The Clinical Utility of Genetic Testing in the Diagnosis and Management of Adults with Chronic Kidney Disease

• Published in: Journal of the American Society of Nephrology Vol. 34; no. 12; pp. 2039 - 2050
• Main Authors: Dahl, Neera K, Bloom, Michelle S, Chebib, Fouad T, Clark, Dinah, Westemeyer, Maggie, Jandeska, Sara, Zhang, Zhiji, Milo-Rasouly, Hila, Kolupaeva, Victoria, Marasa, Maddalena, Broumand, Varshasb, Fatica, Richard A, Raj, Dominic S, Demko, Zachary P, Marshall, Kyle, Punj, Sumit, Tabriziani, Hossein, Bhorade, Sangeeta, Gharavi, Ali G
• Format: Journal Article
• Language: English
• Published: United States 01.12.2023
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Genetic Testing; Humans; Middle Aged; Prospective Studies; Renal Insufficiency, Chronic - diagnosis; Renal Insufficiency, Chronic - genetics; Renal Insufficiency, Chronic - therapy; Young Adult
• ISSN: 1046-6673; 1533-3450; 1533-3450
• DOI: 10.1681/ASN.0000000000000249

Accurate diagnosis of a patient's underlying cause of CKD can influence management and ultimately overall health. The single-arm, interventional, prospective Renasight Clinical Application, Review, and Evaluation study assessed the utility of genetic testing with a 385 gene kidney disease panel on the diagnosis and management of 1623 patients with CKD. Among 20.8% of patients who had positive genetic findings, half resulted in a new or reclassified diagnosis. In addition, a change in management because of genetic testing was reported for 90.7% of patients with positive findings, including treatment changes in 32.9%. These findings demonstrate that genetic testing has a significant effect on both CKD diagnosis and management. Genetic testing in CKD has recently been shown to have diagnostic utility with many predicted implications for clinical management, but its effect on management has not been prospectively evaluated. Renasight Clinical Application, Review, and Evaluation RenaCARE (ClinicalTrials.gov NCT05846113 ) is a single-arm, interventional, prospective, multicenter study that evaluated the utility of genetic testing with a broad, 385 gene panel (the Renasight TM test) on the diagnosis and management of adult patients with CKD recruited from 31 US-based community and academic medical centers. Patient medical history and clinical CKD diagnosis were collected at enrollment. Physician responses to questionnaires regarding patient disease categorization and management were collected before genetic testing and 1 month after the return of test results. Changes in CKD diagnosis and management after genetic testing were assessed. Of 1623 patients with CKD in 13 predefined clinical disease categories (ages, 18-96; median, 55 years), 20.8% ( n =338) had positive genetic findings spanning 54 genes. Positive genetic findings provided a new diagnosis or reclassified a prior diagnosis in 48.8% of those patients. Physicians reported that genetic results altered the management of 90.7% of patients with a positive genetic finding, including changes in treatment plan, which were reported in 32.9% of these patients. Genetic testing with a CKD-focused 385 gene panel substantially refined clinical diagnoses and had widespread implications for clinical management, including appropriate treatment strategies. These data support the utility of broader integration of panels of genetic tests into the clinical care paradigm for patients with CKD. ClinicalTrials.gov, NCT05846113 .