Rapid Genome and Exome Sequencing as a First-Line Diagnostic Tool for Hospitalized Pediatric Kidney Disease Patients.

BACKGROUND: Previous efforts have demonstrated the utility of exome sequencing approaches in improving diagnosis and management of kidney diseases with underlying genetic etiologies. Rapid clinical genome sequencing is increasingly used as a first line clinical diagnostic modality in the inpatient setting, yet its utility for individuals with kidney disease has not been examined. METHODS: We conducted a retrospective analysis of pediatric inpatients with structural kidney abnormalities, pathological microscopic kidney abnormalities, and/or laboratory evidence of kidney disease who underwent rapid clinical genome or exome sequencing while hospitalized at a single tertiary pediatric center over a 42-month period. Diagnostic yield and the impact of genetic diagnoses on inpatient clinical management were assessed. RESULTS: We identified 77 pediatric patients who met the study criteria, ranging in age from 1 day to 17 years at time of testing. Genetic variants considered explanatory or likely explanatory of the patient's phenotype were identified in 47% (36/77) of cases. Results spanned monogenic disorders caused by single nucleotide variants to multi-gene disorders ranging from large deletions or duplications, with explanatory findings across three defined categories (macroscopic, microscopic, and other). Among individuals given a genetic diagnosis, 92% (33/36) had results that were clinically actionable beyond disease-specific guidance, resulting in modifications to clinical management including targeted laboratory evaluations, imaging studies, subspecialty referrals, and initiation of gene-targeted therapies. CONCLUSIONS: Rapid exome or genome sequencing for pediatric inpatients with kidney disease yielded a diagnosis in 47% of cases, with high rates of actional clinical impact during the initial hospital admission.