A new study has found that genes cause about 1 in 10 cases of chronic kidney disease in adults, and that identifying the responsible gene has a direct impact on treatment for most of these patients. The study, “Diagnostic Utility of Exome Sequencing for Kidney Disease” co-authored by Dr. Sumit Mohan, associate professor of epidemiology at Columbia Mailman School of Public Health and of Medicine at Columbia University Irving Medical Center, showed 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. The findings are published in the New England Journal of Medicine.
[Photo: Dr. Sumit Mohan]
It is 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 Dr. Ali Gharavi, chief of nephrology at Columbia University Vagelos College of Physicians and Surgeons, and a co-senior author of the study. “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. The study identifies chronic kidney disease as the most common adult disease, outside of cancer, for which genomic testing has been demonstrated as clinically essential, according to the authors.
In the 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 was 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. According to Dr. Gharavi and co-investigators, for several patients, the information received from DNA testing changed the 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.
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.
“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 Dr. Adam Platt, head of Global Genomics Portfolio at AstraZeneca and a co-senior author of the study.
Researchers at Columbia University Irving Medical Center, Columbia Mailman School of Public Health, 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.
See the paper for additional authors and their institutions.
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.