Abstract: FR-PO0911
Utility of Transcriptomics for Pediatric Extrapolation in Autosomal Recessive Polycystic Kidney Disease
Session Information
- Pediatric Nephrology: Genetic Diseases, Development, Neonatal Nephrology, Glomerular Diseases, and More
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pediatric Nephrology
- 1800 Pediatric Nephrology
Authors
- Varma, Vijayalakshmi, AstraZeneca Pharmaceuticals LP, Gaithersburg, Maryland, United States
- Sinsakul, Marvin, AstraZeneca Pharmaceuticals LP, Gaithersburg, Maryland, United States
- Hofherr, Alexis, AstraZeneca Pharmaceuticals LP, Molndal, Gothenburg, Sweden
- Ryaboshapkina, Maria, AstraZeneca Pharmaceuticals LP, Molndal, Gothenburg, Sweden
Background
Children with ARPKD have a rare and life-threatening kidney and liver disease with no approved therapies. Regulatory frameworks for pediatric extrapolation (e.g., ICH E11A) require evidence of similar pathophysiology and outcomes in adults and children, but current guidance does not consider high-dimensional molecular data. We tested whether a transcriptomic analysis of ARPKD can help quantify its similarity to adult conditions to support pediatric extrapolation.
Methods
We identified differentially expressed genes in ARPKD (GSE242476) and used Ingenuity Pathway Analysis (Qiagen) to compare ARPKD’s transcriptomic signature to that of 32 kidney conditions. Diseases with 2-fold higher median similarities to ARPKD than the technical negative control were considered significantly similar (>17%).
Results
ARPKD’s transcriptomic profile resembled adult adult autosomal dominant PKD (ADPKD) kidney cyst tissue (~28% similarity for small cysts; ~18% for medium cysts) and two pediatric kidney tumors (Wilms tumor ~29%; clear cell sarcoma ~24%). Pathway analysis of ARPKD vs. ADPKD (GSE7869) highlighted shared cilia-related proliferative pathways, canonical Wnt signaling, and metabolic defects, while metabolic adaptation and GPCR signaling diverged (Fig. 1).
Conclusion
This case study suggests that an exploratory transcriptomic approach may help identify adult diseases for pediatric extrapolation and clarify which adult disease pathways are recapitulated in children even when pediatric data are limited.
Fig. 1. Molecular dysregulation in pediatric ARPKD due to PKHD1 and adult ADPKD due to PKD1 compared to control kidneys. Computational inference with IPA; p<1e-5 significant, p <0.05 trend.
Funding
- Commercial Support – AstraZeneca