Uncovering the genes behind kidney disease

New research offers a 'key roadmap' for understanding the mechanisms of chronic kidney disease.

Dave Yasvinski 3 minute read August 17, 2021
genes kidney disease

Researchers are calling the genetic study a milestone for understanding chronic kidney disease. Getty

A new study has just unlocked the genetic underpinnings of chronic kidney disease, identifying 182 genes likely responsible for kidney function and opening the door to new therapies to help the roughly four million Canadians currently living with the disease.

The research, published in the journal Nature Genetics, also uncovered the main cell types that play a role in kidney disease and found 88 genes related to hypertension. “This is a key roadmap for understanding the mechanisms of chronic kidney disease,” said Katalin Susztak, principal investigator of the study and a professor in the division of Renal-Electrolyte and Hypertension at the University of Pennsylvania. “Fortunately, some of the genes we’ve identified for kidney disease can be targeted with existing drugs.”

Approximately one in 10 Canadians have been diagnosed with kidney disease, according to the Kidney Foundation, with more than 50,000 currently undergoing treatment for kidney failure. In 2018, the disease was the 10th leading cause of death in the country. Dialysis, the primary treatment for kidney failure, costs the Canadian health care system $100,000 per year, per patient, pushing the economic toll of chronic kidney disease into the neighbourhood of $40-billion annually.

While diabetes and high blood pressure are both known to have a hand in the development of chronic kidney disease, genetic factors have gained attention as a key contributor lately. In an attempt to crack the code hidden within the genetic variations associated with the disease, researchers looked to genome-wide association studies (GWAS) for clues. These genetic studies, which include the DNA variations of hundreds of thousands of people, helped narrow the search to 300 or so regions of the human genome linked to the disease but had, so far, been unable to pinpoint the specific genes, cell types and mechanisms at play.

“The existing maps have indicated regions in the genome for kidney disease heritability — like an initial treasure map — but, until now, we did not know where the treasure chest was located or how it looked,” Susztak said. “Our goal was to find the exact location of the treasure and to open up the box to see what was inside.”

One of the biggest challenges the team faced in using this initial map to locate specific genes was the fact that most of the genetic variations that cause kidney disease also alter how these genes are regulated. To account for this, researchers collected and manually dissected 659 human kidney samples and analyzed the expression of each gene and its genetic variation. This allowed them to use a newly created single cell sequencing method to identify the gene expression and regulation data for each type of human kidney cell. With this information, they were able to zero in on the specific cell types that are altered by genetic variants.

Using this process, researchers were able to pinpoint nearly 200 genes related to kidney function and 100 tied to hypertension. It also helped them better understand exactly how some drugs used to treat kidney cancer actually work by allowing them to see which genes they act upon. With an accurate roadmap of the disease now in place, other innovative treatments may soon follow. “We have used these drugs for several decades, but now we know why they work so effectively,” Susztak said.

“This study represents a very important milestone for the nephrology field and the millions of patients currently affected by chronic kidney disease.”

Dave Yasvinski is a writer with Healthing.ca

For more information on kidney disease, support or to connect with other patients, visit Kidney Foundation.

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