Research Awards Recipients

Lay Abstract

Background: Nephrotic syndrome is the most common kidney disease in children worldwide. Rates of childhood nephrotic syndrome have doubled in the last 10 years in Canada, making it an important public health issue. Nephrotic syndrome is caused by injury to the tiny filters inside the kidney, causing the kidney to leak protein into the urine. This causes a child’s body to swell. If left untreated, children will develop infections, blood clots, and can die. For the last 70 years, children with nephrotic syndrome have been treated with medications commonly referred to as “steroids”, which can stop the kidney from leaking. However, steroids have severe side effects including obesity, diabetes, poor growth, and high blood pressure. In 80% of children, the disease relapses, requiring additional treatment with steroids for each relapse. Relapses lead to frequent clinic visits and hospitalizations, as well as significant missed days from school. This is a big burden for patients, families, and the health care system. Currently, we do not fully understand what causes nephrotic syndrome or why one child will suffer from multiple relapses and another child will not. We are also in need of more targeted less toxic treatments. We also do not understand why children of South Asian and Arab ethnicities are more likely to get nephrotic syndrome than children of European ethnicity.

Purpose: My research will examine patients’ genes to understand more about the disease. Genes provide instructions for making all the proteins in the body. Genes and proteins are some of the most promising new risk factors to identify new drug targets to treat disease. I will study the genetic information from 2000 children with nephrotic syndrome to better understand what causes the disease. This dataset includes genetic information from children of European, South Asian, and Arab ethnicities.

Method: The goals of my research are as follows: 1) I will identify the changes in genes that can predict a child’s specific course of disease (for example, frequent relapses). I will do this by comparing the genetic information from children who have no relapses of disease after receiving “steroids” to children who have multiple relapses of the disease. 2) I will look at the proteins made by a patient’s genes to identify disease-causing proteins as targets for new drugs to treat the disease. I will use the genetic information from children with steroid sensitive nephrotic syndrome to determine the protein levels in their blood. I will then compare these levels to the protein levels of healthy patients. 3) I will identify new changes in genes that increase a child’s risk of developing steroid sensitive nephrotic syndrome to understand why the disease develops in the first place. I will do this by comparing the genetic information from children with steroid sensitive nephrotic syndrome to healthy patients. I will first group the children by ethnicity and study each ethnicity separately. I will then add the results of each group together to capture the full cohort of 2000 children with steroid sensitive nephrotic syndrome.

Anticipated Outcomes: Our work will identify genetic changes that make children at risk for developing nephrotic syndrome and for developing more severe disease. Our work will also help to explain why children of certain ethnicities are at higher risk of disease. By identifying the proteins that cause disease, we will also identify new drug targets to treat the disease.

Patient Engagement: I have involved a lived experience patient and family as well as two nationwide patient councils in my work to explore patient research priorities and to help communicate the findings of my research.

Relevance to Patients/Community: Treatments for childhood nephrotic syndrome have changed very little over the past 70 years. Our work will identify new genes that cause risk for developing nephrotic syndrome and new drug targets to treat the disease. This holds the promise to make the first major advance in the treatment of nephrotic syndrome in decades. Our work will also help us understand why nephrotic syndrome affects children of South Asian and Arab ethnicities more than European children. Ultimately, our work will lead to more accurate diagnosis and safer therapies for children with nephrotic syndrome.

Conclusion: My research program will use genetics and proteomics to help develop more targeted, safer treatments and more individualized care for children with nephrotic syndrome.