inherited disorders of the kidney Flashcards
Polycystic Kidney Disease can be
autosomal dominantly or autosomally recessively inherited
most common type of polycystic kidney disease
autosomal dominant inheritance
polycystic kidney disease is the
4th leading cause of end stage renal failure
polycystic kidney disease causes the formation of
fluid filled cysts within the kidneys
autosomal dominant PKD is either caused by a
mutation of the PKD gene 1 on chromosome 16 or mutation of the PKD gene 2 on chromosome 4
mutations of the PKD gene 1 causes
end stage renal failure earlier than mutations of the PKD gene 2
in autosomal dominant polycystic kidney disease affected individuals have a
50% chance of having an affected child
autosomal dominant polycystic kidney disease causes massive
cyst enlargement causing abnormally large kidneys, epithelial lined cysts arise from a small population of renal tubules
presentation of autosomal dominant polycystic kidney disease
most people are completely asymptomatic early in the disease and don’t get symptoms until they are in there 30s and 40s
renal features of ADPKD
- reduced ability to concentrate urine causes excessive urination
- pain due to stretching of the renal capsule
- haematuria if the cyst ruptures
- cyst infections
- kidney stones
extra- renal features of ADPKD
- hypertension
- hepatic cysts are the most common extra-renal manifestation they tend to present 10 years after renal cysts, but they don’t cause any disruption to renal function can sometime cause fluid retention causing ankle oedema and shortness of breath
- intra-cranial aneurysms tend to occur in the anterior circulation and if they rupture they can cause a haemorrhage stroke
- cardiac disease= mitral/ aortic valve prolapse.colalgenous/ myxomatous degeneration
- diverticular disease has an increase prevalence and complications in those with autosomal dominant polycystic kidney disease who are on dialysis
- hernias= increased incidence of abdominal and inguinal hernias
screening for intra-cranial aneurysms is indicated in those
who have autosomal dominant polycystic kidney disease and have a family history of intra-cranial aneurysms however, it is not indicated in every person with autosomal dominant polycystic kidney disease
diagnosis of autosomal dominant polycystic kidney disease
- diagnosed on ultrasound which shows multiple enlarged bilateral cysts and renal enlargement
if ultrasound in inconclusive for the diagnosis of autosomal dominant polycystic kidney disease
MRI
If someone does not have genetic diagnosis with polycystic disease what should they be referred for
mutation analysis
autosomal dominant PKD does not usually present in who?
children however an early onset can be in utero or in the first year of life and suggests an aggressive mutation
autosomal dominant polycystic kidney disease is difficult to distinguish from what
autosomal recessive polycystic kidney disease but hepatic fibrosis on ultrasound suggests autosomal recessive disease rather than autosomal dominant disease
management of autosomal dominant polycystic kidney disease
- very rigorous hypertension control and adequate hydration
- new treatment called TOLVAPTAN
What is tolvaptan
a vasopressin V2 receptor antagonist
indications for usage of tolvaptan
autosomal dominant polycystic kidney disease in adults with chronic kidney disease stage 1-3 at initiation of treatment and evidence of rapidly progressive disease
autosomal dominant polycystic kidney disease will eventually cause
end stage renal failure and require dialysis and transplant
autosomal recessive polycystic kidney disease
is much less common that autosomal dominant polycystic kidney disease
in autosomal recessive polycystic kidney disease
both parents must have the mutation for there child to be affected by the disease
autosomal recessive polycystic kidney disease is caused by mutation
of the PKHD1 gene on chromosome 6
renal involvement in autosomal recessive polycystic kidney disease is
bilateral and symmetrical
cysts in autosomal recessive polycystic kidney disease are seen appearing
from the collecting duct system
autosomal recessive polycystic kidney disease is always associated with
hepatic diseased the kidneys are ALWAYS palpable
clinical présentation of autosomal recessive polycystic kidney disease is
variable depending on the severity of the disease, but not many survive the neonatal period however, if they do survey the neonatal period it has a good prognosis with only one third progressing to end stage renal failure
acquired cystic kidney disease
