Grant: Operating Grant

Kidney transplantation is a life-saving treatment for children with end-stage kidney failure. A major threat to success is rejection, where the body's immune system attacks and destroys the transplanted kidney. If rejection isn't treated early, it results in permanent injury that can lead to loss of the transplant and a return to dialysis. Currently, tests that monitor kidney function will miss early or mild rejection. Instead, we screen with repeated kidney biopsies, which are risky and unpleasant. This research program will use proven techniques to identify signs of kidney injury and rejection in the urine of children who have had a kidney transplant. It will focus on the first year after transplant, since this is the highest risk for rejection. We will look for metabolites and chemokines that we have tested before to identify when injury or rejection is present. Metabolites are small molecules produced by our cells as part of their function or as waste products. Chemokines are a different type of molecule that is produced by our immune system to signal inflammation. We already know some of the changes that occur with rejection. We now plan to validate that the same changes are present in other Canadian children with kidney transplants. We will ask children with a new kidney transplant and their families to participate in this study. They will provide a urine sample for analysis whenever they have a kidney biopsy and also at regular intervals after transplant. We will verify the metabolite and chemokine levels that are linked to rejection, and could predict rejection in other children. Once it has been refined, we will determine whether it improves outcome by using it as a test for real-time monitoring and limit our use of regular kidney biopsies. We hope to demonstrate that this will improve the accuracy to detect rejection early, reduce the number of biopsies and improve the health and long-term kidney function of children with a transplant.