inherited disorders of the kidney

Question 1

Polycystic Kidney Disease can be

Answer 1

autosomal dominantly or autosomally recessively inherited

Question 2

most common type of polycystic kidney disease

Answer 2

autosomal dominant inheritance

Question 3

polycystic kidney disease is the

Answer 3

4th leading cause of end stage renal failure

Question 4

polycystic kidney disease causes the formation of

Answer 4

fluid filled cysts within the kidneys

Question 5

autosomal dominant PKD is either caused by a

Answer 5

mutation of the PKD gene 1 on chromosome 16 or mutation of the PKD gene 2 on chromosome 4

Question 6

mutations of the PKD gene 1 causes

Answer 6

end stage renal failure earlier than mutations of the PKD gene 2

Question 7

in autosomal dominant polycystic kidney disease affected individuals have a

Answer 7

50% chance of having an affected child

Question 8

autosomal dominant polycystic kidney disease causes massive

Answer 8

cyst enlargement causing abnormally large kidneys, epithelial lined cysts arise from a small population of renal tubules

Question 9

presentation of autosomal dominant polycystic kidney disease

Answer 9

most people are completely asymptomatic early in the disease and don’t get symptoms until they are in there 30s and 40s

Question 10

renal features of ADPKD

Answer 10

• 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

Question 11

extra- renal features of ADPKD

Answer 11

• 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

Question 12

screening for intra-cranial aneurysms is indicated in those

Answer 12

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

Question 13

diagnosis of autosomal dominant polycystic kidney disease

Answer 13

• diagnosed on ultrasound which shows multiple enlarged bilateral cysts and renal enlargement

Question 14

if ultrasound in inconclusive for the diagnosis of autosomal dominant polycystic kidney disease

Answer 14

MRI

Question 15

If someone does not have genetic diagnosis with polycystic disease what should they be referred for

Answer 15

mutation analysis

Question 16

autosomal dominant PKD does not usually present in who?

Answer 16

children however an early onset can be in utero or in the first year of life and suggests an aggressive mutation

Question 17

autosomal dominant polycystic kidney disease is difficult to distinguish from what

Answer 17

autosomal recessive polycystic kidney disease but hepatic fibrosis on ultrasound suggests autosomal recessive disease rather than autosomal dominant disease

Question 18

management of autosomal dominant polycystic kidney disease

Answer 18

• very rigorous hypertension control and adequate hydration

- new treatment called TOLVAPTAN

Question 19

What is tolvaptan

Answer 19

a vasopressin V2 receptor antagonist

Question 20

indications for usage of tolvaptan

Answer 20

autosomal dominant polycystic kidney disease in adults with chronic kidney disease stage 1-3 at initiation of treatment and evidence of rapidly progressive disease

Question 21

autosomal dominant polycystic kidney disease will eventually cause

Answer 21

end stage renal failure and require dialysis and transplant

Question 22

autosomal recessive polycystic kidney disease

Answer 22

is much less common that autosomal dominant polycystic kidney disease

Question 23

in autosomal recessive polycystic kidney disease

Answer 23

both parents must have the mutation for there child to be affected by the disease

Question 24

autosomal recessive polycystic kidney disease is caused by mutation

Answer 24

of the PKHD1 gene on chromosome 6

Question 25

renal involvement in autosomal recessive polycystic kidney disease is

Answer 25

bilateral and symmetrical

Question 26

cysts in autosomal recessive polycystic kidney disease are seen appearing

Answer 26

from the collecting duct system

Question 27

autosomal recessive polycystic kidney disease is always associated with

Answer 27

hepatic diseased the kidneys are ALWAYS palpable

Question 28

clinical présentation of autosomal recessive polycystic kidney disease is

Answer 28

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

Question 29

acquired cystic kidney disease

Answer 29

is not inherited and usually occurs later on in life

Question 30

acquired cystic kidney disease usually occurs in those

Answer 30

who have underlying kidney problems i.e. it is more common in people with kidney failure or those who are on dialysis