is not inherited and usually occurs later on in life
acquired cystic kidney disease usually occurs in those
who have underlying kidney problems i.e. it is more common in people with kidney failure or those who are on dialysis
alport syndrome is caused by
mutations of type 4 collagen
type 4 colagen is important in
- glomerulus of the kidney
- eye
- cochlea
type 4 collagen is found in
all basement membranes
basement membrane structure
- lamina lucida
- lamina densa
- lamina reticularis
basement membrane of the glomerulus in alports syndrome becomes
abnormally thin and overly porous which allows red blood cells to enter the filtrate causing a micro-haematuria which can lead to macroscopic haematuria, over time proteins also get into the filtrate causing a proteinuria which eventually leads to glomerulosclerosis which can result in renal failure and reno-vascualr hypertension
collectively the haematuria, renal insufficiency and hypertension contribute to the categorisation of aport syndrome as a
glomerulonephritis
why is the ear affected in alports syndrome
because in the organ of court the hair cells are attached to a basement membrane, abnormal type 4 collagen prevents the hair cells from generating normal nerve signals in response to sound vibrations
type of hearing loss in alport syndrome
sensinoneural
alport syndrome can also cause
anterior lenticonus where the middle part of the lens starts to push into the anterior chamber because the anterior lens capsule lacks integrity to maintain the shape of the lens
type 4 collagen is
a heterodimer which means it is made up of 3 different polypeptide subunits each made up of aha chains which fit together into a triple helix
each alpha chain has
a repetitive amino acid sequence
most common form of alport syndrom is caused by a mutation of the
COL4A5 gene on the X chromosome which is why it is a form of X linked inheritance
alport syndrome can also be caused by a mutation of the
COL 4A3 OF COL4A4 GENE which are present on autosomes and would be inherited autosomal dominantly or autosomal recessively
suspect alport syndrome in anyone with
haematuria and hearing loss
diagnosis of aport syndrome
Skin or kidney biopsy and analysis using immunohistochemisrty or biopsy can be analysed using electron microscopy which show variable thickness of the glomerular basement membrane
treatment of aport syndrome
aggressive management of proteinuria using ACE inhibitors or angiotensin receptor blockers
- will eventually require analysis or renal transplant
Anderson Fabrys disease
X linked lysosomal storage disorder which causes a deficiency in the enzyme alpha- galactosidase A
anderson fabrys disease affects
the liver, lungs, kidneys and erythrocytes
anderson fabrys disease causes a build up of
ceramide trihexoside
clinical features of anderson fabrys disease
renal failure, cutaneous angiokeratoma, cardiomyopathy, stroke, acroparaesthesia
diagnosis of anderson fabrys disease
enzyme assay measuring the amount of alpha- GAL enzyme
treatment of anderson fabrys disease
enzyme replacement using fabryzyme
medullary cystic kidney disease inherited
autosomal dominantly
medially cystic kidney disease causes
tubuluo-interstitial fibrosis and inflammation, tubular atrophy, cysts in the cortico-medually junction and eventually causes glomerulosclerosis
medullary cystic kidney disease is caused by mutation in
MUC1 gene
medially cystic kidney disease causes
polyuria ,polydipsia due to inability to concentrate urine, sats wasting eventually causing renal failure
treatment of medially cystic kidney disease
renal transplant
medullary sponge kidney
medullar of the kidney becomes spongy
medullary sponge kidney is inherited
not inherited and occurs sporadically
during foetal development
the mesonephric duct has a structure called the ureteric bud which pushes its way into the metanephric blastema at week 5 gestation, together these 2 structures start to form the kidney
- ureteric bud forms the ureters, renal calyxes, collecting ducts and the collecting tubules
- metanephric blastema forms the nephron itself
medullary sponge kidney is thought to be due to
abnormal induction of the metanephring blastema by the ureteric duct causing dilation of the collecting ducts and small cysts forming in the collecting duct
medullary spoke kidney does not cause
renal failure
medullary sponge kidney causes
nephrolithiasis (renal stones) in the collecting ducts because there is failure of the kidney to re-absorbe and secrete solutes
diagnosis of medullary sponge kidney
IV pyelogram
