3. POLYCYSTIC KIDNEY DISEASE
PKD
polycystic kidney disease (PKD) is an inherited disorder
characterized by the development of multiple cysts
develop primarily within kidneys, causing kidneys to
enlarge and lose function over time.
•Prev. 1 in 400-1000.
•23 need renal replacement
•60th .. ESRF
7. Autosomal dominant PKD(ADPKD)
• Called adult cystic kidney disease because symptoms manifest in
adulthood, is passed from parent to child by an autosomal
dominant type of inheritance.
• Most common genetic cause of chronic kidney disease
• Renal failure occurs from cysts replacing renal parenchyma over
time.
• As recurrent episodes of pyelonephritis and nephrolithiasis
8. genes of PKD
• Both are component of primary cilium
Polycystine 2
Polycystine 1
PKD2 mutation
• on chromosome
4(15%)
• Less sever
• Later onset
PKD1 mutation
• on chromosome
16(85%)
• More sever
• Earlier onset
9.
10. Clinical features of autosomal
dominant
1. Hematuria
usually visible and thought to be due to rupture of cysts into the
collecting system
2. Abdominal pain(FLANK)
sources include pyelonephritis, stones, and hemorrhaging into
cysts
3.HTN (in >50% of the cases)
Due to compression by cyst on neighboring tubule decrease blood flow =
decrease O2= activation of RAAS system
4. Palpable kidneys on abdominal examination
11. Complications/associated findings
a. Intracerebral berry aneurysm (in 5% to 20% of cases)—most do not
rupture.. if ruptured = subarachnoid hemorrhage ( circle of willis)
b. Infection of renal cysts; bleeding into cysts
c. Renal failure (late in the disease)
d. Kidney stones.
f. Cysts in other organs (liver, spleen, pancreas, brain, seminal vesicle)
g. Diverticula (colon)
h. Hernias (abdominal/inguinal)
i. Heart valve abnormalities (especially mitral valve prolapse)
j. Aortic root dilatation = heart failure
13. Autosomal recessive PKD (ARPKD)
• Called infantile cystic kidney disease because symptoms
manifest in infancy.
• Inherited mutation of both copy of gene , This means that both
parents must carry the abnormal gene, and both must pass the
gene to the child in order for the Child to develop the disease.
• The less common form of PKD.
14. gene mutation
PKHD1 mutation
On chromosome 6
Fibrocystin
Co localizes with
polycystine Modulates
RenalTubular Formation
by Regulating Polycystin-2
Expression and Function
15. features of autosomal recessive
Potter syndrome
is a developmental abnormality characterized by
pulmonary hypoplasia
oligohydramnios
twisted face
twisted sKin
extremity defects(club feet)
Renal failure (in utero)
with severe ARPKD Possible renal failure before birth →decrease urine
production → low amniotic fluid (oligohydramnios) Lead to:
16. Liver involvement is always present, and may be the dominant clinical
feature, especially in older individuals. Hepatic complications include:
- congenital hepatic fibrosis
• -portal HTN can lead compromised blood flow to porto-renal system
1. Esophageal varices
2. Upper GI bleeding
3. Splenomegaly
4. Hemorrhoids
5. cholangitis.
17. Pulmonary insufficiency secondary to pulmonary hypoplasia and enlarged
kidneys limiting diaphragmatic movement may be severe. Pulmonary
complications are the leading cause of morbidity and mortality in the
neonatal period.
Kidneys are increased in size which may cause severe abdominal distension.
HTN
Hematuria
Flank pain
18.
19. Diagnosis of ARPKD
1. detected prenatally due to the widespread use of ultrasound
during pregnancy.
2. Oligohydramnios during pregnancy usually indicates severe
disease.
3. Ultrasound will show characteristic renal cysts. Ultrasound will
also show hepatomegaly and dilated bile ducts
4. Molecular genetic testing may confirm the disease in cases
where the diagnosis is unclear.
