A nephrologist’s perspective on APOL1-mediated kidney disease

2 min read

The kidneys. These two fist-sized, bean-shaped organs located on either side of the spine are the source of my life’s work. As a nephrologist and the development lead for our genetic kidney disease programs, I may be a bit biased in my passion for the kidneys. But these unsung heroes play a crucial role in filtering blood — removing waste, controlling fluid balance and maintaining electrolyte and blood pressure levels.   

Though we can’t live without them, we don’t necessarily need both to live a healthy life. This may be one of the reasons the kidneys tend to be underrepresented in general and specifically in scientific research. However, when the kidneys don’t work correctly, they can cause different types of kidney diseases that can lead to many health problems and even death. And so, it’s important that we recognize and raise awareness about the importance of these small, but mighty, organs. 


What is APOL1-mediated kidney disease?

APOL1-mediated kidney disease, or AMKD, is a serious genetic kidney disease caused by variants in the APOL1 gene. This gene plays a role in innate immunity and is present in many tissues, including the kidneys. Variants in APOL1 provide protection against certain parasites that cause African sleeping sickness, but they’re also the underlying cause of AMKD.  


I chose to pursue a career in medicine after a discussion with my father, a surgeon, about the intricacies and unknowns of human anatomy and physiology. Prior to joining the world of biotech, I was working as a kidney and pancreas transplant physician at Harvard Medical School.   

Practicing transplant medicine was incredibly fulfilling, but I have also always been curious about how medicines are created. I decided to join the biotech industry to be part of the amazing and leading-edge science that was (and is) happening.   

One thing that informs both my clinical experience and our work at Vertex is the importance of an early and accurate diagnosis. Diagnosis can be difficult because genetic testing is the only way to know if individuals have the APOL1 variants associated with AMKD. The disease can also progress silently, or patients can be misdiagnosed or diagnosed too late, after severe kidney damage or kidney failure has already occurred.
  

An image of a family with the mother smiling at the child who is sitting on his father's shoulders


As a genetic disease, there are also immediate implications for an entire family after diagnosis. Patients can become concerned, even scared, and ask questions like, “Should my family members get tested?” and “What are the chances that my sibling will also get this?” We don’t always have great answers, and until genotyping becomes standard, we have to rely on the highly imperfect proxy of racial phenotypes. We know that people of recent African ancestry in the past 400-600 years (“recent” in scientific terms) can have these risk variants of APOL1. But we also know that not everyone with the risk variants will go on to develop kidney disease. So, there’s still a lot more work to be done to understand this gene and its effects on kidney health. However, in the meantime, we encourage people to have regular checkups with their doctor, talk to their families about whether they have a family history of kidney disease and seek further testing, if needed.   

The firsthand experiences of people living with AMKD — not only their struggles, but also their hopes and dreams for the future — are what I bring with me to my work at Vertex. The potential impact that our program might have on patients, and the fantastic team that’s working toward the goal of delivering a medicine, are what keep us motivated every day.