Genetic Disease Affecting the Kidneys

Question 1

Describe features of APKD

Answer 1

• autosomal dominant inheritance
• mutation in PKD1 or PKD2 gene
• PKD1= more aggressive and ESRD <50y

Question 2

Describe PKD1 and 2 gene mutations

Answer 2

• code for polycystin = membrane proteins involved in intracellular Ca regulation
• located in renal tubular epithelial
• mutation leads to over-expression in cyst cells

Question 3

Describe the clinical presentation of APKD and its consequences

Answer 3

• hypertension
• impaired renal function
• loin pain
• haematuria
• extra-renal manifestations: brain- intracranial aneurysm, cardiac - valvular abnormalities, lung- bronchiectasis, GI - diverticular disease)

consequences: cyst rupture and infection, pain

Question 4

How is a diagnosis of APKD made?

Answer 4

• family history
• US (15-30y: 2 unilateral/bilateral cysts, 30-59y: 2 cysts in each kidney, >60y: 4 cysts in each kidney, no family history: 10+ cysts in both kidneys, renal enlargement, liver cysts)

Question 5

What is the management of APKD?

Answer 5

• supportive
• management of BP
• treatment of complications and extra-renal associations
• prepare for renal replacement therapy

Question 6

What is tolvaptan?

Answer 6

• vasopressin V2 receptor antagonist
• delays onset of need for RRT (4-5y) in APKD
• good for high risk patients (mayo class 1C-E)
• monitoring of LFTs for 18m required

disadvantages:
- hepatotoxicity
- hypernatraemia
- high rate of discontinuation
- expensive

Question 7

Describe Alport’s syndrome

Answer 7

• inherited progressive glomerular disease (X-lined)
• caused by inherited defect in type IV collagen (found in ears, eyes and kidney) - found in BM
• results in deafness and renal failure

Question 8

What changes to the glomerulus occur in Alport’s syndrome?

Answer 8

• mechanical strain
• inflammation
• fibrosis
• degradation of GBM

Question 9

Describe the clinical presentation of Alport’s syndrome

Answer 9

Renal presentation:
- asymptomatic, persistent non-visible haematuria
- proteinuria, hypertension and progressive renal impairment
- ESRD

• sensorineural hearing loss late childhood

Occular defects:
- lens: anterior lenticonus
- retina: bilateral white/yellow granulations
- cornea: posterior polymorphous dystrophy, recurrent corneal erosion

Question 10

What is the treatment of Alport’s syndrome?

Answer 10

• supportive
• BP control

Question 11

Describe Fabry disease

Answer 11

• X-linked lysosomal storage disorder
• results in alpha galactosidase A deficiency causing accumulation of Gb3 in glomeruli, particularly podocytes
• causes proteinuria and ESRF
• also, neuropathy, cardiac and skin features

Question 12

When should you be clinically suspicious of Fabry disease?

Answer 12

• intermittent episodes of burning pain in extremities
• cutaneous vascular lesions (angiokeratomas)
• diminished perspiration
• characteristic corneal and lenticular opacities
• abdo pain, nausea and/or diarrhoea of unknown origin
• LVH/ arrhythmia/ stroke/ CKD and/or proteinuria of unknown cause

Question 13

How is Fabry disease diagnosed and treated?

Answer 13

• measure alpha-Gal A activity in leukocytes
• renal biopsy to look for inclusion bodies of G3b
• treatment: enzyme replacement therapy to inhibit progression of disease and irreversible damage