Congenital Diseases of the Kidney Flashcards
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
How is APKD inherited?
Autosomal dominant
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)
- PKD genes code for the polycystin protein, which is normally:
a. Expressed in kidney tubules, liver and pancreas
b. Involved in intracellular calcium regulation - Overexpression of polycystin causes cyst formation (arising from the kidney tubules)
- 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 Bleeding Pain Infection
How is APKD diagnosed? (2)
Ultrasound
CT/MRI
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
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
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
How would you manage APKD? (5)
Medical treatment:
-Tolvaptan
Supportive treatment:
- Manage BP
- Treat complications
Renal replacement therapy:
- Dialysis
- Kidney transplant
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
How is Von Hippel Lindau inherited?
Autosomal dominant
Describe the pathophysiology of Von Hippel Lindau. (2)
- Causes formation of cysts and multifocal renal cell carcinomas in kidneys
- May cause other rare tumours, e.g.
a. Phaeochromocytoma
b. Haemangioblastoma
c. Clear cell carcinoma (CNS)
How is tuberous sclerosis inherited?
Autosomal dominant
Describe the pathophysiology of tuberous sclerosis. (3)
- Causes benign hamartomas of multiple systems, including the kidneys
- Renal involvement causes multiple cysts, renal angiomyolipomas and renal cell carcinoma
- Also causes CNS involvement, e.g.
a. Epilepsy
b. Learning difficulties
How is medullary cystic kidney disease inherited?
Autosomal dominant
Describe the pathophysiology of medullary cystic kidney disease. (2)
- Formation of cysts at the cortico-medullary junction
2. Associated with hyperuricaemia and gout
How is Alport’s syndrome inherited?
X-linked
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)
SYMPTOMS:
Deafness
Renal failure
Other organs affected, e.g. eyes
CONSEQUENCES: Microscopic haematuria Proteinuria 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?
X-linked
What is Fabry’s disease caused by?
Alpha galactosidase A deficiency
Describe the pathophysiology of Fabry’s disease. (2)
- Alpha Gal A deficiency causes accumulation of Gb3, which accumulates in glomeruli
a. This causes proteinuria and renal failure - This also causes extra-renal symptoms, e.g.
a. Neuropathy
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)
How would you manage Fabry’s disease?
Enzyme replacement therapy
