Background
The growing body of research on kidney disease in children has identified a broad spectrum of genetic etiologies.
Conclusions
Genetic diagnosis provides critical insights into the pathogenesis of kidney disease, optimizes clinical strategies concerning risk assessment of living donors, and enhances disease surveillance of recipients.
Methods
We conducted a prospective study to evaluate the efficacy of an optimized genetic test and subclinical changes in a real-world context before kidney transplantation. All cases involved recipients under the age of 18 who underwent whole exome sequencing (ES) between 2013 and 2022.
Results
The study population included 244 children, with a median age of 13.1 years at transplantation. ES provided a molecular genetic diagnosis in 114 (46.7%) probands with monogenic variants in 15 known disease-causing genes. ES confirmed the suspected clinical diagnosis in 74/244 (30.3%) cases and revised the pre-exome clinical diagnoses in 40/244 (16.4%) cases. ES also established a specific underlying cause for kidney failure for 19 patients who had previously had an unknown etiology. Genetic diagnosis influenced clinical management in 88 recipients (36.1%), facilitated genetic counseling for 18 families (7.4%), and enabled comprehensive assessment of living donor candidates in 35 cases (14.3%). Conclusions: Genetic diagnosis provides critical insights into the pathogenesis of kidney disease, optimizes clinical strategies concerning risk assessment of living donors, and enhances disease surveillance of recipients.