Genetic kidney disease - Polycystic kidney disease Flashcards

1
Q

What are types of genetic differences that make you more susceptible to a disease?

A

Family history

Race

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2
Q

What is a characteristic of an autosomal dominant condition?

A

Men and women are affected equally

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3
Q

What is a characteristic of a X linked condition?

A

Affects males in a family

Inherited from mother

No affected offspring with only father affected

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4
Q

What is a characteristic of an autosomal recessive condition?

A

Affected siblings have healthy parents

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5
Q

What are the 4 mechanisms by which an autosomal dominant disease is expressed in the body

A
  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
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6
Q

Describe the process by which somatic second hit leads to condition

A

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

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7
Q

What type of genetic condition is somatic second hit?

A

Inheritance = dominant

Cellularly = recessive, need somatic second hit to be expressed

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8
Q

What conditions are characterised for being somatic second hit?

A

BRCA - ovarian and breast cancer

Polycystic kidney disease

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9
Q

What two genes are linked to polycystic kidney disease?

A

PKD1 and PKD2

Not possible to distinguish in an individual which gene is defective

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10
Q

What percentage of patients with kidney transplants do ADPKD sufferers represent?

A

10% - most common Mendelian condition in the UK

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11
Q

What is the pathophysiology of ADPKD?

A
  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
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12
Q

What is the median age of kidney failure in ADPKD patients?

A

55-65 years

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13
Q

How is ADPKD diagnosed?

A

Family history

Flank pain or blood in urine

Scan for another reason

May present with kidney failure of high BP

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14
Q

What does CT scan of ADPKD sufferers show?

A

Enlarged, cystic architecture of the kidney

Circular, non enhancing, homogenous lesions that surround and abliterate normal parenchyma

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15
Q

What is a nephroctomy?

A

Removal of the kidney

Done in patients with extremely enlarged kidneys

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16
Q

What are the extrarenal manifestations of ADPKD?

A

Increased risk of brain aneurysm

Liver cysts - commonly asymptomatic as don’t cause functional problems

17
Q

What are treatment options for ADPKD sufferers?

A
  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
18
Q

Why do ADPKD sufferers have increased dialysis survival rates compared to sufferers of other renal conditions?

A

ADPKD is mainly a renal condition

Other conditions = multisystemic

19
Q

Why is there a smaller transplant pool amongst ADPKD sufferers?

A

Genetic condition -> family members are likely to have it

20
Q

Treatment for extrarenal manifestations of ADPKD

A

Aneurysms - screening

Liver cysts - rarely need transplant (1%)

Octreotide - agonist for somatostatin receptor, reduces cAMP levels in cyst cells