The kidneys. These two bean-shaped organs located on either side of the spine are the source of my life’s work. Because March is National Kidney Month in the U.S., I wanted to celebrate the occasion and share why it’s important that we recognize and raise awareness about these small, but mighty, organs.
As a nephrologist and clinical development lead for our APOL1-mediated kidney diseases program at Vertex Pharmaceuticals Incorporated, 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 need both of them 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 a myriad of different types of diseases that can lead to many health problems and even death.
What are APOL1-mediated kidney diseases?
APOL1-mediated kidney diseases are genetic forms of various kidney diseases caused by mutations in the APOL1 gene. This gene plays a role in innate immunity and is present in many tissues, including the kidneys. Mutations in APOL1 provide protection against certain parasites that cause African sleeping sickness, but they’re also the underlying cause of some severe kidney diseases.
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.
I decided to join the biotech industry because I’ve always been curious about how medicines are created, and I wanted to be part of this amazing and leading-edge science that was (and is) happening. This role also allows me to pursue my first passion of helping patients and staying connected to the patient community.
People often ask me what having APOL1-mediated focal segmental glomerulosclerosis (FSGS) is like for patients. Focal segmental glomerulosclerosis is a long name, but it perfectly conveys its meaning — “some sections of the kidney filters are scarred”. When a patient comes in, often in the prime of their life, we usually don’t know right away that it’s FSGS.
They may present with swelling in their feet and eyes, fatigue and at times difficulty breathing, but it’s not until a biopsy is performed that evidence of FSGS on the kidneys can be viewed.
What is APOL1-mediated FSGS?
APOL1-mediated FSGS is one type of kidney disease that can be caused by certain variants in the APOL1 gene. It’s a rapidly progressive kidney disorder that results in high levels of protein in the urine, or proteinuria. The disease almost invariably leads to kidney failure, and about half of people living with APOL1-mediated FSGS progress to kidney failure or death within five years.
I recall a patient, a 21-year-old university student, coming in with swelling of her feet and eyes. After a biopsy showed FSGS, we were able to coordinate genotype testing, which confirmed she had the two high-risk variants of APOL1.
The management of APOL1-mediated FSGS is complex. It requires the balancing of reducing proteinuria (protein spilling into the urine), minimizing side effects associated with immunosuppression, and maintaining a patient’s lifestyle. Unfortunately, in this case, the university student had to drop out of school due to treatment side effects, and she recently passed away from a bloodstream infection known as sepsis. As devastating as this outcome is, it’s not uncommon. About 50% of people with APOL1-mediated FSGS progress to kidney failure or death within five years. While dialysis can be a life-saving option for people who progress to end-stage kidney disease, it’s burdensome (three times a week, two to three hours at a time) and also comes with an increased risk of death.
The other thing that’s important to remember is that the genetic nature of APOL1-mediated kidney diseases often generates immediate implications for a family. They 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 high-risk variants of APOL1. But we also know that not everyone with the high-risk variants will go on to develop kidney disease.
The firsthand experiences of people living with APOL1-mediated FSGS — 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 investigational program might have on patients and these small but mighty organs, and the fantastic team that’s working towards delivering a medicine, are what keep us motivated every day.