inherited kidney disorders Flashcards
what is the mode of inheritance of polycystic kidney disease?
autosomal dominant (most common)
autosomal recessive
what is the most common ADPKD mutation?
mutation in the PKD gene 1, on chromosome 16- 85% of cases
PKD2 mutations, on chromosome 4- 15% of cases
which is worse- PKD1 or PKD2?
PKD1- they develop end stage kidney failure at an earlier stage
what is ADPKD pathology?
massive cyst enlargement= large kidneys
epithelial lined cysts arise from a small population of renal tubules
benign adenomas-25% of kidneys
what are the renal clinical features of ADPKD?
reduced urine concentration ability
chronic pain
hypertension- common and occurs early
haematuria- cyst rupture, cystitis, stones
cyst infection
renal failure
what are the extra renal clinical features of ADPKD?
hepatic cysts (most common extra renal manifestation)
- can result in SOB, pain, Ankle swelling
intracranial aneurysms (4-8% of Pts)
- seen in clusters of family members and usually seen in the anterior circulation territory
cardiac- mitral/aortic valve prolapse
diverticular disease
hernias-abdominal/inguinal
how is ADPKD diagnosed?
radiologic
-USS: presence of multiple bilateral cysts
: renal enlargement
-CT/MRI used when USS is unclear
genetic
- linkage analysis
- mutation analysis
what are the features of ADPKD in children?
early onset- can be in utero or first year of life
siblings are at increased risk
renal involvement in similar to adults
a single cyst in high risk pts is enough to diagnose
cerebral aneurysms rare in children
USS suggestion of congenital hepatic fibrosis suggests recessive disease
if someone with ADPKD has a child, what is the likelihood of them having ADPKD?
50%
what is the management of ADPKD?
hypertension- rigorous control
hydration
proteinuria reduction
tolvaptan (ADH receptor antagonist) reduces cyst volume and progression
what are the features of ARPKD?
associated with hepatic fibrosis lesions
mutation occurs on chromosome 6
renal involvement is bilateral and symetrical
urinary tract is generally normal
where do cysts appear in ARPKD?
seen appearing from the collecting duct system
what is the clinical presentation of ARPKD?
kidneys are always palpable
hypertension
recurrent UTIs
slow decline in GFR- less than 1/3 reach dialysis
what is alports syndrome?
hereditary nephritis
X linked inheritance
disorder of type IV collagen matrix
mutation in the COL4A5 gene
what are the signs and symptoms of alports syndrome?
haematuria
proteinuria seen later but= bad prognosis
sensorineural deafness
ocular defects- anterior lenticonus
leiomyomatosis of oesophagus/genitalia (rare)
how is alports diagnosed?
suspect in patients with microscopic haematuria +/- hearing loss
renal biopsy will show a variable thickness GBM
what is the treatment of alports?
no specific treatment
aggressive treatment of BP, proteinuria
dialysis/transplantation
what are the features of anderson fabrys disease?
deficiency of a-galactosidase A
X linked disease lysosomal storage disease
affects kidneys, liver, lungs, erythrocytes
uncommon
what are the clinical features of anderson fabrys disease?
renal failure
angiokeratomas
cardiomyopathy, valvular disease
stroke, acroparaethesia
psychiatric
how is fabrys diagnosed?
concentric lamellar inclusions within lysosomes
a-GAL activity of leukocytes
renal biopsy
skin biopsy
how is anderson fabrys disease treated?
enzyme replacement- fabryzyme
management of complications
what are the features of medullary cystic kidney?
rare autosomal dominant disease
abnormal renal tubules leading to fibrosis
affects small kidneys
where do cysts occur in the medullary cystic kidney?
in the corticomedullary junction/medulla
how is medullary cystic kidney diagnosed?
family history, CT scan
