Inherited disorders of the kidneys Flashcards
What is the most common hereditary cause of end stage renal failure ?
Autosomal dominant polycystic kidney disease
What are the mutations which cause autosomal dominant polycystic kidney disease ?
- PKD 1 on chromosome 16 - seen in 85% of cases
- PKD 2 on chromosome 4 - seen in 15% of cases
What is the appearance of the kidneys in autosomal dominant polycystic kidney disease(ADPKD) ?
Massive renal enlargement with cysts
What are the renal signs of AKPKD?
- Abdominal pain
- Haematuria
- Increased BP
- Renal calculi
- Cyst infection
- Progressive renal failure
What are the extra-renal features of ADPKD?
- Liver cysts
- Intra-cranial aneurysms ==> subarachnoid haemorrhage
- Mitral valve prolapse
- Ovarian cysts
- Diverticular disease - diverticulitis
- Hernias
How is ADPKD diagnosed ?
- 1st line = US
- 2nd line = abdominal CT/MRI if US unclear
- 3rd line = if imaging studies inconclusive then do genetic testing for PKD1 or PKD2 mutation
What is the management of PKD ?
- Hydration
- Proteinuria reduction
- Cyst Haemorrhage+ Cyst Infection
- New treatment –to reduce cyst volume and progression – Tolvaptan
- Renal Failure - management of CKD
- Pain may be helped by laproscopic cyst removal or nephrectomy
What genetic mutation causes autosomal recessive polycystic kidney disease ?
PKDH1 on chromosome 6
Histologically where do the cysts appear from in ARPKD ?
Appear from the collecting duct system
What is the typical presentation of ARPKD ?
Infant with multiple renal cysts and congenital hepatic fibrosis
What is the prognosis for ARPKD ?
- Infants who survive the neonatal period have a mortality rate of 9% to 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
What is the treatment for ARPKD ?
No specific therapy
What is the genetic mutation causing alports syndrome ?
Mutation COL4A5 gene
Due to the genetic mutation causing alports syndrome what defect does this result in ?
Results in disorder of type IV collagen - resulting in an abnormal glomerular-basement membrane (GBM).
What is the mode of inheritance of alports syndrome ?
X-linked
What are the signs of alports syndrome ?
- Microscopic haematuria - this is key
- Proteinuria - seen a bit later on
- Progressive renal insufficiency (CKD)
- Bilateral sensorineural deafness
- Ocular manifestations - retinitis pigmentosa, lenticonus
What are the 2 key signs which would make you suspect alports syndrome ?
Haematuria and hearing loss
How is alports syndrome diagnosed and what is seen ?
Renal biopsy - shows thickening of the glomerular basement membrane (GBM) with splitting
What is the treatment of alports syndrome ?
- No specific treatment
- Treat the CKD it causes as normal
What is anderson fabrys disease?
X-lined lysosome storage disorder caused by mutations in the GLA gene
What are people with anderson fabrys disease deficient in ?
a-galactosidase A
What are the features of anderson fabrys disease ?
- Renal failure
- Cutaneous-Angiokeratomas
- Cardiac-cardiomyopathy, valvular disease
- Neurological- stroke,acroparaesthesia
- Psychiatric
How is anderson fabrys disease diagnosed ?
- Plasma /Leukocyte a-GAL activity
- Renal Biopsy
- Skin Biopsy
What is the treatment of anderson fabrys disease ?
- Enzyme replacement- (alpha or beta agalsidase) Fabryzyme
- Management of Complications - e.g. CKD treatment
What is medullary cystic kidney disease
Rare inherited cystic disease- Autosomal Dominant inheritance
What is the appearance of medullary cystic kidney disease ?
- Shruken kidneys (cortex and medulla both shrunken)
- Cysts restricted to the medulla
- Abnormal renal tubules leading to fibrosis
How is medullary cystic kidney disease diagnosed ?
Family history and CT scan
What is the treatment for medullary cystic kidney disease ?
Renal Transplantation
