Research Awards Recipients

Lay Summary
Nephrotic syndrome is the most common kidney disease among children. Affected children have massive leakage of protein into the urine and, as a consequence, develop body swelling (edema). Most children respond to treatment with steroids, however many of them require repeated courses for frequent relapses of the disease. Long-term use of steroids causes many side effects including obesity, growth retardation, hypertension, cataracts, poor bone health, and cosmetic effects. Minimizing the use of steroids has been identified as the number one priority of the patients and families.
 
A non-steroid drug, rituximab, is now known to be effective in the treatment of nephrotic syndrome, but it is entirely unclear how it works. In this study, we will investigate the mechanisms by which rituximab alleviates the symptoms associated with nephrotic syndrome,

allowing patients to go into remission. Blood collected from affected patients when their disease is active, and after successfully treated with steroid or rituximab, will be analyzed using the state-of-the-art technique called immunophenotyping. One of the investigators in the research team, Dr. Piccirillo, is the leading researcher of this technology in Canada. Moreover, Dr. Takano will use another cutting-edge technology called single cell RNA sequencing, which will tell which genes are active or inactive in individual blood cells from patients. The analyses will allow identification of the blood cells that are active and causing the disease and become inactive after treatment. She will also find out if steroids and rituximab have different effects on blood cells.
 
With this approach, researchers are likely to uncover how this common pediatric disease occurs - it has been a mystery for over five decades. Furthermore, understanding how rituximab works in nephrotic syndrome will enable the identification of patients who are most likely to respond to rituximab thus avoiding steroids. Finally, if the culprit cells are known, new drugs specifically targeting these cells can be developed. The hope is that steroids will not be used at all in the future.