Genetic kidney disease - Polycystic kidney disease Flashcards Preview

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Flashcards in Genetic kidney disease - Polycystic kidney disease Deck (20)
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What are types of genetic differences that make you more susceptible to a disease?

Family history


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

1. Haploinsufficiency - not enough protein made

2. Gain-of-function - mutant protein causes disease

3. Dominant negative - mutant protein inhibits wild type by interacting with it

4. 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?

1. Cysts accumulate in the kidney and liver at random

2. Grow over course of a person's life

3. High blood pressure develops

4. 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?

1. Control of BP - protect kidney function

2. Avoid dehydration - ADH released from posterior pituitary activates cAMP in cells lining the cysts = causes them to enlarhe

3. Drugs - Tolvaptan blocks V2 receptors and reduces rate of growth of cysts/ progression of kidney failure

4. 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