Inherited Renal Disorders Flashcards
What is the most common inherited kidney disorder?
Autosomal dominant polycystic kidney disease
What characterises ADPKD?
Development of multiple renal cysts. It is variably associated with extra renal (mainly hepatic and cardiac) abnormalities.
ADPKD is due to mutations in _________
PKD1 (more common) or PKD2 (less common) genes which encode for polycystic proteins
What happens to the kidneys in ADPKD?
The kidneys are converted into a mass of cysts with loss of renal parenchyma. There is cyst formation in some of the collecting tubules causing a mixture of normal and abnormal nephrons. The changes occur after birth and the disease is progressive resulting in atrophy of the normal nephrons by pressure.
What are some renal features of ADPKD? When do symptoms usually present?
From 20s onwards
- reduced urine concentration ability
- chronic pain (in loin)
- hypertension in younger person av age = 31yo
- haematuria due to cyst rupture, cystitis or stones
- cyst infection
- renal failure > signs of CKD e.g. anaemia and uraemia
- can be asymptomatic however and be picked up due to abnormal renal function on tests or due to family screening
What are some extra renal manifestations of ADPKD?
- hepatic cysts (10 yrs after renal cysts) liver function generally preserved by may get SOB, pain, ankle swelling due to compression of surrounding structures
- intracranial aneurysms in 4-8% may need screening if a strong family history
- Cardiac disease > mitral or aortic valve prolapse due to myxomatous degeneration (valve becomes thickened due to formation of small nodules resulting in incomplete closure)
- increased risk of diverticular disease and hernias
What is the most common extra renal manifestation of ADPKD?
Hepatic cysts
Describe how might come to diagnosis of ADPKD?
FH
On exam: large palpable kidneys, potentially hepatomegaly and splenomegaly. Hypertension
On US presence of bilateral renal cysts. CT or MRI can be done if US unclear.
Genetics- Linkage and mutation analysis
Describe management of ADPKD?
Hypertension is managed with ACEi first line
Hydration- increased fluid to reduce vasopressin levels
Tolvapatan is a vasopressin inhibitor. Idea is to reduce cAMP which reduces cyst growth
Treat any cyst infection or haemorrhages
Renal failure treated conventionally with dialysis then transplant
Describe ADPKD in children?
Early onset but with renal onset similar to adults
It is difficult to distinguish from ARPKD. USS suggesting congenital hepatic fibrosis suggests recessive disease.
When distinguishing between ADPKD and ARPKD in children what suggests recessive?
USS suggestive of congenital hepatic fibrosis
Compare the cysts in ADPKD vs ARPKD?
Dominant is spherical cysts at multiple levels
Recessive is fusiform dilation of the renal collecting duct running perpendicular to the capsule. Renal involvement is therefore bilateral and symmetrical.
Describe presentation of ARPKD?
Varies depending on severity (need to distinguish if chance of survival) Kidneys are always palpable in children Hypertension Recurrent UTIs There is a slow decline in GFR
When does ARPKD tend to present?
Presents at birth in utero occasionally in childhood.
What is the prognosis of autosomal recessive PKD?
In severe disease death occurs shortly after birth/ In children who survive infancy congenital hepatic fibrosis often dominates. Children who survive the 1st year have survival of 80% beyond 15yrs.
Basically if do well in first decade they will do better than ADPKD
