#1040 Correlation of genotype to disease onset age and hypertension diagnosis in autosomal dominant polycystic kidney disease

Abstract

Abstract Background and Aims Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the predominant genetic disease leading to End Stage Kidney Disease (ESKD). Genetic identity could correlate to the disease profile. Correlations between genetic and phenotype characteristics in a cohort of ADPKD patients are investigated. Method Genetic analysis was conducted in 85 patients with an ADPKD phenotype, employing targeted Next Generation (tNGS) or Sanger Sequencing and Multiplex ligation-dependent probe amplification (MLPA). Medical history, clinical and laboratory data, including Renal Magnetic Resonance Imaging (MRI) for Total Kidney Volume (TKV) measurement (in 66 patients), were recorded and subsequently correlated to the respective genotypes. Results Eighty-five patients (43 females, 42 males, 33 ± 16 years old) were included in the study. The mean age at diagnosis of the disease was at 21.5 ± 13 (0.6-69) years. Fifty-eight out of 85 patients (68%) had a familial history of ADPKD. The mean age at which the affected parent reached ESKD was 53.0 ± 9 years. Hypertension was diagnosed in 60 individuals (71%) within the study cohort. The mean age at hypertension diagnosis was 31 ± 11 years. In the assessment based on height-adjusted TKV and age, the 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 mutations and 39% non-truncating mutations, while PKD2 mutations were identified in 15 patients (18%). The average age of ADPKD diagnosis differed 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 mutations 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 hypertension 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, the renal survival within families and the hypertension onset. Patients with PKD1-truncating mutations manifest an earlier onset of both the disease and hypertension compared to those with PKD2 gene mutations.