Clinical manifestations of autosomal recessive polycystic kidney disease

Area of Science:

• Genetics and Molecular Biology
• Pediatric Nephrology
• Hepatology

Background:

• Autosomal recessive polycystic kidney disease (ARPKD) is a genetic disorder.
• Mutations in the PKHD1 gene cause ARPKD.
• The disease involves kidney and liver manifestations, now termed hepatorenal fibrocystic disorder or ARPKD-congenital hepatic fibrosis (CHF).

Purpose of the Study:

• To review recent advancements in understanding ARPKD's clinical manifestations.
• To highlight the impact of genetic discoveries on disease classification.
• To emphasize the importance of updated nomenclature reflecting genetic and phenotypic complexity.

Main Methods:

• Review of current literature on PKHD1 gene mutations.
• Analysis of genotype-phenotype correlations (or lack thereof).
• Description of clinical outcomes and management strategies for ARPKD.

Main Results:

• Over 300 PKHD1 mutations identified, but no clear genotype-phenotype correlation.
• Variable kidney cystic phenotype; renal oligohydramnios can be lethal.
• Pulmonary hypoplasia affects neonates; 60% require renal replacement therapy by age 10.
• Liver fibrosis and cholangiodysplasia are common; 10% may need liver transplantation.
• Neurocognitive development generally aligns with moderate renal failure, warranting further study.

Conclusions:

• ARPKD-CHF presents with diverse organ manifestations.
• Multidisciplinary management is essential for anticipating complications.
• Proactive care can potentially improve patient prognosis.