A new consensus statement recommended genetic testing for all categories of kidney diseases whenever a genetic cause is suspected and offered guidance on who to test, which tests are the most useful, and how to talk to patients about results.
The statement, published online in the American Journal of Kidney Diseases, is the work of four dozen authors — including patients, nephrologists, experts in clinical and laboratory genetics, kidney pathology, genetic counselling, and ethics. The experts were brought together by the National Kidney Foundation (NKF) with the goal of broadening use and understanding of the tests.
About 10% or more of kidney diseases in adults and 70% of selected chronic kidney diseases (CKDs) in children have genetic causes. But nephrologists have reported a lack of education about genetic testing, and other barriers to wider use, including limited access to testing, cost, insurance coverage, and a small number of genetic counselors who are versed in kidney genetics.
Genetic testing “in the kidney field is a little less developed than in other fields,” said co-lead author Nora Franceschini, MD, MPH, a professor of epidemiology at UNC Gillings School of Global Public Health, Chapel Hill, North Carolina, and a nephrologist who studies the genetic epidemiology of hypertension and kidney and cardiovascular diseases.
There are already many known variants that play a role in various kidney diseases and more are on the horizon, Franceschini told Medscape Medical News. More genetic tests will be available in the near future. “The workforce needs to be prepared,” she said.
The statement is an initial step that gets clinicians thinking about testing in a more systematic way, said Franceschini. “Genetic testing is just another test that physicians can use to complete the story when evaluating patients,” she said. “I think clinicians are ready to implement” testing, said Franceschini. “We just need to have better guidance,” she said.
Who, When, What to Test
The NKF statement is not the first to try to address gaps in use and knowledge. A European Renal Association Working Group published guidelines in 2022.
The NKF Working Group came up with 56 recommendations and separate algorithms to guide testing for adult and pediatric individuals who are considered at-risk (and currently asymptomatic) and for those who already have clinical disease.
Testing can help determine a cause if there’s an atypical clinical presentation, and it can help avoid biopsies, said the group. Tests can also guide choice of therapy.
For at-risk individuals, there are two broad situations in which testing might be considered: In family members of a patient who already has kidney disease and in potential kidney donors. But testing at-risk children younger than 18 years should only be done if there is an intervention available that could prevent, treat, or slow progression of disease, said the authors.
For patients with an established genetic diagnosis, at-risk family members should be tested with the known single-gene variant diagnostic instead of a broad panel, said the group.
Single-gene variant testing is most appropriate in situations when clinical disease is already evident or when there is known genetic disease in the family, according to the NKF panel. A large diagnostic panel that covers the many common genetic causes of kidney disease is recommended for the majority of patients.
The group recommended that apolipoprotein L1 (APOL1) testing should be included in gene panels for CKD, and it should be offered to any patient “with clinical findings suggestive of APOL1-association nephropathy, regardless of race and ethnicity.”
High-risk APOL1 genotypes confer a 5- to 10-fold increased risk for CKD and are found in one out of seven individuals of African ancestry, which means the focus has largely been on testing those with that ancestry.
However, with many unknowns about APOL1, the Working Group did not want to “profile” individuals and suggest that testing should not be based on skin color or race/ethnicity, said Franceschini.
In addition, only about 10% of those with the variant develop disease, so testing is not currently warranted for those who do not already have kidney disease, said the group.
The group also recommended against the use of polygenic risk scores, saying that there are not enough data from diverse populations in genome-wide association studies for kidney disease or on their clinical utility.
More Education Needed; Many Barriers
The authors acknowledged that nephrologists generally receive little education in genetics and lack support for interpreting and discussing results.
“Nephrologists should be provided with training and best practice resources to interpret genetic testing and discuss the results with individuals and their families,” they wrote, adding that there’s a need for Genomic Medicine Boards at academic centers that would be available to help nephrologists interpret results and plot clinical management.
The Working Group did not, however, cite some of the other barriers to adoption of testing, including a limited number of sites offering testing, cost, and lack of insurance coverage for the diagnostics.
Medicare may cover genetic testing for kidney disease when an individual has symptoms and there is an US Food and Drug Administration–approved test. Joseph Vassalotti, MD, chief medical officer for the NKF, said private insurance may cover the testing if the nephrologist deems it medically necessary, but that he usually confirms coverage before initiating testing. The often-used Renasight panel, which tests for 385 genes related to kidney diseases, costs $300-$400 out of pocket, Vassalotti told Medscape Medical News.
In a survey of 149 nephrologists conducted in 2021, both users (46%) and nonusers of the tests (69%) said that high cost was the most significant perceived barrier to implementing widespread testing. A third of users and almost two thirds of nonusers said that poor availability or lack of ease of testing was the second most significant barrier.
Clinics that test for kidney genes “are largely confined to large academic centers and some specialty clinics,” said Dominic Raj, MD, the Bert B. Brooks chair, and Divya Shankaranarayanan, MD, director of the Kidney Precision Medicine Clinic, both at The George Washington University School of Medicine & Health Sciences, Washington, DC, in an email to Medscape Medical News.
Testing is also limited by cultural barriers, lack of genetic literacy, and patients’ concerns that a positive result could lead to a loss of health insurance coverage, said Raj and Shankaranarayanan.
Paper Will Help Expand Use
A lack of consensus has also held back expansion, said the two clinicians. The new statement “may lead to increased and possibly judicious utilization of genetic testing in nephrology practices,” said Raj and Shankaranarayanan. “Most importantly, the panel has given specific guidance as to what type of genetic test platform is likely to yield the best and most cost-effective yield,” they said.
The most effective use is “in monogenic kidney diseases and to a lesser extent in oligogenic kidney disease,” said Raj and Shankaranarayanan, adding that testing is of less-certain utility in polygenic kidney diseases, “where complex genetic and epigenetic factors determine the phenotype.”
Genetic testing might be especially useful “in atypical clinical presentations” and can help clinicians avoid unnecessary expensive and extensive investigations when multiple organ systems are involved, they said.
“Most importantly, [testing] might prevent unnecessary and potentially harmful treatment and enable targeted specific treatment, when available,” said Raj and Shankaranarayanan.
Franceschini and Shankaranarayanan reported no relevant financial relationships. Raj disclosed that he received consulting fees and honoraria from Novo Nordisk and is a national leader for the company’s Zeus trial, studying whether ziltivekimab reduces the risk for cardiovascular events in cardiovascular disease, CKD, and inflammation. He also participated in a study of Natera’s Renasight, a 385-gene panel for kidney disease.
Alicia Ault is a Saint Petersburg, Florida-based freelance journalist whose work has appeared in publications including JAMA and Smithsonian.com. You can find her on X: @aliciaault.
Source link : https://www.medscape.com/viewarticle/new-guidance-genetic-testing-kidney-disease-2024a1000efu?src=rss
Author :
Publish date : 2024-08-06 13:49:48
Copyright for syndicated content belongs to the linked Source.