Genetic Kidney Disease

Question 1

Name some examples of inherited cystic renal diseases

Answer 1

• Von Hippel Lindau,
• Tubular sclerosis
• Autosomal dominant PCKD
• Autosomal recessive PCKD
• Medullary cystic disease

Question 2

What are the different adult polycystic kidney disease mutations?

Answer 2

• PKD 1 (choromosome 16) which is a more common and aggressive mutation.
• PKD 2 (chromosome 4) less common with a slowwer progression, some may never reach ESRD
• Both genes code for polycystin 1 and 2 which are located in renal tubular epithelium (and liver and pancrease), Polycystin is a membrane protein over expressed in cyst cells and it is involved in intracellular calcium regulation

Question 3

Explain the presentation of adult polycystic kideny disease

Answer 3

• Usually presents in the 30-40s.
• It is a multisystem disease which can present with: intracranial aneurysms and arachnoid cysts, hypertension, LVH, valvular abnormalities. Can present with hepatic and pancreatic cysts, bronchiectasis and massively enlarged cystic kidneys which can cause cyst infections/rupture, haematuria, pain and low eGFR

Question 4

Explain the diagnosis of adult polycystic kidney disease

Answer 4

• Detailed family history
• Ultrasound: +family history and 2 cysts (unilateral or bilateral) age 15-30 = diagnoses. 2 If age 30-59 then 2 cysts in each kidney. Age 60+ then 4 cysts in each kidney. If no family history then need 10+ cysts in both kidneys, renal enlargement and liver cysts for diagnosis.
• CT or MRI,
• Genetic testing

Question 5

What is the management for adult polycystic kidney disease?

Answer 5

• Supportive management. Treat hypertension, complications, the extra renal associations and prepare for RRT
• Only medical treatment is Tolvaptan which is an ADH antagonist. This can delay the onset of RRT by 4/5 years. However lots of side effects so high rate of discontinuation.

Question 6

What is Alport’s syndrome?

Answer 6

• An X-linked inherited progressive glomerular disease caused by a defect in type 4 collaged.
• can have mutations in either alpha 3 gene, alpha 4 gene or alpha 5 gene.
• Can present with deafness and renal failure

Question 7

What is the presentation of Alport’s syndrome?

Answer 7

Renal - persistant non visable haematuria from childhoosm proteinuria, hypertension and progressive renal impairment.
Auditory - Hearing loss in late childhoos.
Ocular - anterior lenticonus, bilateral white/yellow granulations in retina and recurrent corneal errosion

Question 8

What is the management of Alport’s syndrome?

Answer 8

BP control

Question 9

What is Fabry disease?

Answer 9

• X linked lysosomal storage disorder caused by alpha galactosidase A deficiency resulting in accumulation of Gb3. Gb3 accumulated in glomeruli causing proteinuria.
• It can also cause neuropathy, cardiac and skin features

Question 10

When should you suspect Fabry Disease?

Answer 10

• Intermittent episodes of burning in extremities,
• Angiokeratomas,
• Diminished perspiration,
• Corneal and lenticular opacities,
• Abdo pain, nausea and/or diarrhoea of unknown cause.
• LVH of unknown aetiology
• Arrhythmias of unknown aetiology
• Stroke of unknown aetiology at any age,
  CKD and proteinuria of unknown aetiology

Question 11

What is the diagnosis and management of Fabry disease

Answer 11

Diagnosis - Measure alpha-Gal A activity in leukocytes (although unreliable in females) or renal biopsy with inclusion bodies of G3b.
Management - Enzyme replacement therapy