ERKNET Webinar on Autosomal Recessive Polycystic Kidney Disease

May 29, 2024

Review flashcards

EarthNet Webinar on Autosomal Recessive Polycystic Kidney Disease (ARPKD)

Introduction

  • Presenter: Francesco Emma from Rome
  • Speaker: Maxine Bill, a pediatric nephrologist and cell biologist
  • Topic: Autosomal Recessive Polycystic Kidney Disease (ARPKD)
  • Format: 30-minute lecture followed by a 15-minute Q&A session
  • Audience can submit questions via the GoToWebinar application
  • Presenter Background: Head of experimental pediatric nephrology and the interdisciplinary center for chronically healed children at the University Hospital of Cologne

Overview of ARPKD

  • Definition: Genetic disorder, autosomal recessive
  • Main Genetic Cause: Variants in the PKHD1 gene
  • Recent Discovery: Variants in another gene, DZIP1L
  • Protein Involved: Fibrocystein, function poorly understood
  • Clinical Features: Massively enlarged kidneys due to dilation of the collecting ducts; obligatory hepatic involvement (ductal plate malformation, hepatic fibrosis, portal hypertension)

Diagnosis and Imaging

  • Characteristics: Enlarged kidneys, typical ā€œsalt and pepperā€ sign on ultrasound
  • Histology: Ubiquitous microcysts in the kidney
  • Clinical Criteria: Combination of kidney and hepatic imaging findings, autosomal recessive pattern of inheritance
  • Genetic Testing: Important for differentiating ARPKD from phenocopies

Clinical Course and Management

  • Survival Rates: Neonatal survival up to 90%; post-neonatal survival relatively good
  • Cause of Early Death: Pulmonary hypoplasia, sepsis, chronic kidney disease (CKD)
  • Renal Survival: About 50% renal survival by age 20, but highly variable
  • Risk Factors for Early Dialysis Dependency: Oligo/anhydramnios, prenatal enlarged kidneys, low Apgar score
  • Predictive Model: Stratified risk pattern for early dialysis dependency

Treatment Approaches

  • Current Treatments: Mainly symptomatic treatment
  • Management: Plan delivery in well-equipped NICU, use peritoneal dialysis (PD) for neonates, manage hypertension with multiple agents, careful monitoring of sodium levels
  • Nephrectomy: Unilateral nephrectomy lacks evidence for respiratory improvement or hypertension management; early bilateral nephrectomies associated with severe neurological complications
  • PD Feasibility: PD can be used effectively in young children with ARPKD

Genetic and Observational Studies

  • Registry Data: ARPKD Registry (A-REG) with over 600 patients from 30 countries
  • Findings: Large dataset enables longitudinal studies and better understanding of clinical courses

Key Points and Recommendations

  • Key Messages: ARPKD remains a clinical challenge; genetic testing aids in diagnosis; treatment remains symptomatic; need for international research collaboration
  • Registries: Essential for collecting data and improving understanding of ARPKD
  • Upcoming Webinars: Next webinars focus on chronic hemodialysis access and systemic amyloidosis

Q&A Session Highlights

  • Nephrectomy & Hypertension: No specific treatment for severe hypertension post-nephrectomy; sodium management is critical
  • Genotype-Phenotype Correlation: General expectation of severe phenotypes with truncating mutations, but exceptions exist
  • Prenatal Counseling: Difficulty in predicting clinical outcomes; importance of providing comprehensive information to families
  • Perinatal Management: Amnioinfusion data unclear on efficacy, needs more study

References

  • Consulted Studies: Work by Mayo Clinic, Lisa K. Woodford, Larissa Karachukā€™s Renal Radar, and ARPKD Registry data from University Hospital of Cologne

Conclusion

  • ARPKD is a complex and variable disease requiring careful, multidisciplinary management and continuing research efforts.
  • Emphasis on collaborative international research to develop targeted therapies and improve patient outcomes.