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. 2020 May 7;15(5):651-664.
doi: 10.2215/CJN.12481019. Epub 2020 Apr 16.

Pilot Study of Return of Genetic Results to Patients in Adult Nephrology

Jordan G Nestor  1 , Maddalena Marasa  1 , Hila Milo-Rasouly  1 , Emily E Groopman  1 , S Ali Husain  1 , Sumit Mohan  1   2 , Hilda Fernandez  1 , Vimla S Aggarwal  3 , Dina F Ahram  1 , Natalie Vena  1   4 , Kelsie Bogyo  1   3 , Andrew S Bomback  1 , Jai Radhakrishnan  1 , Gerald B Appel  1 , Wooin Ahn  1 , David J Cohen  1 , Pietro A Canetta  1 , Geoffrey K Dube  1 , Maya K Rao  1 , Heather K Morris  1 , Russell J Crew  1 , Simone Sanna-Cherchi  1 , Krzysztof Kiryluk  1 , Ali G Gharavi  1   4
Affiliations

Pilot Study of Return of Genetic Results to Patients in Adult Nephrology

Jordan G Nestor et al. Clin J Am Soc Nephrol. .

Abstract

Background and objectives: Actionable genetic findings have implications for care of patients with kidney disease, and genetic testing is an emerging tool in nephrology practice. However, there are scarce data regarding best practices for return of results and clinical application of actionable genetic findings for kidney patients.

Design, setting, participants, & measurements: We developed a return of results workflow in collaborations with clinicians for the retrospective recontact of adult nephrology patients who had been recruited into a biobank research study for exome sequencing and were identified to have medically actionable genetic findings.

Results: Using this workflow, we attempted to recontact a diverse pilot cohort of 104 nephrology research participants with actionable genetic findings, encompassing 34 different monogenic etiologies of nephropathy and five single-gene disorders recommended by the American College of Medical Genetics and Genomics for return as medically actionable secondary findings. We successfully recontacted 64 (62%) participants and returned results to 41 (39%) individuals. In each case, the genetic diagnosis had meaningful implications for the patients' nephrology care. Through implementation efforts and qualitative interviews with providers, we identified over 20 key challenges associated with returning results to study participants, and found that physician knowledge gaps in genomics was a recurrent theme. We iteratively addressed these challenges to yield an optimized workflow, which included standardized consultation notes with tailored management recommendations, monthly educational conferences on core topics in genomics, and a curated list of expert clinicians for patients requiring extranephrologic referrals.

Conclusions: Developing the infrastructure to support return of genetic results in nephrology was resource-intensive, but presented potential opportunities for improving patient care.

Podcast: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2020_04_16_12481019.mp3.

Keywords: adult; biological specimen banks; chronic kidney disease; cohort studies; exome; familial nephropathy; genetic renal disease; genetic testing; genomics; human genetics; humans; kidney diseases; medical genetics; nephrology; patient care; pilot projects; referral and consultation; retrospective studies; whole exome sequencing; workflow.

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Figures

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Graphical abstract
Figure 1.
Figure 1.
Developing a standardized workflow for return of medically actionable genetic findings to nephrology research participants. Optimization of a workflow for return of results in nephrology: the workflow was iteratively developed on the basis of feasibility and challenges encountered with return of results, alongside provider feedback. The strategies implemented to address various challenges faced with return of results informed the final optimized workflow, which included five key steps: (1) genetic sequence analysis; (2) notifying the referring nephrologist; (3) participant recontact; (4) return of clinically confirmed results with post-test counseling; and (5) clinical application of findings.
Figure 2.
Figure 2.
Results of piloting return of results workflow among genetic study research participants. The return of results study flow: we identified 213 study participants with medically relevant findings. Of these participants, 113 were adults who opted for return of actionable findings as part of their informed consent and were eligible for thorough review of their electronic health record, an additional nine participants were excluded as they had attained a genetic diagnosis via clinical genetic testing outside of this workflow. The remaining 104 participants were all included in the pilot cohort. Of these 104 participants, seven individuals (7%) were dual enrolled in the eMERGE Network’s phase 3 study and consented for clinical-grade sequencing on the eMERGE-seq platform. In total, we successfully recontacted 64 of the 104 (62%) participants, including all seven individuals crossenrolled in the eMERGE study. Among the 48 individuals who consented for clinical-grade sequencing (including the seven participants enrolled in eMERGE), 41 had their results returned by our nephrogenetics team. In one case, the research-level findings were not confirmed due to a technical limitation of the confirmatory test modality used (detailed in Section S2 of the Supplemental Material).
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