• David Hartell

Announcing the results of the 2018 CDTRP Research Innovation Grant Competition - 18 new projects add


The Canadian Donation and Transplantation Research Program (CDTRP), in partnership with Astellas Canada, the Alberta Transplant Innovation Fund, the University Health Network in Toronto, the Kidney Foundation of Canada, Cystic Fibrosis Canada, the Transplant Research Foundation of British Columbia, Big Gifts for Little Lives, and the University of Montréal are pleased to share the results of the 2018 CDTRP Research Innovations Grant Competition. We received 48 applications to this competition and are excited about integrating the following 18 new funded studies into the research Theme structure of the CDTRP (full lay abstracts listed at the end).

"The CDTRP received a record number of applications to this year’s Innovation Grant competition and we have welcomed new and exciting national and regional partners”, says Dr. Lori West, Director of the CDTRP. “This competition is clearly an important resource to the community and we are committed to supporting and integrating these exciting new projects.

"We know research will be what transforms transplant into a cure so that kids like Addison can live long and healthy lives”, says Elaine Yong, founder of the Addison Fund and mother of a pediatric heart transplant recipient. “We are proud and excited to support two innovative research projects specifically focused on the needs of pediatric transplant patients.

"The Kidney Foundation of Canada is a proud partner of the CDTRP Innovation Grant. We congratulate Drs Foster, Fortin and Janaudis-Ferreira on their innovative and successful applications," said Elizabeth Myles, National Executive Director. "Pilot projects like these generate new knowledge that will help to improve the health of kidney transplant donors and recipients."

Together, our partners invested $540,000 in new peer reviewed grant funding that will increase access to donation and improve outcomes for transplant recipients. This collective effort and success would not be possible without the dedication and commitment of our partners across Canada. We would also like to thank and acknowledge the hard work of the CDTRP New Initiatives Committee and all our volunteer Peer Reviewers for participating in the CDTRP review process and for upholding an excellent level of professionalism and quality.

The CDTRP, along with our partners, will launch a new grant competition in the fall of 2019. Please visit www.cdtrp.ca often for new information on upcoming grant competitions.

The recipients of the 2018 CDTRP Astellas Research Innovation Grants are:

Dr Markus Selzner

University of Toronto, University Health Network, Toronto, ON

Study Title: Indocyanine Green (ICG) Fluorescence imaging during Normothermic Ex Vivo Liver Perfusion (NEVLP) in swine model of Donation after Cardio-circulatory Death (DCD)

New CDTRP study within Theme 3

Dr Deepali Kumar

University of Toronto, University Health Network, Toronto, ON

Study Title: Ex-vivo Delivery of Rituximab to Prevent PTLD in EBV mismatch Lung Transplant Recipients: A Pilot Trial.

New CDTRP study within Theme 3 and 4

Dr Maureen Meade

McMaster University, Hamilton, ON

Study Title: Research Consent in Donation Trials: A Grounded Theory Pilot Study

New CDTRP study within Theme 2

​​

Dr Shaifali Sandal

McGill University, Montréal, QC

Study Title: Health delivery systems, Health professionals and barriers to living donor kidney transplantation across Canada: a comparative and mixed methods study

New CDTRP study within Theme 1 and 2

​​

Dr Jason Shahin

McGill University, Montréal, QC

Study Title: Is the process of end of life care different for DCD donors vs. non-donors? An exploration of observational data on the process of withdrawal of life sustaining therapies in the intensive care unit.

New CDTRP study within Theme 2

​​

Dr Samantha Anthony

University of Toronto, SickKids, Toronto, ON

Study Title: inSight: Creation of an Electronic Patient-Reported Outcome Measure Platform in Pediatric Transplantation

New CDTRP study within Theme 5

The recipients of the 2018 CDTRP Alberta Transplant Innovation Fund Research Innovation Grant are:

Dr Allan Murray

University of Alberta, Edmonton, AB

Study Title: Apelin receptor signaling and lymphocyte function in allograft rejection

New CDTRP study within Theme 3 and 4

Anne Halpin

University of Alberta, Edmonton, AB

Study Title: Knowing the unknown: adding an HLA-specific memory B cell assay to the toolbox

New CDTRP study within Theme 3 and 4

Dr James Shapiro

University of Alberta, Edmonton, AB

Study Title: Gene correction in human induced pluripotent stem cells from type-1 diabetic patients by CRISPR/Cas9 genome editing.

