Clinical and Genetic Epidemiology of Autosomal Dominant Polycystic Kidney Disease among patients incident on first kidney replacement therapy between 1990-2023, in a major hospital in the Northwest of Portugal

Introduction. Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic kidney disease, accounting for 5–10% of incident patients requiring kidney replacement therapy (KRT). Although most cases result from pathogenic variants in PKD1 (≈75%) or PKD2 (≈15%), clinical experience at a major academic hospital in Porto (ULSSJ), suggested a higher regional prevalence of ADPKD-PKD2, particularly involving the truncating variant PKD2 p.(Gln61*). This study aimed to characterize the clinical and genetic epidemiology of ADPKD in patients initiating KRT at ULSSJ, compare ADPKD-PKD1 with ADPKD-PKD2, and contrast local and national ADPKD prevalence among incident KRT patients. Methods. Nephrology reports for KRT initiation (NR-KRT) issued at ULSSJ from 1990 to 2023 were reviewed to identify ADPKD cases and extract demographic and clinical data. Genotypes were obtained from the Genetics Laboratory, Faculty of Medicine, University of Porto, or inferred through pedigree analysis. Next-generation sequencing was the first-tier genotyping test, with Sanger sequencing and multiplex ligation-dependent probe amplification for unresolved cases. National prevalence figures for ADPKD among incident KRT were retrieved from the Portuguese Society of Nephrology registry. Results. Among 6791 NR-KRT reviewed, 426 ADPKD patients were identified. Genotyping information was available for 168 individuals (39.4%), including 101 (60.1%) with inferred genotypes. Among genetically resolved cases, 70.2% had ADPKD-PKD1 and 29.8% had ADPKD-PKD2. Mean age at KRT initiation was 54.5 years in ADPKD-PKD1 and 66.9 years in ADPKD-PKD2. The PKD2 p.(Gln61*) variant was present in 39 patients (23.2%). Between 2010 and 2023, ADPKD prevalence among incident KRT patients was 7.48% at ULSSJ versus 5.19% nationwide (p<0.0001). Conclusion. The prevalence of ADPKD among incident KRT patients at ULSSJ exceeded national rates. ADPKD-PKD1 was associated with earlier kidney failure compared to ADPKD-PKD2. PKD2 p.(Gln61*) variant was the most frequent pathogenic allele identified. Given historical patterns of Portuguese emigration, these findings likely have broader international clinical relevance.