Flashcards in Genetic Diseases Affecting the Kidneys Deck (26):
Is congenital cystic disease more common in childhood or adulthood?
Rarely presents in childhood
Commonly presents in adulthood
What is a cyst?
Sac like structure containing fluid
In the kidneys these arise from the tubules
What are the complications of a cyst?
Compression of other structures
Replacing useful tissue
Describe the genetics of adult polycystic kidney disease.
Most common inherited kidney disorder
5-10% of patients with end stage renal failure
Either PKD 1 (chr 16) or PKD 2 (chr 4) gene mutation
25% have no known family history
Which gene mutation most commonly causes APKD?
PKD1 - 85%
(PKD2 - 15%)
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
What is the natural history of APKD?
Cysts gradually enlarge
Kidney volume increases
eGFR falls (10yrs before kidneys fail)
How can you diagnose APKD on ultrasound?
Differentiate between simple renal cysts (common in the general population)
- 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
When should someone be given an US for APKD?
- scanned at 21
- again at 30 if negative
What are the clinical consequences of APKD?
- ESRD by 55 (PKD1) or 74 (PKD2)
- berry aneurysm common
Mitral valve prolapse
Colonic diverticular disease
How is APKD managed?
Supportive (no cure)
Early detection and management of blood pressure (delays progression)
Manage extra-renal associations
Renal replacement therapy
- e.g. dialysis
What is Tolvaptan treatment?
Vasopressin V2 receptor antagonist
Helps reduce speed of progression to ESRF
What are the implications of Tolvaptan treatment?
Delays onset of renal replacement therapy by 4-5 years
Very expensive (lifelong drug)
What is Von Hippel Lindau?
Autosomal dominant condition cause multiple benign and malignant neoplasms (not just in the kidneys)
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
What is tuberous sclerosis?
An autosomal dominant genetic condition
Causes benign hamartomas of multiple systems
- kidney (prone to bleeding)
What are the main complications of tuberous sclerosis?
Multiple renal cysts
Renal angiomyolipomas - high risk of bleeding
Renal cell carcinoma
What is medullary cystic kidney disease?
Cyst formation at the cortico-medullary junction (cortex mostly)
What are the complications of medullary cystic disease?
Small to normal sized kidneys
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
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
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
- 12% ESRF by 40years
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
What are the complications associated with Fabry's disease?
ESRF (34 years average)
Neuropathy (fingers and feet)
Cardiac and skin features
How is Fabry's disease diagnosed?
Measurement of alpha-gal A activity in leukocytes
Renal biopsy - inclusion bodies of G3b