New CDTRP study within Theme 4

Dr Diana Mager

University of Alberta, Edmonton, AB

Study Title: Biology of skeletal muscle and sarcopenia in children with ESLD awaiting LTx

New CDTRP study within Theme 5

The recipients of the 2018 CDTRP Kidney Foundation of Canada Research Innovation Grant are:

Dr Bethany Foster

McGill University, Montréal, QC

Study Title: Associations between Sex Hormone Levels and Immune Profiles among Kidney Transplant Recipients

New CDTRP study within Theme 4

Drs Tania Jaudis-Ferreira and Marie-Chantal Fortin

McGill University and Université de Montréal, Montréal, QC

Study Title: Acceptability and feasibility of the Kidney Transplant Physical Activity and Social Club (KEeP ACTIVe Club)

New CDTRP study within Theme 5

The recipients of the 2018 CDTRP Addison Fund - TRFBC Research Innovation Grant competition and the CDTRP Big Gifts for Little Lives Research Innovation Grant competition are:

Dr Karina Top

Dalhousie University, Halifax, NS

Study Title: Optimizing varicella immunization in children and youth with solid organ transplants to prevent disease and improve long-term health

New CDTRP study within Theme 5 and 4

Dr. Tom Blydt-Hansen

University of British Columbia, Vancouver, BC

Study Title: Investigating serum immunometabolomic profiles associated with pediatric kidney and heart transplant alloimmune outcomes

New CDTRP study within Theme 5 and 4

The recipient of the 2018 CDTRP Cystic Fibrosis Canada Research Innovation Grants is:

Dr Emmanuelle Brochiero

Université de Montréal

Study Title: From the donor to the recipient: Identification of novel biomarkers and therapeutic targets associated with primary graft dysfunction after lung transplantation

New CDTRP study within Theme 2 and 3

The recipients of the 2018 CDTRP UHN Multi-Organ Transplant Program Research Innovation Grant are:

Dr Mamatha Bhat

University of Toronto, University Health Network, Toronto, ON

Study Title: Development and Validation of a Practical Web-based Risk Calculator for Post-Transplant Diabetes using Machine learning

New CDTRP study within Theme 5

​​

Dr Mingyao Liu

University of Toronto, University Health Network, Toronto, ON

Study Title: Cystic fibrosis and donor specific injuries in human lung transplants: a comprehensive bioinformatics and systems biology approach

New CDTRP study within Theme 3

The recipient of the 2018 CDTRP Université de Montréal Research Innovation Grants is:

Dr Michaël Chassé

Université de Montréal

Study Title: Early detection of potential organ donors using machine learning algorithms compared to traditional epidemiological approaches: Phase 1 of the COMPASS Network

New CDTRP study within Theme 1 and 2

LAY ABSTRACTS

Dr Markus Selzner

University of Toronto, University Health Network, Toronto, ON

Study Title: Indocyanine Green (ICG) Fluorescence imaging during Normothermic Ex Vivo Liver Perfusion (NEVLP) in swine model of Donation after Cardio-circulatory Death (DCD)

New CDTRP study within Theme 3

Abstract :

For end-stage liver disease patients, liver transplantation is an established curative treatment. Donation

after Cardio-circulatory Death (DCD) is a strategy to overcome the shortage of grafts, but we are currently

unable to predict the extend of ischemic injury on DCD grafts. Normothermic Ex Vivo Liver Perfusion

(NEVLP) is novel technique to preserve and assess these grafts and has possibility for reconditioning. We

established the porcine model of NEVLP prior to liver transplantation and a clinical trial of NEVLP with

marginal graft is now ongoing in Toronto General Hospital. However, no parameters are currently

available to assess whole liver function, determine arterial flow, and evaluate biliary ischemia.

Indocyanine Green (ICG) is a substance that is exclusively cleared by hepatocytes and excreted into the

bile in an ATP dependent mechanism. In addition, ICG emits fluorescence when excited by near-infrared

light, which can be quantified in real-time by image analysis.

Our hypothesis is that by ICG injection into the arterial side of the perfusion circuit we can quantify

arterial liver perfusion and determine biliary epithelial cell function. Better assessment of arterial liver

flow and bile duct injury will allow us to use more extreme marginal grafts and extend the donor pool.

Dr Deepali Kumar

University of Toronto, University Health Network, Toronto, ON

Study Title: Ex-vivo Delivery of Rituximab to Prevent PTLD in EBV mismatch Lung Transplant Recipients: A Pilot Trial.

New CDTRP study within Theme 3 and 4

Abstract :

Post-transplant lymphoproliferative disorders (PTLD) can present as a type of malignancy that limits patient and graft survival after solid organ transplantation. Many early PTLDs are driven by the Epstein-Barr Virus (EBV). Once acquired, EBV virus establishes latency in B-cells and can reactivate under immunosuppression. The highest risk transplant type to develop PTLD are lung transplants who have newly acquired EBV from their donors (D+/R-). There are no good modalities to prevent PTLD from developing after transplant. Rituximab is a monoclonal antibody that depletes B-cells thereby also reducing the burden of EBV. However, rituximab can have toxicities when given intravenously including infusion reactions and increased risk of reactions. Furthermore, more than one dose is usually required. The Toronto Transplant program has developed a technology called ex vivo lung perfusion that repairs lungs outside of the body.

