For patients with kidney disease, genetic testing may soon be routine

December 26, 2018

NEW YORK, NY (December 26, 2018)--A new study has found that genes cause about 1 in 10 cases of chronic kidney disease in adults, and identifying the responsible gene has a direct impact on treatment for most of these patients.

"Our study shows that genetic testing can be used to personalize the diagnosis and management of kidney disease, and that nephrologists should consider incorporating it into the diagnostic workup for these patients," says Ali Gharavi, MD, chief of nephrology at Columbia University Vagelos College of Physicians and Surgeons, and a co-senior author of the study.

The findings were published on December 26 in the New England Journal of Medicine.

It's estimated that 1 in 10 adults in the United States have chronic kidney disease. Yet, for 15 percent of patients with chronic kidney disease, the underlying cause of kidney failure is unknown.

"There are multiple genetic causes of chronic kidney disease, and treatment can vary depending on the cause," says Gharavi. "But many of the genetic types are rare and can be difficult to detect with traditional diagnostics.

And because kidney disease is often silent in the early stages, some patients aren't diagnosed until their kidneys are close to failing, making it more difficult to find the underlying cause."

DNA sequencing has the potential to pinpoint the genetic culprits, but has not been tested in a wide range of patients with chronic kidney disease.

"Our study identifies chronic kidney disease as the most common adult disease, outside of cancer, for which genomic testing has been demonstrated as clinically essential," says David Goldstein, PhD, director of Columbia University's Institute for Genomic Medicine and a co-senior author of the study.

In this study, researchers used DNA sequencing to look for genetic kidney disorders in 3,315 individuals with various types of chronic or end-stage kidney disease. For 8.5 percent of these individuals, clinicians had not been able to identify the cause of disease.

The researchers found a genetic disorder responsible for about 9 percent of the participants' kidney problems, and DNA testing reclassified the cause of kidney disease in 1 out of 5 individuals with a genetic diagnosis. In addition, DNA testing was able to pinpoint a cause for 17 percent of participants for whom a diagnosis was not possible based on the usual clinical workup.

DNA results had a direct impact on clinical care for about 85 percent of the 168 individuals who received a genetic diagnosis and had medical records available for review. "For several patients, the information we received from DNA testing changed our clinical strategy, as each one of these genetic diagnoses comes with its own set of potential complications that must be carefully considered when selecting treatments," Gharavi says.

About half of the patients were diagnosed with a kidney disorder that also affects other organs and requires care from other specialists. A few (1.5 percent) individuals learned they had medical conditions unrelated to their kidney disease, In all of these cases, the incidental findings had an impact on kidney care. "For example, having a predisposition to cancer would modify the approach to immunosuppression for patients with a kidney transplant," adds Gharavi.

"These results suggest that genomic sequencing can optimize the development of new medicines for kidney disease through the selection of patient subgroups most likely to benefit from new therapies," says Adam Platt, PhD, Head of Global Genomics Portfolio at AstraZeneca and a co-senior author of the study.

While the current study shows the utility of DNA testing in people with kidney disease, another study led by Goldstein and Gharavi found that DNA testing in healthy individuals vastly overestimated the prevalence of kidney disease-associated genetic conditions.

"Altogether, our research suggests that DNA testing may be most useful when balanced with clinical information," says Goldstein.
About the Study

The study, "Diagnostic Utility of Exome Sequencing for Kidney Disease," was published in the New England Journal of Medicine.

Researchers at Columbia University Vagelos College of Physicians and Surgeons, Columbia's Institute of Genomic Medicine, and AstraZeneca's Center for Genomics Research collaborated in the work.

One of the cohorts in this analysis was composed of participants from AstraZeneca's AURORA clinical trial.

Additional authors: Emily Groopman (Columbia), Maddalena Marasa (Columbia), Sophie Cameron-Christie (AstraZeneca Centre for Genomics Research), Slave Petrovski (Columbia and AstraZeneca), Vimla Aggarwal (Columbia), Hila Milo-Rasouly (Columbia), Yifu Li (Columbia), Jun Y. Zhang (Columbia), Jordan Nestor (Columbia), Priya Krithivasan (Columbia), Wan Yee Lam (Columbia), Adele Mitrotti (Columbia), Stacy Piva (Columbia), Byum Hee Kil (Columbia), Debanjana Chatterjee (Columbia), Rachel Reingold (Columbia), Drew Bradbury (Columbia), Michael DiVecchia (Columbia), Holly Snyder (Columbia and University of California at San Francisco), Zueru Mu (Columbia), Karla Mehl (Columbia), Olivia Balderes (Columbia), David A. Fasel (Columbia), Chunhua Weng (Columbia), Jai Radhakrishnan (Columbia), Pietro Canetta (Columbia), Gerald Appel (Columbia), Andrew Bomback (Columbia), Wooin Ahn (Columbia), Natalie Uy (Columbia), Shumyle Alam (Columbia), David J. Cohen (Columbia), Russell Crew (Columbia), Geoffrey Dube (Columbia), Maya Rao (Columbia), Sitharthan Kamalakaran (Columbia), Brett Copeland (Columbia), Zhong Ren (Columbia), Joshua Bridgers (Columbia), Colin Malone (Columbia), Caroline Mebane (Columbia), Neha Dagaonkar (Columbia), Bengt Fellstrom (Uppsala University, Sweden), Carolina Jaefliger (AstraZeneca), Sumit Mohan (Columbia), Simone Sanna-Cherchi (Columbia), Krzysztof Kiryluk (Columbia), Jan Fleckner (AstraZeneca), and Ruth March (AstraZeneca).

The study was supported by grants from the National Institutes of Health (1F30DK116473 and 1T32DK108741-01), the American Society of Nephrology Foundation for Kidney Research, Columbia Institute for Genomic Medicine, and AstraZeneca.

David Goldstein, PhD, received consulting fees from AstraZeneca related to his role as chief advisor for the company's genomic initiative during the conduct of this study. Outside of this work, he is a founder and holds equity in Pairnomix and Praxis Therapeutics, and receives research grants from Janssen, Biogen, and UCB.

Disclosures for the other authors can be found in the paper. Columbia University Irving Medical Center provides international leadership in basic, preclinical, and clinical research; medical and health sciences education; and patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the Vagelos College of Physicians and Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Columbia University Irving Medical Center is home to the largest medical research enterprise in New York City and State and one of the largest faculty medical practices in the Northeast. For more information, visit or

Columbia University Irving Medical Center

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