Inherited disorders of the kidneys

Question 1

What are some types of inherited kidney disorders?

Answer 1

Cystic diseases
Familial glomerular syndromes
Inherited metabolic disease

Question 2

What are some forms of inherited cystic diseases of the kidneys?

Answer 2

• Polycystic kidney disease
• Nephronophthisis
• Autosomal recessive PKD
• Medullary sponge kidney
• Tuberous sclerosis complex
• Von Hippel Lindau
• Simple cysts

Question 3

What are some familial glomerular syndromes?

Answer 3

• Alports syndrome
• Fabrys disease
• Nail patella syndrome
• Congenital nephrotic syndrome

Question 4

What are some inherited metabolic diseases affecting the kidneys?

Answer 4

• Cystinosis
• Hyperoxaluria

Question 5

What are the 2 types of polycystic kidney disease?

Answer 5

Autosomal dominant PKD
Autosomal recessive PKD

Question 6

What is the most frequent life-threatening hereditary kidney disease?

Answer 6

Autosomal dominant PKD

Question 7

Describe the genetics of ADPKD

Answer 7

In 85% of cases, it is caused by mutations of PKD1 gene, located on chromosome 16

In 15% of cases, it is caused by mutations of PKD2 gene, located on chromosome 4

Question 8

How does the gene involved in ADPKD affect prognosis?

Answer 8

Both have prognostic implications, with PKD1 patients developing end-stage kidney failure at an earlier stage

Question 9

Describe the pathophysiology of ADPKD

Answer 9

This will result in the formation of epithelial lined cysts arising from a small population of renal tubules

In some cases, these cysts may enlarge and cause kidney enlargement

In some cases, benign adenomas may form, which need to be monitored for malignant transformtion

Question 10

What are some renal symptoms of ADPKD?

Answer 10

• Reduced urine concentration ability
• Chronic pain
• Hypertension
• Haematuria - Cyst rupture, cystitis, stones
• Cyst infection
• Renal failure

Question 11

What are some extra-renal features of ADPKD?

Answer 11

Hepatic cysts
Intra-cranial aneurysms
Cardiac disease
Diverticular disease
Hernias

Question 12

Describe the characteristics of hepatic cysts in ADPKD?

Answer 12

• Most common extra-renal manifestation
• Presents around 10 years after renal cysts
• Liver function usually preserved
• Can result in SOB, pain and ankle swelling

Question 13

Describe the characteristics of intracranial aneurysms in ADPKD?

Answer 13

• Seen in 4-8% of patients
• Seen in clusters of family members
• Mainly seen in the anterior circulation territory
• Screening indicated in those with a family history

Question 14

Describe the characteristics of cardiac disease in ADPKD?

Answer 14

Mitral/aortic valve prolapse - Collagenous/myxomatous degeneration

Question 15

Describe the characteristics of diverticular disease in ADPKD?

Answer 15

• Increased prevalence and complications in those on dialysis
• Diverticulitis and colonic perforation are 2 serious complications

Question 16

What investigations are required in ADPKD?

Answer 16

USS - Multiple bilateral cysts and enlargement
CT/MRI if unclear on USS
Mutation analysis

Question 17

What is shown?

Answer 17

Polycystic kidney disease

Question 18

How does ADPKD present in children?

Answer 18

• Utero or 1st year
• Similar renal involvement
• Cerebral aneurysms are rare

Question 19

How can ADPKD and ARPKD be distinguished in children?

Answer 19

Congenital hepatic fibrosis on USS suggests recessive disease

Question 20

What is the risk of a ADPKD patient’s child having the disease?

Answer 20

50%

Question 21

How is ADPKD managed?

Answer 21

Hypertension control
Hydration
Cyst haemorrhage and infection monitoring
Tolvaptan
Renal failure management

Question 22

What is Tolvaptan in ADPKD management?

