Nephrotic syndrome is the most common glomerular kidney disease in children, a condition that damages the kidney filters that clean the blood. The disease primarily affects children aged two to six, causing protein loss in urine and leading to serious complications. Clinicians diagnose nephrotic syndrome based on a combination of symptoms and signs that show that the kidneys are not functioning as they should. Its cause is unknown and there’s no cure. Treatment options are available, but patients’ overall health is greatly impacted due to relapses — recurrences of the syndrome after periods of improvement.
“We want to unlock this mystery,” says Dr. Susan Samuel, a new investigator at BC Children’s Hospital Research Institute (BCCHR) and professor in the Department of Pediatrics at the University of British Columbia. She joined BCCHR in September 2024, after working for more than 15 years as a clinician-scientist at the Alberta Children’s Hospital Research Institute and the University of Calgary. “In my research, I’ve been investigating ways to improve the quality of life of these children, and that includes working towards precision health.”
Dr. Samuel is a pediatric nephrologist who is serving as the director for the Empowering Next-Generation Researchers in Perinatal and Child Health (ENRICH) program, a national network of mentors and learners. We met Dr. Samuel to talk about the importance of research and mentorship.
What motivated you to move to BC?
There are several reasons. BC has a large volume of patients with nephrotic syndrome, so it’s an opportunity to advance research in this area and support more patients. Previously, I had established a good collaboration with Dr. Cherry Mammen, one of the pediatric nephrologists here. Additionally, the Department of Pediatrics, Division of Nephrology, and BCCHR leaders and clinicians were willing to support my research career and the work I want to do here. It’s an honour to work with them. My parents and siblings also live in Vancouver; it is a privilege to live near them, be available to help them, and make new memories together.
How are you planning to advance your research and support children with nephrotic syndrome?
Nephrotic syndrome is thought to be autoimmune — when the body’s immune system mistakenly attacks its own cells. Our group is generating new evidence to prove this. It’s critical to collect blood samples of patients with this condition so we can understand the immune differences between relapse and remission — a period when symptoms are reduced or completely disappear.
I’m facilitating a research program that seeks to uncover the clinical course of pediatric nephrotic syndrome. We completed a national study related to this, and continue to build on our work. Once the child has gone into remission, collecting blood samples before and after treatment will help us understand what is driving the relapse process. With this information, we’d be able to predict which patients will respond to treatment, for example.
There are many children in BC with nephrotic syndrome, so our goal is to develop a translational research hub for children with glomerular kidney disease and a central repository collection of biological samples in Canada.
What’s the current state of your research on nephrotic syndrome?
We’ve been trying to discover which immune signal is involved in the onset of the syndrome and its remission. We need to find out how to turn the disease process off using a targeted drug without causing serious immunosuppressive effects — reduced immune system activity and ability to fight infections and diseases — so we can move towards a precision medicine approach. Recently, research led by my colleagues at the Research Institute of the McGill University Health Centre showed evidence that antibody-secreting cells are activated in relapse states. This activation triggers an autoimmune response that leads to injury to the kidney epithelial cells, which are called podocytes. We published these findings in Nature Communications in 2023.
From the moment a child is diagnosed, what’s the prognosis? How are they impacted?
When a child with nephrotic syndrome comes to a doctor’s office with puffy eyes, they’re often misdiagnosed as having allergies. A urine sample will show if there is protein leak, which is caused by substances in the immune system that destroy the glomerular filtration barrier — a structure in the kidneys that holds back protein in the blood. Protein in the urine is a sign of kidney disease. If a child is suspected to have nephrotic syndrome, the clinician will start treating the patient with an immunosuppressant called prednisone.
For 90 per cent of these children, the syndrome goes into remission, and they will have a good quality of life until there is a relapse. The challenge is prednisone has many side effects in growing children, including skin problems, risk for short stature, and osteoporosis.
You’ve been leading ENRICH, a national training program, for the past six years. Why is it relevant? How does it align with your important work as a researcher?
Athletes find good coaches, train to improve their skills, and are dedicated to their sport. It’s the same with scientists. ENRICH is a community providing mentorship and professional development training to help young professionals become, remain, and succeed as scientists and child health researchers. These types of programs help build a professional identity as a clinician-scientist and remind participants that they’re doing work that makes a difference.
At ENRICH, we have put equity policies in place and created a culture of inclusion where everybody is welcome. Our training program has a dedicated Black and Indigenous scholar pathway. We recognize and value each individual, their perspectives, and their contribution to science.
Everything I do now is only possible because I was a trainee in programs like this one. Medicine advances through people who have ideas that lead to innovation. If we don’t train people to think critically, challenge the status quo, and advance our field, we’ll soon become irrelevant. Individually, we all do our part in leading successful research programs and labs, and training up scholars in graduate programs. However, there is a need to dedicate attention at the national level to train up the next generation of research leaders. I see my role as someone who serves the Canadian child health research community to help build up and equip the next generation of child health research leaders.
