Kidney Week

Abstract: SA-PO0099

Genotype and Phenotype Profile of Early-Onset and De Novo ADPKD

Session Information

• ADPKD and Cystic Kidney Disease - 3
  October 24, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1201 Genetic Diseases of the Kidneys: Cystic (Monogenic)

Authors

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

Eirini Evangelou, MD, PhD

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

Tsielestina Poulli, MD, MSc

• 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

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

Myrto Kostopoulou, MD

• Karanikola, Paraskevi, Department of Nephrology, General Hospital of Athens "G. Gennimatas", Athens, Greece

Paraskevi Karanikola

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

Leandros Lazaros, PhD

• Palaiologou, Danai, Genesis Genoma Lab, Genetics Diagnosis, Clinical Genetics & Research, Athens, Greece

Danai Palaiologou, MSc, PhD

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

George I. Tsirpanlis, MD, PhD

Background

ADPKD typically affects adults with a positive family history, whereas early-onset (EO) disease and absence of familial history are less common. Investigating phenotypic and genetic features in a large cohort of ADPKD patients may provide valuable insights into these distinctive subgroups.

Methods

Patients attending the ADPKD outpatient clinic at our hospital were included. Demographic, clinical, laboratory, imaging, and genetic data were collected. Patients were classified by (1) age at diagnosis (EO <15 years vs non-EO ≥15 years) and (2) family history (positive vs negative/de novo). All patients underwent genetic testing including targeted next-generation sequencing or Sanger sequencing and Multiplex Ligation-Dependent Probe Amplification. MRI data were collected when available. Statistical analysis was performed using Stata 13.0.

Results

Among 163 patients, 74 had non-EO disease with a positive family history, 36 (22%) had EO disease, and 53 (32.7%) were de novo cases. PKD1 variants were more frequent in EO patients (33 PKD1, 2 PKD2, 0 other genes) compared to non-EO patients (86, 19, 13, respectively; p=0.06). No significant differences were observed between EO and non-EO groups regarding truncating versus non-truncating PKD1 variants, nor among nonsense, frameshift, splicing, CNV, intronic versus missense and non-frameshift variants (p=0.50 and p=0.34, respectively). EO patients had earlier hypertension onset than non-EO patients (17.7±7.5 vs 35.5±11.4 years, p<0.001), younger age at enrollment (14.8±11.3 vs 41.5±11.8), higher eGFR (113.5±21.1 vs 73.8±34.4 ml/min), and lower height-adjusted total kidney volume (hTKV) (457.2±371.7 vs 780.7±748.0 ml/m; p<0.001 for both). De novo cases also showed a higher frequency of PKD1 variants compared to positive family history patients (39, 2, 4 vs 78, 19, 9 in PKD1, PKD2, other genes; p=0.02). Neither truncating vs non-truncating nor the aforementioned variants differed between de novo and positive family history patients (p=0.76, p=0.99). De novo patients tended toward higher hTKV (861.7±854.9 vs 640.0±567.6 ml/m; p=0.08) and shorter predicted time to end-stage kidney disease (24.7±16.5 vs 33.8±34.2 years; p=0.09).

Conclusion

PKD1 variants predominate in EO and de novo ADPKD cases. While no major genetic differences were observed beyond this, these subgroups exhibit distinct phenotypic trends, possibly attributed to their PKD1 genetic pattern.