Genetic Diseases Affecting the Kidneys

Question 1

What is the pathophysiology of APKD?

Answer 1

• AD condition
• PKD 1 and 2 mutations (PKD 1 more common, code for polycystin 1 and 2, polycystins are located in renal tubular epithelia, overexpressed in cyts cells, membrane proteins involved in intracellular calcium regulation)
• Cysts gradually enlarge, kidney volume increases and eGFR falls

Question 2

How is APKD diagnosed?

Answer 2

• Ultrasound
• If FHx US at 21yrs (if negative repeat at 30yrs, age 15-30yrs 2 unilateral or bilateral cysts, 30-59yrs 2 in each kidney, ≥60yrs 4 in each kidney)
• If no FHx 10 or more cysts in both kidneys, renal enlargement, liver cysts
• CT and MRI more sensitive

Question 3

How is APKD managed?

Answer 3

• Supporive
• Early detection and BP management
• Treat complications
• RRT
• Tolvaptan (vasopressin V2 receptor antagonist) can help preserve renal function slightly longer

Question 4

What are the clinical features of Von Hippel Lindau?

Answer 4

• AD condition causing multiple benign and malignant lesions
• Renal cysts and multifocal RCCs in 80%
• Can cause other unusual tumours (e.g. phaeochromocytoma, clear cell carcinoma of CNS)

Question 5

What are the clinical features of tuberous sclerosis?

Answer 5

• AD
• Benign hamartomas of multiple systems (brain, eyes, heart, lungs, liver, kidney and skin)
• Multiple renal cysts, renal angiomyolipomas and RCC

Question 6

What are the clinical features of medullary cystic kidney disease?

Answer 6

• AD
• Cysts at the cortics-medullary junction
• Small to normal sized kidneys
• Hyperuricaemia and gout

Question 7

What are the clinical features of Alport’s syndrome?

Answer 7

• Usually X-linked
• Collagen 4 abnormalities (alpha 3, 4 or 5 gene mutation)
• Deafness and renal failure
• Collagen 4 found in basement membrane
• Consequences include microscopic haematuria, proteinuria, ESRF and sensorineural hearing loss in late childhood

Question 8

What are the clinical features of Fabry’s disease?

Answer 8

• X-linked storage disorder
• Alpha galactosidase A deficiency resulting in accumulation of globotriaosylceramide (Gb3)
• Gb3 accumulates in glomeruli, particularly podocytes causing proteinuria and ESRF
• Also causes nephropathy, cardiac and skin features (angiokeratoma)
• Diagnosed by measuring alpha-Gal A activity in leukocytes and renal biopsy to look for inclusion bodies of Gb3
• Managed with enzyme replacement