P3.M251: Diagnostic and Clinical Utility of Genetic Testing in Pediatric Nephrology

Background: Approximately 30% of chronic kidney disease in children is inherited. However, the clinical and diagnostic utility of genetic testing in pediatric nephrology is not well described in the literature. Results of this study will shed light on the benefits of testing, to facilitate clinicians determining whether testing is worth the costs, which can exceed $2,000 per test.

Methods: Retrospective chart reviews of 150 patients who underwent Renasight genetic testing at Riley Hospital for Children from 2021-2023 were conducted. Utility of genetic testing was assessed through a variety of parameters, including whether genetic results yielded a diagnosis or informed future care, among others.

Results: Genetic testing yielded a positive result in ~33% of cases, carrier status in ~29% of cases, and VUS only in ~34% of cases. Indications for testing with the highest diagnostic yields included family history of CKD, renal hypoplasia/dysplasia, polyuria, and renal cysts. Significantly, testing in search of genetic causes of isolated hypertension did not yield a diagnosis or change management in any case.
In patients with positive results or conditions with a symptomatic carrier status, genetic testing influenced patient management through medication adjustments, as well as changes in the frequency of labs and provider follow-up. New diagnoses revealed by testing frequently prompted initiation of interdisciplinary care to screen for or manage complications of multisystem pathophysiologies, such as referral for ophthalmologic screening in patients with Alport syndrome. Finally, genetic testing reduced the need for additional diagnostic procedures, including prevention of renal biopsies in 4 patients.
Outside of the treatment course, genetic counseling proved valuable through recommendations such as diet and lifestyle modifications, education regarding reproductive genetic health, and cascade testing of family.

Conclusion: Genetic testing in pediatric nephrology offers a wide scope of clinical and diagnostic utility. Indications for testing that demonstrated the highest diagnostic yields included family history, renal dysplasia/hypoplasia, and renal cysts. In addition to diagnosis, patients benefited from genetic testing through education as well as alterations in treatment course and monitoring.
Based on the results of this study, pursuing testing in search of a genetic cause of isolated hypertension with an unknown etiology should be carefully considered, given the low demonstrated diagnostic yield and potential for large out of pocket costs to patients.