Autosomal recessive polycystic kidney disease typically presents in neonates or infants with massive, bilaterally enlarged kidneys demonstrating microcystic changes and congenital hepatic fibrosis, both due to a mutation in the PKHD1 gene.
Description
ARPKD is a rare but severe genetic disorder characterised by bilateral, diffuse renal cystic changes, hepatic fibrosis, and biliary dysgenesis. It is one of the most critical causes of renal-related morbidity and mortality in children.
Pathogenesis
ARPKD is a ciliopathy that results from mutations in the PKHD1 gene on chromosome 6p21-p23, which encodes fibrocystin, a protein essential for normal tubular development in the kidneys and the structure of the biliary epithelium in the liver.
Subtypes
ARPKD is a monogenic disease, and there are no recognised subtypes.
Epidemiology, Risk Factors & Associations
- Autosomal recessive inheritance, both parents must be carriers (1 in 4 chance with each pregnancy)
- Incidence approximately 1 in 20,000 live births
- Associated with congenital hepatic fibrosis (100% of cases), Caroli disease, pulmonary hypoplasia from Potter sequence in-utero.
Clinical Features
- Prenatal presentation with oligohydramnios and pulmonary hypoplasia (cyanotic and respiratory acidosis)
- Neonatal hypertension and renal failure
- Progression to chronic kidney disease
- Hepatic symptoms due to associated congenital hepatic fibrosis (hepatomegaly, variceal bleeding)
Complications
- Early end-stage renal disease
- Portal hypertension due to associated hepatic fibrosis
- Respiratory distress in neonates due to large kidneys
Pathological Features
Histopathology
- Macroscopic: Bilaterally enlarged kidneys with a smooth outer surface. The liver almost always has cysts and proliferating bile ducts, which leads to congenital hepatic fibrosis.
- Microscopic: Numerous small, elongated cysts extending from the renal cortex to the medulla
Serology
- Genetic testing showing mutation in PKHD1
Biochemistry
- Elevated serum creatinine and urea, indicating renal impairment
Radiological Features
General Features
- Massively enlarged kidneys with poor corticomedullary differentiation and a sponge-like appearance due to numerous small cysts.
- Oligohydramnios.
CT
- Non-contrast: Enlarged, hypodense kidneys with a “sponge-like” appearance
MRI
- T1: Isointense to hypointense kidneys
- T2: Hyperintense kidneys due to numerous small cysts
US
- B-mode: Cysts are typically below the size resolution for sonography. Therefore kidneys appear massively enlarged with increased echogenicity of the pyramids and loss of corticomedullary differentiation. Preserved hypoechoic halo of cortical tissue.
- Colour: Normal renal artery blood flow, but potentially diminished due to renal dysfunction
Diagnosis
Diagnosis is typically made through a combination of clinical features, imaging, and genetic testing.
Differential Diagnosis
- Autosomal Dominant Polycystic Kidney Disease: ADPKD typically presents later in life, cysts are larger, and kidneys are not as massively enlarged. It is caused by mutations of polycystin 1 (majority) and 2 (PKD1 & 2).
- Multicystic dysplastic kidney: Unilateral kidney involvement, non-functioning kidney
- Meckel-Gruber syndrome: Rare and lethal. Occipital encephalocoele, post-axial polydactyly, dysplastic cystic kidneys with resultant oligohydramnios and associated pulmonary hypoplasia.
Management
- No cure, treatment is supportive
- Management of hypertension is crucial
- Dialysis and renal transplantation for end-stage renal disease
- Management of complications related to hepatic fibrosis