Question 31

alport syndrome is caused by

Answer 31

mutations of type 4 collagen

Question 32

type 4 colagen is important in

Answer 32

- glomerulus of the kidney - eye - cochlea

Question 33

type 4 collagen is found in

Answer 33

all basement membranes

Question 34

basement membrane structure

Answer 34

- lamina lucida - lamina densa - lamina reticularis

Question 35

basement membrane of the glomerulus in alports syndrome becomes

Answer 35

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

Question 36

collectively the haematuria, renal insufficiency and hypertension contribute to the categorisation of aport syndrome as a

Answer 36

glomerulonephritis

Question 37

why is the ear affected in alports syndrome

Answer 37

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

Question 38

type of hearing loss in alport syndrome

Answer 38

sensinoneural

Question 39

alport syndrome can also cause

Answer 39

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

Question 40

type 4 collagen is

Answer 40

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

Question 41

each alpha chain has

Answer 41

a repetitive amino acid sequence

Question 42

most common form of alport syndrom is caused by a mutation of the

Answer 42

COL4A5 gene on the X chromosome which is why it is a form of X linked inheritance

Question 43

alport syndrome can also be caused by a mutation of the

Answer 43

COL 4A3 OF COL4A4 GENE which are present on autosomes and would be inherited autosomal dominantly or autosomal recessively

Question 44

suspect alport syndrome in anyone with

Answer 44

haematuria and hearing loss

Question 45

diagnosis of aport syndrome

Answer 45

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

Question 46

treatment of aport syndrome

Answer 46

aggressive management of proteinuria using ACE inhibitors or angiotensin receptor blockers - will eventually require analysis or renal transplant

Question 47

Anderson Fabrys disease

Answer 47

X linked lysosomal storage disorder which causes a deficiency in the enzyme alpha- galactosidase A

Question 48

anderson fabrys disease affects

Answer 48

the liver, lungs, kidneys and erythrocytes

Question 49

anderson fabrys disease causes a build up of

Answer 49

ceramide trihexoside

Question 50

clinical features of anderson fabrys disease

Answer 50

renal failure, cutaneous angiokeratoma, cardiomyopathy, stroke, acroparaesthesia

Question 51

diagnosis of anderson fabrys disease

Answer 51

enzyme assay measuring the amount of alpha- GAL enzyme

Question 52

treatment of anderson fabrys disease

Answer 52

enzyme replacement using fabryzyme

Question 53

medullary cystic kidney disease inherited

Answer 53

autosomal dominantly

Question 54

medially cystic kidney disease causes

Answer 54

tubuluo-interstitial fibrosis and inflammation, tubular atrophy, cysts in the cortico-medually junction and eventually causes glomerulosclerosis

Question 55

medullary cystic kidney disease is caused by mutation in

Answer 55

MUC1 gene

Question 56

medially cystic kidney disease causes

Answer 56

polyuria ,polydipsia due to inability to concentrate urine, sats wasting eventually causing renal failure

Question 57

treatment of medially cystic kidney disease

Answer 57

renal transplant

Question 58

medullary sponge kidney

Answer 58

medullar of the kidney becomes spongy

Question 59

medullary sponge kidney is inherited

Answer 59

not inherited and occurs sporadically

Question 60

during foetal development

Answer 60

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

Question 61

medullary sponge kidney is thought to be due to

Answer 61

abnormal induction of the metanephring blastema by the ureteric duct causing dilation of the collecting ducts and small cysts forming in the collecting duct

Question 62

medullary spoke kidney does not cause

Answer 62

renal failure

Question 63

medullary sponge kidney causes

Answer 63

nephrolithiasis (renal stones) in the collecting ducts because there is failure of the kidney to re-absorbe and secrete solutes

Question 64

diagnosis of medullary sponge kidney

Answer 64

IV pyelogram