Gene variants increase the risk of kidney failure in COVID-19 patients

Having two gene variants that are known to be more common in people with African ancestry, and that are also known to predispose people to kidney disease, doubles the risk of severe kidney injury and death in people with COVID-19.

Researchers from the Vanderbilt University Medical Centre, Nashville, Tennessee looked at the impact of two variants – known as G1 and G2, and found in the gene encoding apolipoprotein L1 (APOL1) – on veterans hospitalised with COVID-19. They found that having both of the risk variants put individuals at approximately twice the risk of severe acute kidney injury or death, compared to those who had only one variant or neither of the variants. People with these variants were at risk even if they had normal kidney function before infection with SARS-CoV-2, the virus that causes COVID-19.

'We think it will be very informative to understand if people have these gene variants that put them at increased risk to make decisions about tailoring therapy for them,' said Dr Adriana Hung, the lead author of the study. The study was undertaken as part of the Million Veteran Program, which aims to find how genes and lifestyle can affect disease in people in the military.

A previous study published in the Clinical Journal of the American Society of Nephrology had shown that developing acute kidney injury with COVID-19 was more likely in patients who were black and male, as well as in those who had obesity, type II diabetes and high blood pressure. The new study looked at a much larger group of patients, and considered their genomic data.

However, due to the population that the study programme drew upon, more than 90 percent of the patients were male. This may limit the applicability of these findings to women.

The study used data from 990 veterans of African ancestry who were hospitalised with COVID-19 between March 2020 and January 2021. Half of those participants who had two risk alleles developed acute kidney injury, and one in five died.

G1 and G2 are believed to have been selected in certain West African populations, because having at least one of the variants protects against infection from the parasite that causes African sleeping sickness. However, care should be taken not to generalise the findings of this study to any specific group, as only 13 percent of black Americans have variants that put them at risk. Furthermore, the frequency of G1 and G2 varies greatly, even among West African populations.

Coauthor Dr Alexander Bick, commented that this study is part of efforts to develop precision medicine, saying: 'Our goal is to bring more genetic data into the electronic health record, so that it's available at clinicians' fingertips. This study is another example of how genetic information is going to be useful; it's just the beginning for bringing this gene mutation into the hospital setting.'