Enhanced immune monitoring in pediatric kidney transplant recipients
Transplantation is the best and sometimes only treatment for end-stage organ failure. In the last ten years, the lives of more than 20,000 Canadians have been improved, extended, or saved by donated organs. Immunosuppressive drugs make transplantation possible, but they also come with serious side effects such as an increase in infection, cancer and cardiovascular risk. With few new immunosuppressive drugs coming to the market, our goal is to optimize the usage of current therapeutics by individualizing regiments based on better evaluation of patient risk.
The risk of graft rejection is a dynamic process and many factors can influence and activate the immune system. Frequent monitoring of the immune system and its effect on the kidney transplant could help us detect early signs of injury effects. With current monitoring, we can only tell when it is so severe that it has already caused kidney function to deteriorate. Instead, the goal is to adjust immunosuppressant medications before serious damage has occurred.
Up to now, the best test to detect early sign of rejection is a kidney biopsy. However, it’s invasive and not without complication’s risk. In the last decade, our group and others have studied different tests (biomarkers) to assess inflammation and immune activation without the need of a biopsy. We believe that enhanced graft monitoring with a new generation of urine and blood tests would allow a better evaluation of rejection risk. Our goal is to first confirm the feasibility of testing these markers in a clinical setting and to obtain critical information on the real-time utilization of the test parameters needed to design a definitive clinical trial.
Dr. John Boyd & Mark Kearns
Biomarkers of Transplant Viability in Marginal Donor Hearts
The biggest program in heart transplantation is the shortage of donor hearts. This shortage results in the death of significant numbers of patients with end-stage heart failure who would have been eligible to receive a new heart. In order to boost the number of hearts available for transplantation, researchers have been investigating alternative pathways for heart donation. One important alternative is referred to as “donation after circulatory death” or DCD donation. The biggest problem with DCD hearts is that they are injured as a result of the donation process.
If after obtaining DCD hearts, we were able to study their function and degree of injury before placing the heart into a recipient, this would greatly increase the safety of DCD heart transplantation and boost the number of heart transplants performed. Although we have machines that can provide nutrients for the heart and allow us to study it outside a human body, we still can’t precisely identify which hearts would be safe and which would be unsafe for recipients. Addressing this problem would remove a major barrier to the use of DCD hearts for transplantation and reduce the number of people dying unnecessarily on transplant waiting lists.
The main objective of this proposal is to identify candidate genes and proteins that can be used as “biomarkers” (measure indicators) to identify when a DCD heart is too injured for transplantation and therefore unsafe to use for a recipient to a heart with an uncertain outcome.