Abstract: TH-PO478
Correlation of Genotype with Age at Disease Onset and Hypertension Diagnosis in Autosomal Dominant Polycystic Kidney Disease
Session Information
- Cystic Kidney Diseases: Clinical Assessment and Therapeutic Directions
October 24, 2024 | 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: Cystic
Authors
- Gkalitsiou, Dimitra, General Hospital of Athens Georgios Gennimatas, Nephrology Department, Athens, Greece
- Evangelou, Eirini, General Hospital of Athens Georgios Gennimatas, Nephrology Department, Athens, Greece
- Konsta, Maria, Department of Rheumatology, Sismanoglion General Hospital, Athens, Greece
- Vasiliou, Kiriaki, General Hospital of Athens Georgios Gennimatas, Nephrology Department, Athens, Greece
- Poula, Aggeliki, General Hospital of Athens Georgios Gennimatas, Nephrology Department, Athens, Greece
- Markou, Niki, General Hospital of Athens Georgios Gennimatas, Nephrology Department, Athens, Greece
- Poulli, Tsielestina, General Hospital of Athens Georgios Gennimatas, Nephrology Department, Athens, Greece
- Palaiologou, Danai, Genesis Genoma Lab, Genetics Diagnosis, Clinical Genetics & Research, Athens, Greece
- Kanellopoulou, Konstantina, General Hospital of Athens Georgios Gennimatas, Nephrology Department, Athens, Greece
- Tsirpanlis, George I., General Hospital of Athens Georgios Gennimatas, Nephrology Department, Athens, Greece
Background
Autosomal Dominant Polycystic Kidney Disease is the predominant genetic disease leading to End Stage Kidney Disease. Genetic identity could correlate to disease profile. Correlations between genetic and phenotypic characteristics in a cohort of ADPKD patients are investigated.
Methods
Genetic analysis was conducted in 85 ADPKD patients, using targeted Next Generation (tNGS) or Sanger Sequencing and Multiplex ligation-dependent probe amplification (MLPA). Medical history, clinical and laboratory data, including MRI for Total Kidney Volume (TKV) measurement, were recorded and subsequently correlated to the respective genotypes.
Results
Eighty-five patients (43 females, 42 males, 33±16 years old) were included. The mean age at diagnosis was 21.5±13 (0.6-69) years. Familial history of ADPKD was present in 58 patients (68%). The mean age at which the affected parent reached ESKD was 53.0±9 years. Hypertension was diagnosed in 60 patients (71%) within the study cohort. The mean age at HTN diagnosis was 31±11 years. In the assessment based on height-adjusted TKV and age, Mayo Clinic Imaging Categories revealed that 9% of patients were classified as 1A, 20% as 1B, 29% as 1C, 29% as 1D, and 13% as 1E. Mutations in PKD1 gene were detected in 70 patients (82%), with 61% exhibiting truncating and 39% non-truncating mutations, while PKD2 mutations were identified in 15 patients (18%). The average age of ADPKD diagnosis varied among genetic subgroups. Patients carrying PKD1-truncating mutations were diagnosed at 17.6±11 years, those with PKD1-non-truncating mutations at 24.5±12 years, and those with PKD2 at 27.3±16 years (p = 0.01). Moreover, the mean age at which the affected parent reached ESKD was 50±8 years, 55±10 and 60±7 years in PKD1-truncating, PKD1-non-truncating and PKD2 patients respectively (p = 0.04). Additionally, the mean age of HTN diagnosis was 29±12 years in PKD1-truncating, 30±10 years in PKD1-non-truncating and 40±7 years in PKD2 patients (p = 0.05).
Conclusion
Mutation type correlates with the age of ADPKD diagnosis, renal survival within families and hypertension onset. Patients with PKD1-truncating mutations manifest an earlier onset of both disease and hypertension compared to those with PKD2 mutations.