Genetic Diseases Affecting the Kidneys Flashcards Preview

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Flashcards in Genetic Diseases Affecting the Kidneys Deck (26):
1

Is congenital cystic disease more common in childhood or adulthood?

Rarely presents in childhood
Commonly presents in adulthood

2

What is a cyst?

Sac like structure containing fluid
In the kidneys these arise from the tubules

3

What are the complications of a cyst?

Compression of other structures
Replacing useful tissue
Becoming infected
Bleeding
Pain

4

Describe the genetics of adult polycystic kidney disease.

Most common inherited kidney disorder
5-10% of patients with end stage renal failure
Autosomal dominant
Either PKD 1 (chr 16) or PKD 2 (chr 4) gene mutation
25% have no known family history

5

Which gene mutation most commonly causes APKD?

PKD1 - 85%
(PKD2 - 15%)

6

How do PKD1 and 2 gene mutations cause APKD?

The genes code for polycystin 1 and 2
- these are located in the renal tubular epithelia (and liver and pancreas ducts)
- overexpressed in cyst cells
- membrane proteins involved in intracellular calcium regulation

7

What is the natural history of APKD?

Cysts gradually enlarge
Kidney volume increases
Some compensation
eGFR falls (10yrs before kidneys fail)

8

How can you diagnose APKD on ultrasound?

Differentiate between simple renal cysts (common in the general population)
Family history
- age 15-30 - 2 unilateral or bilateral cysts
- age 30-59 - 2 cysts in each kidney
- over 60 - 4 cysts in each kidney
No family history
- 10 or more cysts in both kidneys, renal enlargement and liver cysts

9

When should someone be given an US for APKD?

Symptoms
Family history
- scanned at 21
- again at 30 if negative

10

What are the clinical consequences of APKD?

Renal complications
- ESRD by 55 (PKD1) or 74 (PKD2)
Hypertension
Intracranial aneurysms
- berry aneurysm common
Mitral valve prolapse
Aortic incompetence
Colonic diverticular disease
Liver/pancreas cysts
Hernia

11

How is APKD managed?

Supportive (no cure)
Early detection and management of blood pressure (delays progression)
Treat complications
Manage extra-renal associations
Renal replacement therapy
- e.g. dialysis

12

What is Tolvaptan treatment?

Vasopressin V2 receptor antagonist
Helps reduce speed of progression to ESRF

13

What are the implications of Tolvaptan treatment?

Delays onset of renal replacement therapy by 4-5 years
Heavy monitoring
Side effects
- hepatotoxicity
- hypernatraemia
- dehydration
Very expensive (lifelong drug)

14

What is Von Hippel Lindau?

Autosomal dominant condition cause multiple benign and malignant neoplasms (not just in the kidneys)

15

What neoplasms can Von Hippel Lindau form?

Can cause renal cysts and multifocal renal cell carcinomas
Can also cause phaechromocytoma, haemangioblastoma, clear cell carcinoma of the CNS

16

What is tuberous sclerosis?

An autosomal dominant genetic condition
Causes benign hamartomas of multiple systems
- brain
- eyes
- heart
- lung
- liver
- kidney (prone to bleeding)
- skin

17

What are the main complications of tuberous sclerosis?

Multiple renal cysts
Renal angiomyolipomas - high risk of bleeding
Renal cell carcinoma
Epilepsy
Learning difficulties

18

What is medullary cystic kidney disease?

Autosomal dominant
Cyst formation at the cortico-medullary junction (cortex mostly)

19

What are the complications of medullary cystic disease?

Small to normal sized kidneys
Hyperuriecaemia
Gout

20

What is Alport's syndrome?

X-linked, so normally affects men (but women can be a carrier)
Second most common inherited disease
Collagen 4 abnormalities
- due to alpha 3, 4 or 5 gene mutations

21

What are the complications of Alport's syndrome?

Deafness and renal failure
- affects basement membranes such as cochlear and kidney GBM
- split, thin and laminated GBM
Can also affect the eyes

22

What are the clinical consequences of Alport's syndrome?

Microscopic haematuria, proteinuria and ESRF
- 90% on dialysis by 40 years
Sensorineural hearing loss in late childhood
Carriers
- 12% ESRF by 40years

23

What is Fabry's disease?

X-linked storage disorder
Alpha galactosidase A deficiency resulting in accumulation of globotriaosylceramide (Gb3)
- Gb3 accumulates in glomeruli, particularly podocytes

24

What are the complications associated with Fabry's disease?

Proteinuria
ESRF (34 years average)
Neuropathy (fingers and feet)
Cardiac and skin features
- angiokeratoma

25

How is Fabry's disease diagnosed?

Measurement of alpha-gal A activity in leukocytes
Renal biopsy - inclusion bodies of G3b

26

How is Favry's disease managed?

Enzyme replacement therapy
- early diagnosis needed