Inherited Renal Disorders Flashcards
2 types of polycystic kidney disease?
autosomal dominant (most common) autosomal recessive
what is ADPKD?
autosomal dominant polycystic kidney disease
most frequent life threatening hereditary disease
what causes ADPKD?
genetic inheritance pattern
mutation on chromosome 16 (polycystic disease 1)
chromosome 4 (PKD 2)
what mutations cause ADPKD?
PKD 1 (Most common) = chromosome 16 PKD 2 (less common) = chromosome 4 having either has prognostic implications
which ADPKD is more severe?
PKD1
patients develop end stage renal failure earlier than PKD2
what happens in ADPKD?
enlargement of the kidneys due to massive cysts
- normal size = 10-12cm
describe cysts in ADPKD
epithelial lined
arise from a population of renal tubules
most are benign (benign adenomas)
- can progress to become malignant in some cases
clinical renal features of ADPKD?
reduced urine concentration ability chronic pain hypertension haematuria - cyst rupture, cystitis, stones cyst infection renal failure
clinical extra-renal features of ADPKD?
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)
how is ADPKD diagnosed?
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)
how does ADPKD affect children?
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
how can ADPKD be distinguished from recessive?
US suggestion of congenital hepatic fibrosis suggests recessive disease
how is ADPKD managed?
control hypertension hydration proteinuria reduction manage cyst haemorrhage/infection - tolvaptan (reduces cyst colume and progression by increasing urination - CA inhibitor)
specific management of ADPKD?
//
why is hydration important in ADPKD?
helps cyst
must drink a lot to compensate for increased urination when taking tolvaptan
what causes ARPKD?
mutation on chromosome 6
features of ARPKD?
young children associated with hepatic lesions bilateral and symmetrical renal involvement normal urinary tract cysts appear from the collecting ducts
how does ARPKD present?
varies depending on renal/liver lesions kidneys always palpable hypertension recurrent UITs slow decline in GFR (less than 1/3 reach dialysis)
prognosis of ARPKD?
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
what is alports syndrome?
hereditary nephritis
X linked mutation of COL4A5 gene causing disorder of type 4 collagen matrix
how does alports manifest?
haematuria proteinuria (seen in later stages) sensorineural deafness ocular defects - anterior lenticonus leiomyomatosis of oesophagus / genitalia (rare)
how is alports diagnosed?
suspect alports in cases of haematuria + hearing loss
variable thickness GMB on renal biopsy (characteristic feature)
how is alports managed?
no specific treatment
standard aggressive treatment of BP, proteinuria etc
dialysis/transplantation = last resort
what is Anderson fabrys disease?
X linked inborn error of glycosphingolipid metabolism due to deficiency of a-galactosidase A
affects kidneys, liver, lungs, erythrocytes
rare
clinical features of Anderson fabrys disease?
renal failure cutaneous = angiokeratomas cardiac = cardiomyopathy, valvular disease neuro = stroke, acroparaesthesia psychiatric features
how is fabrys disease diagnosed?
plasma/leukocyte a-GAL activity
renal biopsy
skin biopsy
how is Anderson fabrys disease managed?
enzyme replacement - fabryzyme
manage complications
what is a medullary cystic kidney?
rare autosomal dominant inherited cystic disease which affects renal tubules leading to fibrosis
how does medullary cystic kidney affect the kidney?
normal/small kidneys
cysts in corticomeduallry junction and medulla
how is medullary cystic kidney diagnosed?
family history
CT showing cysts in corticomedullary junction/medulla
medullary cystic kidney usually presents at what age?
around 28
definitive treatment for medullary cystic kidney?
transplant
what is medullary sponge kidney?
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
how is medullary sponge kidney diagnosed?
excretion urography to demarcate calculi
what is the commonest inherited kidney disease?
ADPKD
