Flashcards in Congenital Diseases of the Kidney Deck (26)
What are the 6 main types of genetic kidney disease?
Adult polycystic kidney disease (APKD)
Von Hippel Lindau
Medullary cystic kidney disease
How is APKD inherited?
What is APKD caused by? (2)
Which chromosomes are these mutations found on?
PKD1 gene mutation (chromosome 16)
PKD2 gene mutation (chromosome 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
List 5 consequences of cyst formation in APKD.
Replacing functioning tissue
Compressing other structures
How is APKD diagnosed? (2)
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
In someone with a positive family history of APKD, when would you do an ultrasound to check their kidneys?
If negative, repeat at 30 yo
What are the consequences of APKD? (11)
Cyst accidents, e.g.
Mitral valve prolapse
Colonic diverticular disease
How would you manage APKD? (5)
Renal replacement therapy:
What sort of drug is tolvaptan?
List 1 major advantage.
List 4 disadvantages.
Vasopressin V2 receptor antagonist
-Slows progression of kidney disease by 4-5 years
-Heavy monitoring needed
How is Von Hippel Lindau inherited?
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.
c. Clear cell carcinoma (CNS)
How is tuberous sclerosis inherited?
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.
b. Learning difficulties
How is medullary cystic kidney disease inherited?
Describe the pathophysiology of medullary cystic kidney disease. (2)
1. Formation of cysts at the cortico-medullary junction
2. Associated with hyperuricaemia and gout
How is Alport's syndrome inherited?
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
Describe the clinical features of Alport's syndrome.
What are the symptoms? (3)
What are the clinical consequences? (4)
Other organs affected, e.g. eyes
End stage renal failure
Sensorineural hearing loss
Describe the histology of Alport's syndrome.
Thin basement membrane
Split basement membrane
How is Fabry's disease inherited?
What is Fabry's disease caused by?
Alpha galactosidase A deficiency
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.
b. Cardiac problems
c. Skin involvement, e.g. angiokeratoma
How is Fabry's disease diagnosed? (2)
Urine sample (alpha Gal A activity in leukocytes)
Biopsy (inclusion bodies of Gb3)