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.
Dr. Jagbir Gill
Expanding Organ Donation in Different Cultural Groups in BC: A Feasibility Study
South Asian (SA) and Chinese Canadians make up nearly 20% of all British Columbians, but account for less than 10% of organ donors. Increasing donation in these communities will increase access to transplantation for all British Columbians.
We are studying ways to improve the process by which South Asian and Chinese families of deceased persons are approached to consent for donation in hospitals. To do this, we will examine all deaths that occur in 5 hospitals in the Lower Mainland of BC over a 1-year period to identify how many South Asian and Chinese Canadians could have been organ donors, how many were asked, and how many consented. This will help us understand if the problem is that we are not asking or that families are not consenting.
We will interview doctors, nurses, and donation specialists to better understand what they see as the barriers to donation in these communities. Additionally, we will interview South Asian and Chinese families that were asked to donate the organs of their deceased loved ones (both when they agreed and didn’t agree to donate) to understand what supported and prevented consent for donation in their cases. Finally, we will ask all of these individuals what they feel could help improve how families are currently asked to donate the organs of their loved ones.
This study will, for the first time, offer solutions from the people directly involved in donation – the medical staff, organ donation specialists, and the families being approached. The results from this study will be used to develop a study in BC hospitals where a culturally tailored intervention will be tested when approaching South Asian and Chinese families for organ donation.
Dr. James Lan
Immunosuppression Reduction and the Risk of De Novo Donor-Specific Antibody Formation After Kidney Transplantation
Kidney transplantation improves the quality of life and longevity of patients with end-stage kidney disease. Despite major improvements in the science of transplantation, a particular form of kidney rejection known as antibody-mediated rejection (AMR) accounts for more than 50% of organ loss. AMR is caused by recipient production of antibodies against unique molecules expressed on the surface of donor cells (donor-specific antibodies, DSA). Under normal circumstances, the recipient does not produce DSA as their immune system is adequately suppressed by the prescribed dosage of anti-rejection medications. However, some patients may experience drug-related side effects such as upset stomach, diarrhea, infection and cancer, which would often trigger a reduction or interruption of certain anti-rejection medications. Although this is routinely practiced in the clinic, it is unknown whether temporary or prolonged reduction of immunosuppression increases the risk of forming DSA, which sets the stage for organ injury and failure down the road.
The goal of this study is to describe the current pattern of prescribed immunosuppression reduction in the clinic and to understand the impact of this practice on DSA development, which portends poor outcomes. This study will help physicians understand the circumstances when it is safe and not safe to reduce immunosuppression. This moves healthcare providers away from the traditional model of “one-size-fits-all”, and allows sophisticated practice guidelines to be implemented at the provincial level to improve patient care.