Answer 22

An ADH receptor antagonist used to reduce cyst volume and progression by slowing loss of kidney function

Question 23

Describe the genetics of autosomal recessive PKD

Answer 23

It has been linked to mutations of the PKDH1 gene on chromosome 6

Question 24

Describe the pathophysiology of ARPKD

Answer 24

Renal involvement is usually bilateral and symmetrical

The urinary tract is generally normal

Question 26

Describe the histology of ARPKD

Answer 26

Histologically, the cysts are seen appearing from the collecting duct system, with 30-90% of ducts showing involvement

Question 27

What are some clinical features of ARPKD?

Answer 27

- Palpable kidneys - Hypertension - Recurrent UTIs - Slow decline in GFR

Question 28

What is the prognosis of ARPKD?

Answer 28

30-50% of children with ARPKD are severely affected Infants who survive the neonatal period have a mortality rate of 9-24% in the first year of life Children who survive the first year of life have a relatively good prognosis with a survival probability of 80% beyond 15 years

Question 29

Describe the genetics and pathophysiology of Alport's syndrome

Answer 29

This is an X-linked conditions (In 85% of cases), with a mutation in the COL4A5 gene, which leads to a deficient collagenous matrix deposition due to disorder of type IV collagen

Question 30

How does Alpert's syndrome present renally?

Answer 30

- Haematuria - Proteinuria - Seen later and shows bad prognosis

Question 31

What are some extra-renal symptoms of Alpert's syndrome?

Answer 31

- Sensorineural deafness - Occular defects - Anterior lenticonus - Leiomyomatosis of oesophagus and genitalia - Rare

Question 32

What should be suspected here: microscopic haematuria +/- hearing loss

Answer 32

Alport's syndrome

Question 33

What investigations are required in Alport's syndrome?

Answer 33

Renal biopsy

Question 34

What will be seen on renal biopsy in Alport's syndrome

Answer 34

Renal biopsy will show variable thickness of the GBM

Question 35

How is Alport's syndrome managed?

Answer 35

There is no specific treatment There is standard aggressive BP and proteinuria management Dialysis and transplantation may be required

Question 36

Describe the genetics and pathophysiology of Anderson-Fabry's disease

Answer 36

This is an X-linked lysosomal storage disease caused by an inborn error of glycosphingolipid metabolism, causing a deficiency of a-galactosidase A) This affects the kidneys, liver, lungs and erythrocytes

Question 37

What are some cutaneous symptoms of Anderson-Fabry's disease

Answer 37

Angiokeratomas

Question 38

What are some cardiac symptoms of Anderson-Fabry's disease

Answer 38

Cardiomyopathy Valvular disease

Question 39

What are some neurological symptoms of Anderson-Fabry's disease?

Answer 39

Stroke Acroparaesthesia

Question 40

What are some renal features of Anderson-Fabry's disease

Answer 40

Renal failure

Question 41

How is Anderson-Fabry's disease diagnosed?

Answer 41

- Blood tests showing low a-GAL activity in plasma/leukocytes - Renal biopsy - Skin biopsy

Question 42

How is Anderson-Fabry's disease managed?

Answer 42

- Enzyme replacement - Fabryzyme - Management of complications

Question 43

What is medullary cystic kidney disease?

Answer 43

This is a rare, autosomal dominant inherited cystic disease

Question 44

Describe the histology of medullary cystic kidney disease

Answer 44

Morphology shows abnormal renal tubules leading to fibrosis The affected kidneys will be either normal sized or smaller Cysts are found in the corticomedullary junction or the medulla

Question 45

How is medullary cystic kidney disease diagnosed?

Answer 45

Family history CT scan

Question 46

When does medullary cystic kidney disease usually present

Answer 46

Average age of 28 years old

Question 47

What is the management option for medullary cystic kidney disease

Answer 47

Renal transplant

Question 48

What is medullary sponge kidney?

Answer 48

An uncommon, sporadic condition in which there is dilatation of the collecting duct with possible cyst formation

Question 49

Describe the histology of medullary sponge kidney

Answer 49

In severe cases, the medullary area will look like a sponge Cysts will often have calculi

Question 50

How is medullary sponge kidney diagnosed?

Answer 50

excretion urography to demarcate the calculi