Kidney Week

Abstract: SA-PO0581

Genotyping and Phenotyping Early- and Very Early-Onset ADPKD

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

• Evangelou, Eirini, Department of Nephrology, General Hospital of Athens “G. Gennimatas”, Athens, Greece

Eirini Evangelou, MD

• Poulli, Tsielestina, Department of Nephrology, General Hospital of Athens “G. Gennimatas”, Athens, Greece

Tsielestina Poulli, MD, MSc

• Kostopoulou, Myrto, Department of Nephrology, General Hospital of Athens “G. Gennimatas”, Athens, Greece

Myrto Kostopoulou, MD

• Konsta, Maria, Department of Rheumatology, Sismanoglion General Hospital, Athens, Greece

Maria Konsta, MD, PhD

• Varveri, Maria, Department of Nephrology, General Hospital of Athens “G. Gennimatas”, Athens, Greece

Maria Varveri, MD, MSc

• Poula, Aggeliki, Department of Nephrology, General Hospital of Athens “G. Gennimatas”, Athens, Greece

Aggeliki Poula

• Lazaros, Leandros, Genesis Genoma Lab, Genetics Diagnosis, Clinical Genetics & Research, Athens, Greece

Leandros Lazaros, PhD

• Frangou, Eleni A., Aretaieio Hospital, National and Kapodistrian University of Athens Medical School, Athens, Greece

Eleni A. Frangou, MD, MSc, PhD

• Tsirpanlis, George I., Department of Nephrology, General Hospital of Athens “G. Gennimatas”, Athens, Greece

George I. Tsirpanlis, MD, PhD

Background

ADPKD is usually diagnosed in adults. Early (18 months - 15 years) and very early (<18 months) onset (EO and VEO) is rare. This study investigates genetic and phenotypic profiles in a group with EO and VEO patients.

Methods

From a total of 135 patients with genetic analysis, 27 (15 females) were diagnosed early (4 VEO and 23 EO). All patients underwent targeted next-generation sequencing or Sanger sequencing and Multiplex Ligation-Dependent Probe Amplification. Magnetic Resonance Imaging (MRI) was performed in 14 patients at study entry, revealing more than 10 renal cysts. Younger children with and without positive family history (FH) displayed 2-6 cysts on ultrasound.

Results

The median age at diagnosis and at study entry were 4 (IQR: 3-7 years), and 13 years (IQR: 4-17 years) respectively. Twenty one patients had positive FH. The ADPKD parents of 9 patients developed End Stage Kidney Disease (ESKD) at a median age of 43 (42-48) years. Among the 12 remaining patients with positive FH, 6 had parents with an e-GFR lower than expected for their age (<90 ml/min for 40-44, < 75 for 45-49 and <60 for 50-55 years old). At study entry, 46% of the 27 patients had hypertension and among the 14 patients with MRI, 36% were Mayo Clinic Imaging Category 1C, 29% 1D, 14% 1A, 14% 1E and 7% 1B. Their e-GFR was 120 (118-120) ml/min/1.73m² at study entry. The predicted time to ESKD, was 37 (25-42) years. Genetic testing was positive in 26 out of 27 patients. Variants in PKD1 were found in 23/27 and in PKD2 in 2/27 patients. Two patients had 2 pathogenic variants (PKD1 + SLC7A9 and PKD1 + PKHD1). Twenty-one (81%) of the PKD1 variants were truncated (38% nonsense, 31% frameshift, 4% splicing and 8% CNV-large deletions) while 19% were non-truncated (missense, pathogenic and likely pathogenic). Among the 4 VEO ADPKD patients, one had a large deletion (PKD1 exons 25-33del), one a frameshift PKD1 variant, one had double variants (PKD1 + SLC7A9), and one had negative genetic testing.

Conclusion

Truncating pathogenic PKD1 variants, large deletions and double genetic injuries predominate in VEO and EO ADPKD. Family history and phenotype are also emphasized, together forming a distinctive genetic and phenotypic profile that may indicate early ADPKD onset.

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025v9sdqrxg