Screening for genetic kidney diseases in a dialysis cohort via exome sequencing.

Background: Monogenic causes are increasingly recognized in end-stage kidney disease (ESKD), but the real-world diagnostic efficacy of exome sequencing in unselected dialysis cohorts is still being defined. Methods: We conducted a prospective study enrolling 317 adult ESKD patients from a single center in Taiyuan, China, regardless of presumed etiology. Whole-exome sequencing (WES) was performed on peripheral blood DNA. Variants were curated and classified per the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) 2015 and Association for Clinical Genomic Science (ACGS) guidelines, with only "pathogenic" or "likely pathogenic" findings considered diagnostic. Results: The cohort was 59% male, mean ESKD onset 53.2 ± 14.3 years. A definitive monogenic diagnosis emerged in 7.3% (23/317) of patients, in line with multicenter and international studies. Genes most frequently implicated were Conclusions: In a real-world Chinese dialysis cohort, WES provided a molecular diagnosis in 7.3% of cases, demonstrating clinical utility for risk stratification, family counseling, donor selection and actionable therapy. These findings underscore the need for routine integration of genetic testing in ESKD care irrespective of family history, especially to clarify ambiguous cases and optimize management.