Kidney Week

Abstract: SA-PO0588

Monogenic Etiologies of Pediatric PKD: A Prospective Study

Session Information

• Cystic Kidney Diseases: Clinical Research
  November 08, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1201 Genetic Diseases of the Kidneys: Monogenic Kidney Diseases

Authors

• Bozkurt, Elif G, Mayo Clinic Minnesota, Rochester, Minnesota, United States

Elif G Bozkurt, MD

• Sheikh Najeeb, Mohamad, Mayo Clinic Minnesota, Rochester, Minnesota, United States

Mohamad Sheikh Najeeb, MD

• Kemppainen, Jennifer L., Mayo Clinic Minnesota, Rochester, Minnesota, United States

Jennifer L. Kemppainen, MS

• Yang, Hana, Mayo Clinic Minnesota, Rochester, Minnesota, United States

Hana Yang, PhD

• Gregory, Adriana, Mayo Clinic Minnesota, Rochester, Minnesota, United States

Adriana Gregory, MS

• Cruz, Conrad, Mayo Clinic Minnesota, Rochester, Minnesota, United States

Conrad Cruz

• Baker, Tracy A., Mayo Clinic Minnesota, Rochester, Minnesota, United States

Tracy A. Baker

• Pinto e Vairo, Filippo, Mayo Clinic Minnesota, Rochester, Minnesota, United States

Filippo Pinto e Vairo, MD, PhD

• Harris, Peter C., Mayo Clinic Minnesota, Rochester, Minnesota, United States

Peter C. Harris, PhD

• Hanna, Christian, Mayo Clinic Minnesota, Rochester, Minnesota, United States

Christian Hanna, MD, MS, FASN

Background

Pediatric polycystic kidney disease (PKD) and ciliopathies show significant genetic diversity. ADPKD in children is typically linked to PKD1 and PKD2, however emerging adult data suggest a broader spectrum. This study assesses next-generation sequencing (NGS) to enhance diagnostic accuracy in pediatric PKD.

Methods

This prospective cohort study (Jan 2020 to Jun 2024), included patients (pts) with ≥2 kidney cysts regardless of laterality and without a PKD family history, or ≥1 cyst with a confirmed PKD family history; pts with multicystic dysplastic kidneys were excluded. Data were obtained from medical records, and genetic testing was done using NGS PKD panels or custom curated kidney gene exome/genome panels, with family segregation analysis when available.

Results

We evaluated 109 children (53% female, median age 7.6 years) from 99 families. Genetic testing was completed for 101 pts from 92 families, identifying pathogenic or likely pathogenic variants in 82 pts (81%) and 73 families (79%). Positive PKD family history and younger age of diagnosis were significantly higher in the genetically resolved group (P<0.05). Gene-specific variant frequencies identified among genetically resolved families are shown in Figure 1A. ADPKD genes accounted for 66% of the total, with PKD1 the most common (45%), but 4 minor ADPKD genes represented 10 families (14%). Eight percent of families were likely ARPKD-PKHD1, but HNF1B/17q12del accounted for a larger proportion (13%). Recessive, syndromic ciliopathies were responsible for just 5% of the resolved families. Pts’ initial presentations were classified into four categories: clinical symptoms, incidental finding, prenatal US detection, and family screening, and the variants detected for each category are shown in Figure 1B, with clinical symptoms the most genetically diverse.

Conclusion

NGS-based testing offers a high and diverse diagnostic yield in pediatric PKD, revealing genetic causes of ADPKD beyond PKD1/PKD2. Broad testing is essential to obtain an accurate diagnosis, informing prognosis, and guide personalized care

Funding

• NIDDK Support

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.20254pb8h9ct