Inherited kidney disorders

Question 1

ADPKD - definition

Answer 1

Autosomal dominant polycystic kidney disease

Massive bilateral renal enlargement

Question 2

ADPKD - who gets it?

Answer 2

Adults (mid-life)

All races and ethnic groups affected

Question 3

ADPKD - genetics

Answer 3

PKD gene 1 mutations - chromosome 16

PKD gene 2 mutations - chromosome 4

Question 4

ADPKD - which is the most commonly mutated gene?

Answer 4

PKD1 - chromosome 16

Question 5

ADPKD - pathology

Answer 5

Massive bilateral renal enlargement
Kidneys are >1kg
Subsequent reduction in renal function
Multiple cysts of varying size cause a distortion of kidney shape
Cysts can arise at any part of the nephron

Question 6

In ADPKD, cysts are confined to the kidneys. True or False?

Answer 6

False

• common to get cysts in other organs (e.g. liver)
• there is no functional effect at these other organ sites

Question 7

ADPKD - clinical features (renal)

Answer 7

Reduced urine concentration ability
Chronic pain
Abdominal fullness
Haematuria - if cysts rupture

Question 8

ADPKD - clinical features (extra-renal)

Answer 8

Hypertension - often presents early
Hepatic cysts 
Berry aneurysms - at circle of willis 
Cardiac disease
Diverticular disease
Hernias

Question 9

ADPKD - Patient presents with headaches and subsequent loss of consciousness. What is the most likely cause?

Answer 9

Berry aneurysm

Question 10

ADPKD - what is the most likely extra renal manifestation ?

Answer 10

Hepatic cysts

Question 11

ADPKD - investigations

Answer 11

US

• presence of multiple bilateral cysts
• renal enlargement

X-ray
- cyst calcification in the renal area

CT/MRI
- only if unclear findings on US

Question 12

ADPKD - management

Answer 12

Hypertension control 
Hydration
Proteinuria reduction
- ACE inhibitors / ARBs
Tolvaptan
- CA which reduces cyst volume and progression
- causes increased urine production

Question 13

ADPKD in children

Answer 13

Rare

A single cyst in the kidney in high risk pts is enough for diagnosis

Question 14

ARPKD - definition

Answer 14

Autosomal Recessive Polycystic Kidney Disease

Uniform bilateral renal enlargement

Question 15

What is the most frequent life threatening hereditary disease

Answer 15

Polycystic kidney disease

Question 16

ARPKD - who gets it

Answer 16

Young children

- commonly occurs immediately after birth

Question 17

ARPKD - genetics

Answer 17

PKDH1 on chromosome 6

Question 18

ARPKD - pathology

Answer 18

Kidneys become enlarged but their shape is maintained
No gross distortion of kidney
Cysts appear from the collecting duct system
Dilation of collecting ducts in the distal part of the nephron

Question 19

ARPKD - associated diseases

Answer 19

Congenital hepatic fibrosis

Question 20

ARPKD - clinical features

Answer 20

Varies from person-person
Kidneys are palpable
Hypertension
Recurrent UTI

Question 21

ARPKD - investigations

Answer 21

GFR
- slow decline

CT
- renal enlargement is bilateral and symmetrical

Question 22

Where do cysts appear from in ARPKD ?

Answer 22

Collecting duct system

Question 23

ARPKD - prognosis

Answer 23

If children survive past the first year of life then most will survive beyond 15 years

Question 24

Alports syndrome - definition

Answer 24

disorder of the glomerular basement membrane

Disorder of type IV collagen matrix deposition

Question 25

Alport syndrome - genetics

Answer 25

X linked inheritance | Mutation (COL4A5 gene) leads to deficient collagenous matrix

Question 26

Alport syndrome - clinical features

Answer 26

``` Haematuria Proteinuria Hearing loss Ocular defect Dysphagia ```

Question 27

Alport syndrome - investigations

Answer 27

Renal biopsy | - variable thickness of the glomerular basement membrane

Question 28

Alport syndrome - management

Answer 28

No specific treatment Control BP Control proteinuria RRT

Question 29

Fabrys disease - definition

Answer 29

Lysosomal storage disease | Deficiency of alpha-galactosidase A which causes an accumulation of waste products in the body

Question 30

Fabrys disease - genetics

Answer 30

X linked | rare

Question 31

Fabrys disease - clinical features

Answer 31

``` Pain - either chronic or acute Cutaneous: angiokeratomas - dark red spots Renal failure Cardiomyopathy Valvular disease Stroke ```

Question 32

Fabrys disease - Investigations

Answer 32

Renal biopsy - lamellar inclusions Skin biopsy - angiokeratomas (telangectasia) in the umbilical area

Question 33

Fabrys disease - management

Answer 33

Enzyme replacement (fabryzyme)

Question 34

Medullary cystic disease - definition

Answer 34

Morphologically abnormal renal tubules leading to fibrosis

Question 35

Medullary cystic disease - genetics

Answer 35

Autosomal dominant

Question 36

Medullary cystic disease - pathology

Answer 36

Cortex and medulla are shrunken | Irregularly distributed cysts of variable size in the aorticomedullary junction / medulla

Question 37

Medullary cystic disease - investigations

Answer 37

CT scan - no enlarged cysts - fibrosis of tubules

Question 38

Medullary cystic disease - management

Answer 38

Renal transplantation

Question 39

Medullary sponge kidney - definition

Answer 39

Dilation of the collecting ducts | Medulla appears like a sponge

Question 40

Medullary sponge kidney - Investigations

Answer 40

Excretion urography | - cysts have calculi