Exploring the clinical and genetical spectrum of ADPKD in Chile to assess ProPKD score as a risk prediction tool

Abstract
Background Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited condition associated primarily with PKD1 and PKD2 genes. However, ADPKD patients in Latin America have had limited access to comprehensive care. The ProPKD score predicts the likelihood of kidney failure before the age of 60. This study aimed to describe the clinical and genetic characteristics of Chilean ADPKD patients and assess the ProPKD score. Methods We enrolled 40 ADPKD probands and 122 relatives from different centers. Genetic analysis of PKD1 and PKD2 genes was performed by combining direct and next-generation sequencing. Pathogenicity was determined using bioinformatic tools. ProPKD scores were calculated based on clinical and genetic data. Results ADPKD probands were diagnosed at a median age of 35 years. Pathogenic, likely pathogenic, or uncertain significance variants were identified in 38/40 pedigrees, with 89% involving PKD1 and 11% involving PKD2 variants. Among the identified variants, 62% were novel. Patients with PKD1 truncating variants had a more severe disease course, reaching kidney failure by a median age of 48.5 years. ProPKD scores were assessed in 72 individuals, stratifying them into high-, intermediate-, or low-risk categories and the median ages for kidney failure were 45, 49, and 52 years, respectively (log-rank p = 0.001). Conclusion This study provides valuable insights into the clinical and genetic profiles of ADPKD patients in Chile. ADPKD poses a significant public health concern, warranting improvements in diagnosis and treatment. The use of the ProPKD score to predict disease progression should be further explored to enhance patient care and management.
Description
Keywords
ADPKD, Genetic analysis, End-stage renal disease, ProPKD score
Citation