Citations 2
Genetic Testing in the Management of Adult CKD
Chebib, Fouad T. , Wang, Xiangling , Udani, Suneel M. , Westemeyer, Maggie , Clark, Dinah, Zhang, Zhiji, Rasouly, Hila Milo , Kolupaeva, Victoria, Mizani, Mohammad R. , Faravardeh, Arman , Kotte, Sri, Punj, Sumit , Chapman, Steven L. , Schneider, Ronen, Tabriziani, Hossein , Bhorade, Sangeeta , Gharavi, Ali G. , Kolupaeva, Victoria , Bloom, Michelle S , Milo Rasouly, Hila , Mizani, Mohammad R , Dossabhoy, Neville R , Faravardeh, Arman , Demko, Zachary P , Punj, Sumit , Chapman, Steven L , Rabinowitz, Matthew , Tabriziani, Hossein , Bhorade, Sangeeta , Dahl, Neera K , Westemeyer, Maggie , Kolupaeva, Victoria , Chebib, Fouad T , Wang, Xiangling , Udani, Suneel M. , Clark, Dinah, Zhang, Zhiji, Kotte, Sri, Schneider, Ronen, Gharavi, Ali G.
Journal of the American Society of Nephrology | December 3, 2025 | Volume: 37 | Issue: 4 | Pages: 777-789
Key Points Genetic testing in CKD showed diagnostic and clinical utility in the year following reporting of test results. Genetic testing was helpful for or changed management in 86% of patients with a positive finding and 42% with a negative finding. Clinical utility was seen across 12 clinical cohorts, including CKD of unknown etiology and hypertension or diabetes-related nephropathy. Background CKD is a significant public health burden, affecting >800 million people worldwide with significant cost to the health care system. CKD is a disease process with substantial genetic and phenotypic heterogeneity that can obscure a definitive diagnosis, resulting in suboptimal management. Recent guidelines support greater adoption of genetic testing in CKD. We assessed the diagnostic and clinical utility in the year following broad-panel CKD genetic testing. Methods The Renasight Clinical Application, Review, and Evaluation (RenaCARE) study (NCT05846113) was a single-arm, interventional, prospective, multicenter study evaluating the utility of genetic testing with a 385-gene panel on the diagnosis and management of CKD. Clinical history was collected before testing, and nephrologists responded to questionnaires at both 1 month and 1 year after testing. The impact of genetic testing on CKD diagnosis and management were assessed in active study patients at the 1-year time point. Results In a cohort of 1388 CKD patients with 13 pretest clinical categories of CKD, 335 (24%) patients had a positive genetic finding; 1174 had a questionnaire completed at 1 year and were included in the analysis. Genetic testing was reported helpful for clinical management and/or led to a change in management in 86% of patients with a positive test finding and 42% of patients with a negative test finding. In addition, genetic testing resulted in a change in the physician estimation of the 5-year prognosis for 55% of patients with a positive test finding and 18% of those with a negative test finding. Conclusions Supporting the previous results of the RenaCARE study at 1 month, this report demonstrated that genetic testing was helpful in the clinical management and estimated prognosis of patients with CKD. Clinical Trial registry name and registration number: ClinicalTrials.gov, NCT05846113.
Real-world Monitoring of ctDNA Reliably Predicts Cancer Recurrence and Treatment Efficacy in Patients with Resected Stages I-III Colon Cancer
Cohen, Stacey A. , Aushev, Vasily N. , Nagarajan, Arun , Wang, Chongkai , Alyunis, Fadhel, Tejani, Mohamedtaki Abdulaziz, Alqahtani, Ali , Marshall, John C., Chang, Jeremy , Manage, Kevin, George, Giby V., Malhotra, Meenakshi , Chandana, Sreenivasa R , Mehler, Shoshana , Somer, Bradley G. , Babadi, Ellie, Hanna, Diana L. , Chidharla, Anusha , Kasi, Anup , Vosoughi, Elham , Briski, Robert , Azzi, Georges, Katiyar, Vatsala , Sharma, Vivek R. , Shreenivas, Aditya , Fuqua, Jacob , Malla, Midhun , Polite, Blasé N. , Bent, Alisha H., Liu, Minetta C. , Aleshin, Alexey , Cohen, Stacey A , Laliotis, George , Jabbal, Iktej Singh , Fakih, Marwan , Sharif, Saima , Botta, Gregory P. , George, Giby V., Sharma, Shruti , Wu, Christina N. , Dayyani, Farshid , Pedersen, Katrina S. , Chan, Abigail Sy , Chakrabarti, Sakti , Bent, Alisha , Rabinowitz, Matthew , Jurdi, Adham Adel , Kopetz, Scott
Annals of Surgery | August 7, 2025 | Volume: No volume available | Issue: No issue available | Pages: No page available
Objective: In this study, we evaluate the utility of ctDNA analysis in a large cohort of patients for whom ctDNA testing was ordered commercially with real-world application. Summary Background Data: Circulating tumor DNA (ctDNA) has emerged as a prognostic and predictive biomarker for assessing post-surgical molecular residual disease (MRD) and response to treatment. Methods: A real-world data analysis was performed using commercial ctDNA testing (SignateraTM) from patients (N=795, n=5,971 plasma samples) with stage I-III colon cancer treated at multiple US institutions. The association of ctDNA detection within the MRD window, during surveillance, and the impact of ACT was correlated with patient outcomes. Results: ctDNA-positive patients during the MRD window and surveillance showed significantly shorter DFS compared to ctDNA-negative patients (hazard ratio (HR): 9.85, P<0.0001; HR: 26.91, P<0.0001). Multivariate analysis of the MRD window revealed ctDNA-positivity as the most significant factor associated with inferior DFS (adjHR: 7.7, P<0.001). MRD-positive patients who received ACT showed improved DFS compared to patients observed post-surgery (adjHR: 6.1, FDR adj P=0.0007). No ACT benefit was observed in MRD-negative patients (adj HR: 1.20, FDR adj P=0.768). On evaluating ctDNA dynamics from MRD to surveillance, patients who remained ctDNA-positive or converted from negative to positive showed a significantly inferior DFS (HR: 34.40, P<0.0001; HR: 13.65, P<0.0001) compared to persistently ctDNA-negative patients. Conclusions: Postsurgical ctDNA detection is prognostic of relapse and potentially predictive of ACT benefit in patients with resectable colon cancer, which may enable personalized surveillance, intervention, and/or trial options, ultimately improving patient outcomes.