Astellas/TRFBC Clinical Research GrantFunded Projects

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, this project seeks 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 detect early signs of injury effects. Current monitoring only detects rejection 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. The project team believes that enhanced graft monitoring, with a new generation of urine and blood tests, would allow a better evaluation of rejection risk. The 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.

Primary Investigator: Dr. Tom Blydt-Hansen

Co-investigators: Dr. Caroline Lamarche

Patient Partner: David Boloten and Laura Peeler

For an up-to-date list of publications by Dr. Tom Blydt-Hansen, please see ResearchGate

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. 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 because of the donation process.

Although there are machines that can provide nutrients for the heart and allow it to be studied outside a human body, it is not possible to 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 transplant and therefore unsafe to use for a recipient.

Principal investigator: Dr. John Boyd

Co-investigators: Dr. Mark Kearns

For an up-to-date list of publications by Dr. John Boyd, please see PubMed

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.

This study will look at ways to improve the process by which South Asian and Chinese families of deceased persons are approached to consent for donation in hospitals. The team 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 clarify if the problem is that health professionals are not asking about donation or that families are not consenting.

Doctors, nurses, and donation specialists will be interviewed to better understand what they see as the barriers to donation in these communities. Additionally, 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) will be interviewed to understand what supported and prevented consent for donation in their cases. Finally, the team will ask all 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.

Principal investigator: Dr. Jagbir Gill

Co-investigators: Dr. Marie-Chantel Fortin, Dr. Anita Ho, Dr. David Unger, Dr. George Isac, and Dr. Caren Rose

For an up-to-date list of publications by Dr. Jagbir Gill, please see ResearchGate

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.

Principal investigator: Dr. James Lan

Co-investigators: Dr. Marie-Chantel Fortin, Dr. Anita Ho, Dr. David Unger, Dr. George Isac, and Dr. Caren Rose

For an up-to-date list of publications by Dr. James Lan, please see ResearchGate