Gene variants increase the risk of kidney failure

Findings may explain some of the health disparities associated with COVID-19 and could guide efforts to identify individuals at high risk for acute kidney injury and death and develop strategies for personalized therapy, Adriana Hung, MD, MPH, associate professor of medicine in the Reporting Division of Nephrology and Hypertension and lead author of the paper.

“We think it will be very informative to understand whether people have these gene variants that put them at increased risk to make decisions about appropriate therapy,” said Hung.

“We wanted to understand what was behind this increased risk, besides being seriously ill,” she added.

Researchers know that variants in the APOL1 (apolipoprotein L1) gene, found in people of African descent, are associated with chronic kidney disease. More than 1 in 10 individuals of African descent have two variants of APOL1, which appear to have evolved to protect against infection with the parasite that causes African sleeping sickness. APOL1 variants contribute to health disparities in chronic kidney disease among individuals of African ancestry.

Hung and her colleagues wondered whether APOL1 risk variants were associated with AKI in Black patients hospitalized with COVID-19.

They probed this association using data from the Million Veterans Program (MVP), a national program to study how genes, lifestyle, and exposure in the military affect health. and illness. MVP has attracted more than 850,000 diverse veterans over the past 10 years, making it the largest DNA biobank in the world.

The team’s retrospective study included 990 MVP participants of African ancestry who were hospitalized with COVID-19 between March 2020 and January 2021. The researchers used clinical laboratory data to evaluated acute kidney injury in patients, and they adjusted the analysis to account for pre-existing conditions, medications, and other risk factors for AKI.

Of the 990 MVP participants from 63 different hospitals, 12.6% had two variants of APOL1 (high-risk group). Patients in this group were twice as likely to develop severe AKI and die as participants with only one or no APOL1 risk variant. This increased risk persisted even for high-risk patients with normal renal function prior to admission.

Hung said.

Hung noted that drugs that target APOL1 are currently being tested and may provide personalized treatment options for patients with high-risk variants.

“We also wondered if these findings could be extrapolated to individuals with the APOL1 high-risk variant who were critically ill for other reasons,” she said.

Alexander Bick, MD, PhD, assistant professor of Medicine in the Division of Genetic Medicine and co-author of the current report, says using genetic information to inform clinical care is the ultimate goal. goals of VUMC’s precision medicine initiatives.

“Our goal is to put more genetic data into the electronic health record, so that it is readily available at the fingertips of doctors,” says Bick. “This study is another example of how useful genetic information can be; it’s just the beginning of bringing this genetic mutation into a hospital setting,” Bick said.

The study population of 91.4% was male, representing a limitation of the MVP, which is working to increase female participants, Hung said.

Edward Siew, MD, MSCI, associate professor of Medicine in the Department of Nephrology and Hypertension and senior author of the paper, notes that a better understanding of the molecular mechanisms could explain the findings. This and the history for AKI in humans in general are an important future direction.

“There are new biobanking efforts working to obtain tissue and biological samples from patients with AKI, which is an important initial step towards this goal,” Siew said.

Key members of the Vanderbilt research team include Zhihong Yu, PhD, Ran Tao, PhD, Hua-Chang Chen, PhD, Otis Wilson, Robert Greevy, PhD, Cecilia Chung, MD, MPH, Elvis Akwo, MD, PhD, Michael Matheny, MD, MS, MPH, and Cassianne Robinson-Cohen, PhD.

This study was supported by the Veterans Health Administration’s COVID-19 MVP Science Program and a VA Clinical Science Research and Development investigator granting Hung to study the Genetics of Kidney disease and Hypertension. Siew and Matheny are supported by a VA Health Services Research and Development grant.

Source: Eurekalert

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