Congenital Diseases of the Kidney Flashcards Preview

14. Nephrology and Urology > Congenital Diseases of the Kidney > Flashcards

Flashcards in Congenital Diseases of the Kidney Deck (26)
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1

What are the 6 main types of genetic kidney disease?

CYSTIC DISEASE:
Adult polycystic kidney disease (APKD)
Von Hippel Lindau
Tuberous sclerosis
Medullary cystic kidney disease

NON-CYSTIC DISEASE:
Alport's syndrome
Fabry's syndrome

2

How is APKD inherited?

Autosomal dominant

3

What is APKD caused by? (2)

Which chromosomes are these mutations found on?

PKD1 gene mutation (chromosome 16)
PKD2 gene mutation (chromosome 4)

4

Describe the pathophysiology of APKD. (3)

1. PKD genes code for the polycystin protein, which is normally:
a. Expressed in kidney tubules, liver and pancreas
b. Involved in intracellular calcium regulation

2. Overexpression of polycystin causes cyst formation (arising from the kidney tubules)

3. Cysts gradually enlarge, causing increased kidney volume
a. Healthy areas can compensate at first, but compensation is limited
b. GFR begins to decrease and kidney failure develops within 10 years

5

List 5 consequences of cyst formation in APKD.

Replacing functioning tissue
Compressing other structures
Bleeding
Pain
Infection

6

How is APKD diagnosed? (2)

Ultrasound
CT/MRI

7

Describe the criteria for APKD diagnosis.

For 15-30 yo:
-2 bilateral or unilateral cysts

For 31-59 yo:
-At least 2 cysts in each kidney

For 60+ yo:
-At least 4 cysts in each kidney

For people with no family history:
-At least 10 cysts in each kidney
-Renal enlargement
-Liver cysts

8

In someone with a positive family history of APKD, when would you do an ultrasound to check their kidneys?

21 yo

If negative, repeat at 30 yo

9

What are the consequences of APKD? (11)

RENAL COMPLICATIONS:
Renal failure
Cyst accidents, e.g.
-Rupture
-Bleeding
-Infection

NON-RENAL COMPLICATIONS:
Hypertension
Intracranial aneurysms
Mitral valve prolapse
Aortic incompetence
Colonic diverticular disease
Liver/pancreas cysts
Hernias

10

How would you manage APKD? (5)

Medical treatment:
-Tolvaptan

Supportive treatment:
-Manage BP
-Treat complications

Renal replacement therapy:
-Dialysis
-Kidney transplant

11

What sort of drug is tolvaptan?

List 1 major advantage.

List 4 disadvantages.

Vasopressin V2 receptor antagonist

ADVANTAGE:
-Slows progression of kidney disease by 4-5 years

DISADVANTAGES:
-Heavy monitoring needed
-Hepatotoxicity
-Hypernatraemia
-Very expensive

12

How is Von Hippel Lindau inherited?

Autosomal dominant

13

Describe the pathophysiology of Von Hippel Lindau. (2)

1. Causes formation of cysts and multifocal renal cell carcinomas in kidneys

2. May cause other rare tumours, e.g.
a. Phaeochromocytoma
b. Haemangioblastoma
c. Clear cell carcinoma (CNS)

14

How is tuberous sclerosis inherited?

Autosomal dominant

15

Describe the pathophysiology of tuberous sclerosis. (3)

1. Causes benign hamartomas of multiple systems, including the kidneys

2. Renal involvement causes multiple cysts, renal angiomyolipomas and renal cell carcinoma

3. Also causes CNS involvement, e.g.
a. Epilepsy
b. Learning difficulties

16

How is medullary cystic kidney disease inherited?

Autosomal dominant

17

Describe the pathophysiology of medullary cystic kidney disease. (2)

1. Formation of cysts at the cortico-medullary junction

2. Associated with hyperuricaemia and gout

18

How is Alport's syndrome inherited?

X-linked

19

What is Alport's syndrome caused by? (3)

Collagen 4 abnormalities, e.g.
-Alpha 3 gene mutation
-Alpha 4 gene mutation
-Alpha 5 gene mutation

20

Describe the clinical features of Alport's syndrome.

What are the symptoms? (3)

What are the clinical consequences? (4)

SYMPTOMS:
Deafness
Renal failure
Other organs affected, e.g. eyes

CONSEQUENCES:
Microscopic haematuria
Proteinuria
End stage renal failure
Sensorineural hearing loss

21

Describe the histology of Alport's syndrome.

Thin basement membrane
Split basement membrane

22

How is Fabry's disease inherited?

X-linked

23

What is Fabry's disease caused by?

Alpha galactosidase A deficiency

24

Describe the pathophysiology of Fabry's disease. (2)

1. Alpha Gal A deficiency causes accumulation of Gb3, which accumulates in glomeruli
a. This causes proteinuria and renal failure

2. This also causes extra-renal symptoms, e.g.
a. Neuropathy
b. Cardiac problems
c. Skin involvement, e.g. angiokeratoma

25

How is Fabry's disease diagnosed? (2)

Urine sample (alpha Gal A activity in leukocytes)

Biopsy (inclusion bodies of Gb3)

26

How would you manage Fabry's disease?

Enzyme replacement therapy