The Genetic FSGS Discovery Trailblazing Possible Kidney Disease Treatment

31 million: that is the number of individuals affected by some form of kidney disease in the United States. Although that number is astronomical, the information we know about each individual kidney disease is limited. But roughly 9 years ago, Dr. Martin Pollak, Chief of Nephrology at Beth Israel Deaconess Medical Center, in collaboration with other top researchers and global collaborators, discovered a key piece of information.

Dr. Pollak, his team, and many collaborators, spent years utilizing the latest genetic technology tools to further study, research, and learn about the two common genetic variations in the apolipoprotein L1(APOL1) gene. But what exactly is APOL1?

Every human being inherits two copies of the APOL1 gene, one from mom and one from dad. But this recent research has identified a groundbreaking insight: thosewho inherit two common variations in the APOL1 gene have a ten-fold increased risk for developing kidney diseases like focal segmental glomerulosclerosis (FSGS). These variants are only present in African Americans and others with recent African ancestry.

African Americans are three times more likely to get kidney disease than those of European descent. The APOL1 genotype is common in Africa because it provides protection against parasites, including a disease called African Sleeping Sickness. Transmitted by a fly, this disease is common in eastern Africa and can cause fever, anemia, and even death.

While the gene mutations can be beneficial to some people who still live in Africa, for African Americans it can provide more risk than protection.

“Having these genetic variants doesn’t cause everyone with this genetic profile to develop kidney disease, but it increases their risk by a lot,” Dr. Pollak explained.  “You have to inherit one of these gene variants from both parents, but a lot of times people don’t know the details of their ancestry.  However, many people who have this high-risk APOL1 genotype don’t show any signs or symptoms. It’s possible that many of those with the variation won’t ever develop any form of kidney disease.”

Although Dr. Pollak doesn’t discourage those without signs or symptoms of kidney disease from being genetically tested, he expressed it may not be that helpful in the short-term care of individual patients. While there are currently more potential treatments for FSGS and other glomerular kidney diseases than ever before, none of the drugs are directly linked to assisting with genetic mutations.

“Currently, it’s not clear that knowing the results is going to directly impact the way we take care of people. This could easily change in the future,” Dr. Pollak said.

However, NephCure does encourage those with an increased risk of developing kidney disease to take precautionary measures and make conscious lifestyle decisions to put your kidney health at utmost importance.

Since the breakthrough discovery of APOL1’s relationship to FSGS in 2010, Dr. Pollak and many other investigators have been working on furthering research around this particular gene, in addition to better understanding the specific gene variants. Finding which pathway leads to the main driver of kidney disease is still an open question that many researchers and doctors ponder over.

“There are limitless studies we can do. Right now, we’re focusing on where the damage occurs inside the cells, and we’re trying to understand why some people with variants of the disease get it and some do not,” Dr. Pollak shared.

The APOL1 discovery is a key to unlocking the mystery of kidney disease. Uncovering a connection like this has provided researchers around the world invaluable information to work towards finding potential new treatments targeted at this genetic mutation.

Dr. Pollak is the Chair of NephCure Kidney International’s Scientific Advisory Board. He has served on the Board since 2011. Dr. Pollak is the Chief of Renal Division at Beth Israel Deaconess Medical Center in Boston, MA and a Professor of Medicine at Harvard Medical School.