Autosomal recessive polycystic kidney disease

1. AUTOSOMAL RECESSIVE POLYCYSTIC
KIDNEY DISEASE
(ARPKD)
SUNIL KUMAR.P
Haematology & Transfusion Medicine
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2. • Introduction
• Definition
• Epidemiology
• Etiology – Genetic
• Pathogenesis
• Clinical features
• Morphological features
• Diagnosis
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3. INTRODUCTION
• The infantile (AR) form of polycystic kidney
disease (ARPKD) is distinct from the adult
form.
• ARPKD is less common.
• Incidence : 1:20,000 births.
• It is transmitted as an autosomal recessive
trait & family H/o of similar disease is not
present.
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4. DEFINITION
• ARPKD is the recessive form of PKD. It is
associated with a group of congenital
fibrocystic syndromes. Mutations in the
PKHD1 (chromosomal locus 6p12.2) cause
ARPKD.
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5. Epidemiology:
• Inherited disorder – progressive enlargement
of renal collecting ducts varying degrees of
hepatic abnormality
• Rare 1:10,000 to 1:40,000
• Caucasians > other ethnic groups?
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6. Genetics
• AR
• Mutation in PKHD1, chromosome 6P21
• Encodes for polyductin/fibrocystin protein
• This protein is localised in primary cilia mainly
in the kidney
• To lesser extent in liver, pancrease and arterial
wall.
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7. Pathogenesis
• The condition occurs due to a mutation in
chromosome 6p21, PKHD1 (polycystic kidney
and hepatic disease).
• It is invariably bilateral.
• The age at presentation may be perinatal,
neonatal, infantile or juvenile.
• ….But frequently serious manifestations are
present at birth and result in death from renal
failure in early childhood.
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8. Clinical features:
• Flank masses
• HTN
• Urinary concentration defect
• Hyponatraemia
• Renal insufficiency
• Pulmonary hypoplasia
• Oesophageal varices
• hyperspleenism
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9. Morphologic Features
• Gross Findings :
• The kidneys are bilaterally enlarged with
smooth external surface and reniform shape.
• C/s- reveals small, fusiform or cylindrical cysts
radiating from medulla to cortex.
• Kidneys – sponge like appearance
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10. • Microscopic findings :
• The total No. of nephrons is normal.
• Collecting tubules show cylindrical or saccular
dilatations & are lined by cuboidal to low
columnar epithelium.
• Glomeruli – shows cystically dilated.
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11. Diagnosis
• US features typical of ARPKD(
enlarged,ecchogenic kidneys with poor CMD
and
• clinical, lab or radiological evidence of hepatic
Fibrosis
• hepatic pathology demonstrating ductal plate
abnormality previous affected sibling
• parental consanguinity suggestive of AR
inheritance
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12. • Genetic testing is typically not required for
patient with classic ARPKD
• Prenatal diagnosis in a family with at least one
affected child via mutation analysis
• With identification and cloning of PKHD1
molecular analysis is now available
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