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

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.

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.

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.

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.