diagnosis is by abdominal CT and at least 10 cysts in each kidney. CT can also be performed if there is uncertainty. Photo shows CT.