Genetic kidney disease - Polycystic kidney disease Flashcards
What are types of genetic differences that make you more susceptible to a disease?
Family history
Race
What is a characteristic of an autosomal dominant condition?
Men and women are affected equally
What is a characteristic of a X linked condition?
Affects males in a family
Inherited from mother
No affected offspring with only father affected
What is a characteristic of an autosomal recessive condition?
Affected siblings have healthy parents
What are the 4 mechanisms by which an autosomal dominant disease is expressed in the body
- Haploinsufficiency - not enough protein made
- Gain-of-function - mutant protein causes disease
- Dominant negative - mutant protein inhibits wild type by interacting with it
- Somatic second hit
Describe the process by which somatic second hit leads to condition
When cell divides, it may experience a mutation as we age
In normal people - asymptomatic, still have one more copy of the healthy gene
If this happens a second time = no more of the protein is encoded. If this is an oncogene => cancer
In patients with only one normal copy of the gene = somatic second hit (mutation when dividing) is catastrophic
What type of genetic condition is somatic second hit?
Inheritance = dominant
Cellularly = recessive, need somatic second hit to be expressed
What conditions are characterised for being somatic second hit?
BRCA - ovarian and breast cancer
Polycystic kidney disease
What two genes are linked to polycystic kidney disease?
PKD1 and PKD2
Not possible to distinguish in an individual which gene is defective
What percentage of patients with kidney transplants do ADPKD sufferers represent?
10% - most common Mendelian condition in the UK
What is the pathophysiology of ADPKD?
- Cysts accumulate in the kidney and liver at random
- Grow over course of a person’s life
- High blood pressure develops
- Renal function gradually deteriorates
What is the median age of kidney failure in ADPKD patients?
55-65 years
How is ADPKD diagnosed?
Family history
Flank pain or blood in urine
Scan for another reason
May present with kidney failure of high BP
What does CT scan of ADPKD sufferers show?
Enlarged, cystic architecture of the kidney
Circular, non enhancing, homogenous lesions that surround and abliterate normal parenchyma
What is a nephroctomy?
Removal of the kidney
Done in patients with extremely enlarged kidneys
What are the extrarenal manifestations of ADPKD?
Increased risk of brain aneurysm
Liver cysts - commonly asymptomatic as don’t cause functional problems
What are treatment options for ADPKD sufferers?
- Control of BP - protect kidney function
- Avoid dehydration - ADH released from posterior pituitary activates cAMP in cells lining the cysts = causes them to enlarhe
- Drugs - Tolvaptan blocks V2 receptors and reduces rate of growth of cysts/ progression of kidney failure
- Treat urine infection - if infection gets into cysts = difficult to treat since blood supply is removed
Why do ADPKD sufferers have increased dialysis survival rates compared to sufferers of other renal conditions?
ADPKD is mainly a renal condition
Other conditions = multisystemic
Why is there a smaller transplant pool amongst ADPKD sufferers?
Genetic condition -> family members are likely to have it
Treatment for extrarenal manifestations of ADPKD
Aneurysms - screening
Liver cysts - rarely need transplant (1%)
Octreotide - agonist for somatostatin receptor, reduces cAMP levels in cyst cells
