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Molecular Mechanisms of Childhood Nephrotic Syndrome

Robert Myette
Ottawa Hospital Research Institute
Krescent Post-Doctoral Fellowship
2022 - 2025
$195,000
Kidney Biology

Lay Abstract

Towards a better understanding of kidney disease in children Nephrotic syndrome (NS) is a common cause of protein loss in the urine in children. This leads to swelling, higher risk of kidney damage, infection and early heart disease concerns. Today, the main cause of this disease is unknown. Some children will have a genetic change that they inherit. However, there is a much bigger number of children with NS who did not inherit the disease. These children require many steroid treatments, which we know can impact the growth of children. Steroids can also cause other unpleasant side effects, including weight gain. Therefore, with our project, we are trying to more deeply understand childhood NS. We want to diagnose and treat it better and try to decrease steroid use to avoid these side effects. To do this, we need to understand what happens to a kind of cell in the kidney, called the podocyte cell. Podocyte cells are small. They line the kidney and help to prevent protein loss. They also make urine by filtering our blood. When they are injured and leak protein, they release cell parts that can be collected from the urine and studied. Our lab has found that children with NS have a higher number of these parts in their urine. To study this further, our plan is to use mice and cells to create models of this disease to better understand the reason this happens in children. We are studying a special protein called NOX5 which is responsible for making highly destructive oxygen chemicals which help the body fight infection. When released at the wrong time, these oxygen chemicals can harm the body. In NS, we believe NOX5 is working too hard in the podocyte causing increased oxygen chemicals and injury, which may result in these children having worse kidney disease. This research is very new; however, we expect with this study, and the other studies that come from it, that we will better understand this disease these children face. This is especially important to me as a pediatric nephrologist who cares for these children every day.