Inherited Kidney Disease

Question 1

What is ADPKD

Answer 1

Autosomal dominant polycystic kidney disease, ~10% have de novo mutation
Mutation in PKD1 (chromosome 16, 85% of cases) reaches ESRF by 50s, PKD2 (chromosome 4) in 70s

Question 2

ADPKD presentation

Answer 2

Clinically silent unless cysts symptomatic due to size/ haemorrhage/ infection
Loin pain
Visible haematuria
Renal calculi
Progressive renal failure
Intracranial aneurysm

Question 3

ADPKD diagnosis

Answer 3

USS 15-39yrs ≥3 cysts, 40-59 >2 cysts in each kidney gives PPV of 100%
Liver and pancreatic cysts support diagnosis
CT for renal colic as cysts obscure USS view
MRI for intracranial aneurysm screening

Question 4

ADPKD treatment

Answer 4

Water intake 3-4L/day (if GFR>30) may suppress cyst growth
BP to target <130/80
Cyst decompression for persistent pain
RRT prep if needed

Question 5

What is ARPKD

Answer 5

Autosomal recessive PKD
Chromosome 6 mutation
No specific therapy

Question 6

ARPKD presentation

Answer 6

Presents ante/perinatally with renal cysts (salt and pepper USS)
Congenital hepatic fibrosis -> portal hypertension
Poor prognosis if neonatal respiratory distress

Question 7

What is Tuberous sclerosis complex

Answer 7

Autosomal dominant multisystem disorder with hamartoma formation in skin, brain (epilepsy), eye, heart and lung
TSC1 (chromosome 9) and TSC2 (chromosome 16) genes
In kidney causes angiomyolipomata (benign kidney tumours) with risk of aneurysm + haemorrhage

Question 8

Tuberous sclerosis complex treatment

Answer 8

mTORC1 inhibitors (sirolimus, everolimus) block pathological signalling and reduce tumour volume

Question 9

What is Von Hippel-Lindau syndrome

Answer 9

Autosomal dominant mutation in VHL gene (chromosome 3) causing uncontrolled growth factor activation
Multisystem cancer syndrome including renal cysts + clear cell renal carcinoma at mean age 40s

Question 10

Von Hippel-Lindau syndrome management

Answer 10

Tumour screening

Question 11

What is Alport syndrome

Answer 11

X-linked COL4A5 gene mutations which encodes alpha-5 chain of type IV collagen

Question 12

Alport syndrome presentation

Answer 12

Haematuria
Proteinuria
Progressive renal insufficiency
Average age of renal failure 30-40yrs in men, women can exhibit phenotype at average age 60

High-tone sensorineural hearing loss
Bulging of lens on slit-lamp examination

Question 13

Alport syndrome transplant difficulties

Answer 13

Risk of anti-GBM disease in transplant as foreign type IV collagen may be recognised as foreign

Question 14

What is Fabry disease

Answer 14

X-linked lysosomal storage disorder due to alpha-galactosidase-A deficiency

Question 15

Fabry disease clinical features

Answer 15

Proteinuria
Progressive renal failure in most men + some female carriers
Lipid deposits seen in urine
Zebra body on renal biopsy

Question 16

Fabry disease treatment

Answer 16

IV enzyme replacement can stabilise kidney function if proteinuria controlled to <1g/24h

Question 17

What is Cystinuria

Answer 17

Autosomal recessive defect preventing cystine + dibasic aa reabsorption in proximal tubule, leading to cystinuria and cystine stone formation

Question 18

Cystinuria treatment

Answer 18

Low-cystine diet
Increased fluid intake
Urine alkalisation

Question 19

What is Cystinosis

Answer 19

Autosomal recessive lysosomal storage disorder with accumulation of cystine
Can cause proximal tubule dysfunction (Fanconi) in nephropathic forms

Question 20

Cystinosis presentation

Answer 20

Nephropathy
Visual impairment
Myopathy
Hypothyroidism

Question 21

Cystinosis treatment

Answer 21

Oral cysteamine decreases intralysosomal cystine and delays ESRF
Lots of SEs however (GI, skin deposits, fever, seizures)