Kidney Week

Abstract: SA-PO0100

Genetic Variant Analysis and Correlation with Clinical Parameters in 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

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

Danai Palaiologou, MSc, PhD

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

Leandros Lazaros, PhD

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

Paraskevi Karanikola

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

George I. Tsirpanlis, MD, PhD

Background

Genotype-phenotype correlations are clinically important in ADPKD. This study evaluated genetic profiles and their associations with clinical and laboratory parameters in a large cohort.

Methods

Patients attending the ADPKD outpatient clinic at our hospital were included. Demographic, clinical, laboratory, imaging, and genetic data were collected. Genetic testing included targeted next-generation or Sanger sequencing and Multiplex Ligation-Dependent Probe Amplification. MRI data were analyzed when available.

Results

A total of 163 patients (81 females; median age at diagnosis: 23 years) were included. Genetic analysis confirmed the diagnosis in 153 (94%). Variants in PKD1 were detected in 119 (73%), in PKD2 in 21 (13%), and in other genes in 13 (8%). 71.5% of PKD1 variants were truncating and 28.5% non-truncating (Figure 1). Mean age at diagnosis was 21 years in PKD1, 29 years in PKD2 and 34 years in patients with other genes (p<0.001). Hypertension was diagnosed at a mean age of 30, 40, and 55 years, respectively (p<0.001). In patients with a positive family history, age at end-stage kidney disease in first-degree relatives was 52, 65 and 58 years old, respectively (p<0.003). No significant differences were observed between truncating and non-truncating PKD1 variants. Among 28 patients with missense PKD1 variants, 19 had variants located in specific PKD1 gene domains (Plat, REJ, C-type lectin and PKD). Sensitivity analysis showed that, after exclusion of these variants, PKD1 truncating patients were diagnosed 7.6 years earlier than non-truncating patients (coef. -7.64 (SE 3.28), p=0.02). Higher total kidney volume (TKV) was observed in frameshift PKD1 variants (2052, 1138,1017,1656 ml for frameshift, nonsense, splicing, intronic variants, respectively; p<0.001).

Conclusion

ADPKD-PKD1 patients exhibit a more severe clinical phenotype. Non-truncating PKD1 missense variants located in specific domains may be associated with more rapid disease progression. Among truncating variants, frameshift mutations may be linked to more aggressive disease, as reflected by higher TKV.