Implementation and Feasibility of Clinical Genome Sequencing Embedded Into the Outpatient Nephrology Care for Patients With Proteinuric Kidney Disease

Maddalena Marasa; Dina F Ahram; Atteeq U Rehman; Adele Mitrotti; Avinash Abhyankar; Namrata G Jain; Patricia L Weng; Stacy E Piva; Hilda E Fernandez; Natalie S Uy; Debanjana Chatterjee; Byum H Kil; Jordan G Nestor; Vanessa Felice; Dino Robinson; Dilys Whyte; Ali G Gharavi; Gerald B Appel; Jai Radhakrishnan; Dominick Santoriello; Andrew Bomback; Fangming Lin; Vivette D D'Agati; Vaidehi Jobanputra; Simone Sanna-Cherchi

doi:10.1016/j.ekir.2023.05.021

Implementation and Feasibility of Clinical Genome Sequencing Embedded Into the Outpatient Nephrology Care for Patients With Proteinuric Kidney Disease

Kidney Int Rep. 2023 May 26;8(8):1638-1647. doi: 10.1016/j.ekir.2023.05.021. eCollection 2023 Aug.

Authors

Maddalena Marasa¹, Dina F Ahram¹, Atteeq U Rehman², Adele Mitrotti¹, Avinash Abhyankar², Namrata G Jain³, Patricia L Weng⁴, Stacy E Piva¹, Hilda E Fernandez¹, Natalie S Uy³, Debanjana Chatterjee¹, Byum H Kil¹, Jordan G Nestor¹, Vanessa Felice², Dino Robinson², Dilys Whyte⁵, Ali G Gharavi¹, Gerald B Appel¹, Jai Radhakrishnan¹, Dominick Santoriello⁶, Andrew Bomback¹, Fangming Lin³, Vivette D D'Agati⁶, Vaidehi Jobanputra^{2

7}, Simone Sanna-Cherchi¹

Affiliations

¹ Division of Nephrology, Department of Medicine, Columbia University, New York, USA.
² The New York Genome Center, New York, USA.
³ Division of Pediatric Nephrology, Department of Pediatrics, Columbia University, New York, USA.
⁴ Division of Pediatric Nephrology, Department of Pediatrics, UCLA Medical Center and UCLA Medical Center-Santa Monica, Los Angeles, California, USA.
⁵ Pediatric Specialty Center of Good Samaritan Hospital Medical Center, Babylon, New York, USA.
⁶ Department of Pathology and Cell Biology, Renal Pathology Division, Columbia University Medical Center, New York, USA.
⁷ Department of Pathology and Cell Biology, Columbia University, New York, USA.

Abstract

Introduction: The diagnosis and management of proteinuric kidney diseases such as focal segmental glomerulosclerosis (FSGS) are challenging. Genetics holds the promise to improve clinical decision making for these diseases; however, it is often performed too late to enable timely clinical action and it is not implemented within routine outpatient nephrology visits.

Methods: We sought to test the implementation and feasibility of clinical rapid genome sequencing (GS) in guiding decision making in patients with proteinuric kidney disease in real-time and embedded in the outpatient nephrology setting.

Results: We enrolled 10 children or young adults with biopsy-proven FSGS (9 cases) or minimal change disease (1 case). The mean age at enrollment was 16.2 years (range 2-30). The workflow did not require referral to external genetics clinics but was conducted entirely during the nephrology standard-of-care appointments. The total turn-around-time from enrollment to return-of-results and clinical decision averaged 21.8 days (12.4 for GS), which is well within a time frame that allows clinically relevant treatment decisions. A monogenic or APOL1-related form of kidney disease was diagnosed in 5 of 10 patients. The genetic findings resulted in a rectified diagnosis in 6 patients. Both positive and negative GS findings determined a change in pharmacological treatment. In 3 patients, the results were instrumental for transplant evaluation, donor selection, and the immunosuppressive treatment. All patients and families received genetic counseling.

Conclusion: Clinical GS is feasible and can be implemented in real-time in the outpatient care to help guiding clinical management. Additional studies are needed to confirm the cost-effectiveness and broader utility of clinical GS across the phenotypic and demographic spectrum of kidney diseases.

Keywords: feasibility; focal segmental glomerulosclerosis; genetic diagnosis; genome sequencing; implementation; proteinuria.

Grants and funding

KL2 TR001874/TR/NCATS NIH HHS/United States