Week 4 - H - Inheritied kidney disorders - P.K.D / Potter's, Alport's, Anderson-Fabry, Medullary cystic Flashcards
What are the two main types of polycystic kidney disease and which is more common?
Autosmoal dominant and autosomal recessive polycystic kidney disease
Autosomal dominant is more common
Where do the cysts in PKD occur?
The cysts occur in the cortex and medulla of the kidneys therefor impeding function
ADPKD is an important cause of ESRD
What stage of CKD is ESRD?
This is stage 5 - GFR <15 and patinet is on dialysis and prevelance is 0.1%
What are the mutations in ADPKD? State which is more common?
85% is a mutation in PKD gene 1 on chromosome 16
15% is a mutation in PKD gene 2 on chromosome 4
Why is genetic counselling important in a patinet with autosomal dominant polycystic kidney disease?
This is because the disease is autosomal dominant and therefore 50% of offsrping is likely to have the disease
ADPKD presents in young adults usually What are the renal symptoms and signs?
Abdominal pain haematuria - rupture cyst
Big and palpable kidneys on balloting
Bilateral also
Progressive renal failure
What happens to the urine production in ADPKD?
There is a reduced urine concentrating ability due to the cysts causing the kidney to be damaged and therfore the patient can experience enuresis
What are extra renal signs of ADPKD? (ie what other organs are affected by the cysts and what is a really important other sign)
Hepatic and pacnreatic cysts usually on Ultrasound - usually non functioning
Ovarian cysts can also occur
Intra-cranial anuerysm - sub arachnoid haemorrhage - due to berry aneursym in circle of Willis rupturing
(big bilateral and berry aneurysms)
What is the heart defects seen in ADPKD?
Tend to see mytral/aortic valve prolapse
What is used for diagnosis of ADPKD?
Ultrasound examination to detect renal cysts
If unsure of cysts on ultrasound, what is carried out?
Carry out CT scan to detect for cysts
Autosomal dominant polycystic kidney disease in children can be difficult to differentiate from autosomal recessive PKD
If the ultrasound detects ______ when examining, how will this point more to ARPKD?,
On USS, the presence of suspicion of congenital hepatic fibrosis is associated with ARPKD
In ADPKD, the urea and electrolytes need to be monitored What is the best option to control the blood pressure? What is the new treatment to reduce cyst volume and progression?
For the hypertension - prescribe ACEinhbitors
To reduce the cyst volume and progression - Tolvaptan
What type of drug is tolvaptan?
it is a vasopressin antagonist
If the patinet is in end stage renal failure, what is the treatment option?
Treat the patient with dialysis or transplant therapy
What is the rarer form of polycytic kidney disease and what is the mutation?
This is autosomal recessive polycystic kidney disease - presents in children
Mutation in ARPKD is on the PKHD1 gene (polycystic kidney and hepatic disease 1) on chromosome 6
What is the sydrome that can occur in newborns affected by polycystic kidney disease also seen in newborns with bilateral renal agenesis?
Potter’s syndrome - due to oligohydroamnios (deficiency of amniotic fluid)
What are the features of potter’s syndrome?
Lung hypoplasia
Flat face and low set ears
Developmental defects of the limbs - due to oligohydroaminos
5In ARPKD, there is bilateral renal involement with elongated cycts often causing medullary collecting duct dilatation What is ARPKD also associated with? (another congenital thing)
Congenital hepatic fibrosis which can lead to hypertension and hepatic cysts
What is the clinical presentation of ARPKD?
Child presents with bilateral renal enlagrment
Is hypertensive, recurrent UTIs and kidneys are palpable
In children with ARPKD, the investigation is done with a US/CT What percentage of children are expected to even reach dialysis?
Only 1/3rd of children reach dialsysis
a genetic condition characterized by kidney disease, hearing loss, and eye abnormalities. What is this condition known as? 1-2% of patients end up with ESRD
This is Alport’s syndrome
What is the muation of Alport’s syndrome and how is it passed on?
It is an X-linked inheritance where there is defect in the type IV collagen maturation
What are the clincial defects of Alport’s syndrome?
Hameaturia
Sensorineural deafness
Ocular defects
Proteinuria - worse prognosis if this is here
What is the ocular defect in Alport’s syndrome known as?
Anterior lenticonus - they patient has a misshapen lens where the lens protrudes into the anterior chamber of the eye
When a patinet presents with haematuria and sensorineural deafness, Alport’s is suspected What is the test carried out?
Carry out a renal biopsy which shows variable thickness glomerular basement membrane which is a charcteristic feature
What is given to control the preoteinuria and blood pressure in Alport’s?
Give ACE inhibtor
In patients progressing to ESRD - dialysis and transplantation are considered
X linked lysosomal storage disease with Inborn error of glycosphingolipid metabolism What is the deificency in and hwat is the disease?
Anderosn-Fabry’s disease - deficiency of a-galactosidaseA
What are the organs affected by anderson-Fabry’s disase?
The kidneys, livers, lungs and erythrocytes
Run over again, what is Anderson’fabry’s disease?
It is an X lnked inheritance a-galactosidase
A deficiecny causing in error in lysosomal storage with an inborn error of glycosphingolipid metabolism
How is Anderson-Fabry’s disease diagnosed?
It is diagnosed by measuring a-GAL A or Renal or skin biopsy
What are the clinical features of Anderson-Fabry’s disease?
Renal failure
Cutaenous lesions
Cardiomyopathy / valvular disease
Stroke
What are the cutaneous lesions seen in Aderson-Fabry’s disease known as?
These cutaneous lesions are known as angiokeratomas
What do angiokertomas look like?
They look like small red/blue papules on the skin
What is the treatmnet of Anderson-Fabry’s disease?
Treat with enzyme replacement therapy - fabryzyme (man-made alpha-glactosidase A)
One more time what is the defect in Anderson-Fary’s disease? What is wrong in Alport’s disease?
Anderson Fabry - Xlinked lysosomal storage disease with an inborn error of glycosphingolipid metabolsim (deficiency of alpha-galactosidase A)
Alport’s - defect in type IV collagen maturation - leads to haematuria, sensorinerual deafness, ocular defects (anterior leticnus) and proteinuria if severe
Inherited (autosomal dominant) defect leading to cysts in the medullary collecting ducts causing enal fibrosis What is this disorder?
This is medullary cystic disease
What does the parenchymal fibrosis due to the cysts result in? (size and function of the kidneys)
This results in shrunken kidneys and renal failure as the kidneys lose their ability to concentrate the urine
What are symptoms of medullary cystic kidney disease? What does PKD have that this does not as symptoms?
Medullary - polyuria, polydispia, enuresis
PKD will also have a heavy felling in the back and abdominal pain with haematuria
Medullary cystic disease is diagnosed by CT scan, what is the age of presentation and what is the treatment?
Roughly 28 years and renal transplant is treatment of choice
Patinet presents with sensorineural loss, haematuria and proteinuria What is the other clinical feature? What is the disease? What is the treatment? What is the defect?
Patinet has Alport’s syndrome
Also associated with anterior leticonus (bilateral here)
Defect in type IV collagen maturation - Xlinked Treatment is using ACEinhibtors
