Polycystic kidney disease

Question 1

Define polycystic kidney disease. What are the two types?

Answer 1

Inherited renal cystic disease with numerous systemic and extrarenal manifestations.

There are 2 types:

• autosomal-dominant PKD (ADPKD) - MORE COMMON
• autosomal-recessive PKD (ARPKD).

Question 2

What is PKD characterised by?

Answer 2

• Renal cysts
• Extrarenal cysts
• Intracranial aneurysms
• Dolichoectasias (elongated and distended arteries)
• Aortic root dilation and aneurysms
• Mitral valve prolapse
• Abdominal wall hernias

Question 3

How common is PKD? Who is most affected?

Answer 3

• 1 in 1000 Caucasians
• Autosomal dominant is the more common form

Question 4

What are the causes of PKD?

Answer 4

ADPKD:

Two genes have been identified in autosomal dominant PKD:

1. PKD1 - 85% of cases - encodes polycystin 1
2. PKD2 - 15% of cases - encodes polycystin 2

Loss of polycystin function leads to clonal cyst development.

Mean age of onset of ESRD(end-stage renal disease) is 54 years with a PKD1 mutation and 74 years with PKD2

ARPKD:

Often presents in neonates with enlarged echogenic kidneys–> high mortality rate in the first year of life, with many requiring ventilation. 15yr survival is 50-80%.

Question 5

What is the pathophysiology of PKD?

Answer 5

Renal cysts develop and grow over time causing compression of normal renal architecture, vasculature, increasing renal size, interstitial fibrosis and tubular atrophy –> progressive renal impairment.

Question 6

What are the signs and symptoms of polycystic kidney disease?

Answer 6

Palpable kidneys/abdominal mass, renal cysts - multiple bilateral cysts (>10 per kidney) prompt presumptive diagnosis. Hepatomegaly - suggests ADPKD.

Abdominal hernia or rectus abdominis diastasis - often present before renal disease is detected

Hypertension - at young age, presents before renal abnormalities.

Abdominal/flank pain - common; may indicate infection, nephrolithiasis or haemorrhage.

Haematuria, dysuria, urgency, suprapubic pain, fever - 50% to 75% of all patients will experience at least 1 clinical UTI, with the majority occurring in women.

Headaches - may indicate cerebrovascular event

Cardiac murmur - mitral valve prolapse, mitral regurgitation, aortic regurgitation, and dilated aortic root are the most common

Question 7

What investigations would you do for PKD?

Answer 7

Conservative:

Urinalysis/gram stain and urine culture - haematuria, positive culture in UTI.

Serum electrolytes, urea, creatinine- deranged U&E, estimate GFR, follow electrolytes if taking ACEi,

Imaging:

Renal USS - diagnostic criteria in those with +ve FH:

• <30 years of age: at least 2 cysts, unilateral or bilateral
• 30 to 59 years of age: 2 cysts in each kidney;
• >60 years of age: 4 cysts in each kidney

MRI angiography of brain - associated with berry aneurysm in the circle of Willis.

Echocardiogram/ECG - mitral valve prolapse, aortic root dilation, diastolic dysfunction, or LVH in setting of cardiovascular complications

Question 8

What is the prognosis with PKD?

Answer 8

Mean age of onset of ESRD(end-stage renal disease) is 54 years with a PKD1 mutation and 74 years with PKD2

Question 9

What screening is available for PKD?

Answer 9

If +ve family history then ultrasound

Question 10

What is the management of polycystic kidney disease?

Answer 10

• Tolvaptan (vasopressin receptor 2 antagonist) - recommended by NICE for ADPKD to slow cyst progression and renal disease
• Antihypertensives - ACEi or ARBs. CCBs should not be considered. Add BB for those with aneurysms or CVD.

Surgical

• Cyst aspiration under CT guidance - for pain management only
• Dialysis
• Renal transplant

Question 11

What are the complications of PKD?

Answer 11

Cardiac complications e.g. LVH unknown cause

GORD from hepatomegaly - treat with H2 antagonists and PPI

Ruptured intracranial aneurysm - suspect in severe headaches in ADPKD

Sepsis

UTI - more common in advanced disease

Nephrolithiasis