Inherited disorders of the kidneys Flashcards
What are some types of inherited kidney disorders?
Cystic diseases
Familial glomerular syndromes
Inherited metabolic disease
What are some forms of inherited cystic diseases of the kidneys?
- Polycystic kidney disease
- Nephronophthisis
- Autosomal recessive PKD
- Medullary sponge kidney
- Tuberous sclerosis complex
- Von Hippel Lindau
- Simple cysts
What are some familial glomerular syndromes?
- Alports syndrome
- Fabrys disease
- Nail patella syndrome
- Congenital nephrotic syndrome
What are some inherited metabolic diseases affecting the kidneys?
- Cystinosis
- Hyperoxaluria
What are the 2 types of polycystic kidney disease?
Autosomal dominant PKD
Autosomal recessive PKD
What is the most frequent life-threatening hereditary kidney disease?
Autosomal dominant PKD
Describe the genetics of ADPKD
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
How does the gene involved in ADPKD affect prognosis?
Both have prognostic implications, with PKD1 patients developing end-stage kidney failure at an earlier stage
Describe the pathophysiology of ADPKD
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
What are some renal symptoms of ADPKD?
- Reduced urine concentration ability
- Chronic pain
- Hypertension
- Haematuria - Cyst rupture, cystitis, stones
- Cyst infection
- Renal failure
What are some extra-renal features of ADPKD?
Hepatic cysts
Intra-cranial aneurysms
Cardiac disease
Diverticular disease
Hernias
Describe the characteristics of hepatic cysts in ADPKD?
- Most common extra-renal manifestation
- Presents around 10 years after renal cysts
- Liver function usually preserved
- Can result in SOB, pain and ankle swelling
Describe the characteristics of intracranial aneurysms in ADPKD?
- 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
Describe the characteristics of cardiac disease in ADPKD?
Mitral/aortic valve prolapse - Collagenous/myxomatous degeneration
Describe the characteristics of diverticular disease in ADPKD?
- Increased prevalence and complications in those on dialysis
- Diverticulitis and colonic perforation are 2 serious complications
What investigations are required in ADPKD?
USS - Multiple bilateral cysts and enlargement
CT/MRI if unclear on USS
Mutation analysis
What is shown?
Polycystic kidney disease
How does ADPKD present in children?
- Utero or 1st year
- Similar renal involvement
- Cerebral aneurysms are rare
How can ADPKD and ARPKD be distinguished in children?
Congenital hepatic fibrosis on USS suggests recessive disease
What is the risk of a ADPKD patient’s child having the disease?
50%
How is ADPKD managed?
Hypertension control
Hydration
Cyst haemorrhage and infection monitoring
Tolvaptan
Renal failure management
What is Tolvaptan in ADPKD management?
An ADH receptor antagonist used to reduce cyst volume and progression by slowing loss of kidney function
Describe the genetics of autosomal recessive PKD
It has been linked to mutations of the PKDH1 gene on chromosome 6
Describe the pathophysiology of ARPKD
Renal involvement is usually bilateral and symmetrical
The urinary tract is generally normal
Describe the histology of ARPKD
Histologically, the cysts are seen appearing from the collecting duct system, with 30-90% of ducts showing involvement
What are some clinical features of ARPKD?
- Palpable kidneys
- Hypertension
- Recurrent UTIs
- Slow decline in GFR
What is the prognosis of ARPKD?
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
Describe the genetics and pathophysiology of Alport’s syndrome
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
How does Alpert’s syndrome present renally?
- Haematuria
- Proteinuria - Seen later and shows bad prognosis
What are some extra-renal symptoms of Alpert’s syndrome?
- Sensorineural deafness
- Occular defects - Anterior lenticonus
- Leiomyomatosis of oesophagus and genitalia - Rare
What should be suspected here:
microscopic haematuria +/- hearing loss
Alport’s syndrome
What investigations are required in Alport’s syndrome?
Renal biopsy
What will be seen on renal biopsy in Alport’s syndrome
Renal biopsy will show variable thickness of the GBM
How is Alport’s syndrome managed?
There is no specific treatment
There is standard aggressive BP and proteinuria management
Dialysis and transplantation may be required
Describe the genetics and pathophysiology of Anderson-Fabry’s disease
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
What are some cutaneous symptoms of Anderson-Fabry’s disease
Angiokeratomas
What are some cardiac symptoms of Anderson-Fabry’s disease
Cardiomyopathy
Valvular disease
What are some neurological symptoms of Anderson-Fabry’s disease?
Stroke
Acroparaesthesia
What are some renal features of Anderson-Fabry’s disease
Renal failure
How is Anderson-Fabry’s disease diagnosed?
- Blood tests showing low a-GAL activity in plasma/leukocytes
- Renal biopsy
- Skin biopsy
How is Anderson-Fabry’s disease managed?
- Enzyme replacement - Fabryzyme
- Management of complications
What is medullary cystic kidney disease?
This is a rare, autosomal dominant inherited cystic disease
Describe the histology of medullary cystic kidney disease
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
How is medullary cystic kidney disease diagnosed?
Family history
CT scan
When does medullary cystic kidney disease usually present
Average age of 28 years old
What is the management option for medullary cystic kidney disease
Renal transplant
What is medullary sponge kidney?
An uncommon, sporadic condition in which there is dilatation of the collecting duct with possible cyst formation
Describe the histology of medullary sponge kidney
In severe cases, the medullary area will look like a sponge
Cysts will often have calculi
How is medullary sponge kidney diagnosed?
excretion urography to demarcate the calculi
