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

Abstract

Background and objectivesActionable 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, & measurementsWe 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.ResultsUsing 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.ConclusionsDeveloping the infrastructure to support return of genetic results in nephrology was resource-intensive, but presented potential opportunities for improving patient care.PodcastThis article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2020_04_16_12481019.mp3

Clinical impact of genomic testing in patients with suspected monogenic kidney disease

“…Many barriers to effective implementation of genomics in nephrology and in other specialties have been described, 36 including physician knowledge gaps surrounding genetics. 37 Knowledge gaps among nephrologists surrounding assessment of patients with GKD, testing processes, patient consent, and counseling were also an important implementation challenge in our study. None of the nephrologists involved in the genetics clinics in this study had formal genetics training, although three had additional research and clinical experience in this area.…”

Clinical Genetic Screening in Adult Patients with Kidney Disease

“…In fact, although historically more clinically apparent in pediatric populations, it is now clear that genetic forms of kidney disease are also highly prevalent in adults, with some studies reporting a Mendelian cause of kidney disease in up to 37% of adult cases (7,8). Establishing a genetic diagnosis has significant implications for nephrology care because it may inform prognosis (9)(10)(11) and selection of therapy (12,13), spare patients from undergoing invasive diagnostic procedures such as a kidney biopsy (14,15), and guide family planning (2).…”

Genomics Integration Into Nephrology Practice

“…A recent Columbia University study described return of clinically actionable results to a nephrology population. However, the testing was completed in a research setting, and ultimately only 62% of individuals could be re-contacted from the original cohort of 108 individuals with medically actionable results (23). In comparison, all individuals in our cohort had return of genetic testing results as part of their routine medical care and were counseled appropriately.…”