Inherited Renal Disorders

Question 1

2 types of polycystic kidney disease?

Answer 1

autosomal dominant (most common)
autosomal recessive

Question 2

what is ADPKD?

Answer 2

autosomal dominant polycystic kidney disease

most frequent life threatening hereditary disease

Question 3

what causes ADPKD?

Answer 3

genetic inheritance pattern
mutation on chromosome 16 (polycystic disease 1)
chromosome 4 (PKD 2)

Question 4

what mutations cause ADPKD?

Answer 4

PKD 1 (Most common) = chromosome 16
PKD 2 (less common) = chromosome 4
having either has prognostic implications

Question 5

which ADPKD is more severe?

Answer 5

PKD1

patients develop end stage renal failure earlier than PKD2

Question 6

what happens in ADPKD?

Answer 6

enlargement of the kidneys due to massive cysts

- normal size = 10-12cm

Question 7

describe cysts in ADPKD

Answer 7

epithelial lined
arise from a population of renal tubules
most are benign (benign adenomas)
- can progress to become malignant in some cases

Question 8

clinical renal features of ADPKD?

Answer 8

reduced urine concentration ability
chronic pain
hypertension
haematuria - cyst rupture, cystitis, stones
cyst infection
renal failure

Question 9

clinical extra-renal features of ADPKD?

Answer 9

hepatic cysts (most common)
- often presents 10 yrs after renal cysts
- generally doesn’t affect liver function
- can cause SOB, pain, ascites, ankle swelling
intra-cranial aneurysms (not common)
- usually in anterior circulation (e.g cerebral)
- familial
cardiac disease (valve disease)
diverticular disease
hernias (abdo/inguinal)

Question 10

how is ADPKD diagnosed?

Answer 10

clinical and family history
imaging
- US = multiple bilateral cysts, renal enlargement
- CT/MRI - only if unclear on US
- calcification of cysts can sometimes be seen on X ray
genetic testing (linkage/mutation analysis)

Question 11

how does ADPKD affect children?

Answer 11

early onset can be in first year of life
siblings at increased risk of early disease
renal involvement same as adults, however cerebral aneurysms are rare
single cyst often enough for diagnosis

Question 12

how can ADPKD be distinguished from recessive?

Answer 12

US suggestion of congenital hepatic fibrosis suggests recessive disease

Question 13

how is ADPKD managed?

Answer 13

control hypertension
hydration
proteinuria reduction
manage cyst haemorrhage/infection 
- tolvaptan (reduces cyst colume and progression by increasing urination - CA inhibitor)

Question 14

specific management of ADPKD?

Answer 14

//

Question 15

why is hydration important in ADPKD?

Answer 15

helps cyst

must drink a lot to compensate for increased urination when taking tolvaptan

Question 16

what causes ARPKD?

Answer 16

mutation on chromosome 6

Question 17

features of ARPKD?

Answer 17

young children
associated with hepatic lesions
bilateral and symmetrical renal involvement
normal urinary tract
cysts appear from the collecting ducts

Question 18

how does ARPKD present?

Answer 18

varies depending on renal/liver lesions
kidneys always palpable
hypertension
recurrent UITs
slow decline in GFR (less than 1/3 reach dialysis)

Question 19

prognosis of ARPKD?

Answer 19

30-50% of kids are severely affected
infants who survive neonatal period have 9-24% mortality rate in first year of life
80% survival beyond 15 yrs if child survives first year of life

Question 20

what is alports syndrome?

Answer 20

hereditary nephritis

X linked mutation of COL4A5 gene causing disorder of type 4 collagen matrix

Question 21

how does alports manifest?

Answer 21

haematuria
proteinuria (seen in later stages)
sensorineural deafness
ocular defects - anterior lenticonus
leiomyomatosis of oesophagus / genitalia (rare)

Question 22

how is alports diagnosed?

Answer 22

suspect alports in cases of haematuria + hearing loss

variable thickness GMB on renal biopsy (characteristic feature)

Question 23

how is alports managed?

Answer 23

no specific treatment
standard aggressive treatment of BP, proteinuria etc
dialysis/transplantation = last resort

Question 24

what is Anderson fabrys disease?

Answer 24

X linked inborn error of glycosphingolipid metabolism due to deficiency of a-galactosidase A
affects kidneys, liver, lungs, erythrocytes
rare

Question 25

clinical features of Anderson fabrys disease?

Answer 25

renal failure
cutaneous = angiokeratomas
cardiac = cardiomyopathy, valvular disease
neuro = stroke, acroparaesthesia 
psychiatric features

Question 26

how is fabrys disease diagnosed?

Answer 26

plasma/leukocyte a-GAL activity
renal biopsy
skin biopsy

Question 27

how is Anderson fabrys disease managed?

Answer 27

enzyme replacement - fabryzyme

manage complications

Question 28

what is a medullary cystic kidney?

Answer 28

rare autosomal dominant inherited cystic disease which affects renal tubules leading to fibrosis

Question 29

how does medullary cystic kidney affect the kidney?

Answer 29

normal/small kidneys

cysts in corticomeduallry junction and medulla

Question 30

how is medullary cystic kidney diagnosed?

Answer 30

family history

CT showing cysts in corticomedullary junction/medulla

Question 31

medullary cystic kidney usually presents at what age?

Answer 31

around 28

Question 32

definitive treatment for medullary cystic kidney?

Answer 32

transplant

Question 33

what is medullary sponge kidney?

Answer 33

sporadic inheritance of disease causing dilation of collecting ducts
- can cause medullary area to appear like a sponge in severe cases
also causes formation of calculi in cysts
usually doesn’t cause renal failure
uncommon

Question 34

how is medullary sponge kidney diagnosed?

Answer 34

excretion urography to demarcate calculi

Question 35

what is the commonest inherited kidney disease?

Answer 35

ADPKD