Genetic Disease Affecting the Kidney

Question 1

Give examples of inherited cystic renal disease?

Answer 1

Autosomal dominant polycystic kidney disease
Von Hippel Lindau
Tuberous sclerosis
Autosomal recessive polycystic kidney disease
Medullary cystic disease

Question 2

Describe the outcome of adult polycystic kidney disease with a PKD1 mutation compared to a PKD2 mutation

Answer 2

PKD1 mutations rapidly progress to end stage renal disease

PKD2 mutations have a slower progression and may never reach this stage

Question 3

Genetic testing for ADPKD is routine. T/F?

Answer 3

False - but its use is increasing

Question 4

Describe the various presentations of ADPKD?

Answer 4

Incidental finding on ultrasound
Hypertension
Impaired renal function
Loin pain
Haematuria

Question 5

Describe the pathogenesis of ADPKD?

Answer 5

Genetic disease where mutations in PKD1/2 result in over expression of membrane proteins involved in intracellular calcium regulation in the renal tubular epithelium. This causes cyst formation. Cysts gradually enlarge, normal kidney tissue is placed, kidney volumes increase and eGFR falls

Question 6

What are the possible extra-renal manifestations of ADPKD?

Answer 6

Intracranial aneurysms
Hypertension
Valvular abnormalities
Hepatic and pancreatic cysts
Bronchiectasis
Diverticular disease

Question 7

How is ADPKD diagnosed?

Answer 7

Ultrasound

Question 8

What is the diagnostic criteria for ADPKD ins someone with a family history of the disease?

Answer 8

15-30 years old 2 unilateral/bilateral cysts present
30-59 years old 2 cysts present in each kidney
>60 years old 4 cysts present in each kidney

Question 9

What is the diagnostic criteria for ADPKD ins someone without a family history of the disease?

Answer 9

10 or more cysts present in both kidneys with renal enlargement
Sometimes liver cysts are present also

Question 10

How is ADPKD managed?

Answer 10

Supportively - manage blood pressure, treat complications, manage extra-renal associations, prepare for renal replacement therapy

Question 11

Describe the use of tolvaptan in ADPKD?

Answer 11

Vasopressin V2 receptors antagonist
Requires intensive monitoring of LFTs for 18 months
Side effects include hepatotoxicity and hypernatraemia

Question 12

What type of genetic inheritance is seen in Alpert’s syndrome?

Answer 12

X-linked

Question 13

What is the second most common inherited kidney disease?

Answer 13

Alport’s syndrome

Question 14

In Alpert’s syndrome there are abnormalities in collagen four. What mutations can cause this?

Answer 14

Alpha 3 gene
Alpha 4 gene
Alpha 5 gene

Question 15

What are the symptoms of Alpert’s syndrome?

Answer 15

Deafness
Renal failure
Can affect other organs including eyes

Question 16

What type of genetic inheritance is seen in Fabry’s disease?

Answer 16

X-linked

Question 17

Describe the pathogenesis of Fabry’s disease?

Answer 17

Galactosidase A deficiency, resulting in accumulation of Gb3 in the glomeruli and podocytes causing proteinuria and end stage renal failure

Question 18

What is the average age of onset of Fabry’s disease?

Answer 18

34 years

Question 19

In addition to its affects on the kidneys, what other organs can Fabry’s disease affect?

Answer 19

Heart

Skin

Question 20

How is Fabry’s disease diagnosed?

Answer 20

Measuring Gal A activity in leukocytes
Renal biopsy (showing inclusion bodies of G3b)

Question 21

How is Fabry’s disease managed?

Answer 21

Enzyme replacement therapy