Preliminary work has shown that rituximab given through the EVLP circuit can coat B-cells. We have also shown that there is no toxicity to the lung by giving rituximab. The current highly novel study proposes to treat donor lungs ex-vivo with rituximab in order to decrease the amount of B-cells and EBV in the graft. These lungs will then be transplanted into EBV negative patients with the hope that transmission of EBV would be reduced or prevented. Ten patients will be included in the current trial. Outcomes include safety, EBV viral load, and B-cell measurements in biopsies. We hope to use this pilot trial to generate data to perform a larger multicenter randomized study through the CDTRP.

Dr Maureen Meade

McMaster University, Hamilton, ON

Study Title: Research Consent in Donation Trials: A Grounded Theory Pilot Study

New CDTRP study within Theme 2

Abstract :

The need for donated organs vastly outweighs those that are available for transplant. One way to bridge this gap is to investigate optimal medical care for deceased organ donors in the intensive care unit. This has the potential to increase both the number of organs available and the quality of those that are ultimately transplanted. There are issues however, around understanding how stakeholders such as transplant recipients feel about this research, and the best way from their perspectives to obtain their consent for this research. This study seeks to assess the feasibility of a larger qualitative study that will explore these issues through one-on-one interviews with kidney, liver, and lung transplant recipients. We are looking to see if we can recruit individuals in a single centre from three different organ transplant types and find out how transplant recipients feel about organ donor research. This study is important because it will provide important foundational information about issues that have, so far, limited the ability to conduct ethical research with organ donors.

Dr Shaifali Sandal

McGill University, Montréal, QC

Study Title: Health delivery systems, Health professionals and barriers to living donor kidney transplantation across Canada: a comparative and mixed methods study

New CDTRP study within Theme 1 and 2

Abstract :

Patients who have end-stage renal disease need dialysis or a kidney transplant to survive. Kidney transplantation from a living donor is considered to be the best treatment option as it is associated with better longevity for the patient and lower costs to the health care system. Yet, the rates of living donation at several centers in Canada are low and are decreasing despite new initiatives. In addition, there are significant interprovincial variations. In the provinces of Quebec, Ontario, and British Columbia, <15%, 30-40% and 50-60% of the kidney transplants done annually are from living donors, respectively.Currently, efforts to increase living donation tend to focus on the patient, on teaching and training them how to seek donors. This has not been shown to be effective for all patients and is thought to have created an unfair system favoring those with the means to find living donors. However, health professional barriers to discussing living donation with their patients have not been well studied. In addition, whether they vary by the rate of living donation is not known. Lastly, what elements of a health delivery system contribute to high rates is not recognized. Our study aims to quantify and compare barriers to living donor kidney transplantation discussions as identified by the health professionals. Also, we want to conduct a case study of BC transplant, the province with the best performance in living donor kidney transplantation. We want to identify strategies, programs, mandates and operating structure that might be contributing to British Columbia being a leader in living donor kidney transplantation.

Dr Jason Shahin

McGill University, Montréal, QC

Study Title: Is the process of end of life care different for DCD donors vs. non-donors? An exploration of observational data on the process of withdrawal of life sustaining therapies in the intensive care unit.

New CDTRP study within Theme 2

Abstract :

Severely injured and seriously ill people who are eligible for donating organs after a declaration

of death using circulatory criteria (e.g. the stopping of the heart and loss of blood pressure) must

first go through the process of removal of life-sustaining therapies (e.g. removal of breathing

machines and drugs used to maintain blood pressure) so that death can be declared. For organ

donation to be successful, death must occur within 2 hours of removal of therapies. Currently,

there is a lot of variability in how clinicians withdraw life sustaining therapies, even for patients

who are not eligible for organ donation. This results in some clinicians feeling unsure about how

best to proceed when their patient is a potential donor and there are real or perceived pressures

about making sure donation is successful. This innovative project will use existing data collected

as part of a large, international, observational study of end of life care to explore whether, and

how processes of withdrawal of life sustaining therapies are different based on a patient’s status

as a potential donor. Our descriptions of what is currently occurring in clinical practice, and our

estimates of whether and how these differences influence donation outcomes such as time to

death will be useful for making future policies and providing guidance to healthcare providers.

The results of this study will help to create a culture of donation by informing the development

of best-practices for quality end-of-life care in the context of organ donation.

Dr Samantha Anthony

University of Toronto, SickKids, Toronto, ON

Study Title: inSight: Creation of an Electronic Patient-Reported Outcome Measure Platform in Pediatric Transplantation

New CDTRP study within Theme 5

Abstract :

Subjective evaluation of pediatric solid organ transplantation from the patient perspective is essential. Patient-reported outcome measures (PROMs) are vital to address the burden of disease and are defined as: “any report of the patient’s health condition that comes directly from the patient, without interpretation of the patient’s response by a clinician or anyone else”. PROMs can comprise information on symptoms, functional status, satisfaction, treatment adherence, well-being and quality of life. They have the ability to engage patients meaningfully, give them a voice in their healthcare, and capture their varied experience and attitudes. The overarching objective of this research program is to transform care delivery and improve health outcomes for pediatric solid organ transplant patients and families in Canada by implementing PROMs into practice. Building on our previously completed foundational research, the objective of the current proposal is to create an electronic PROM platform – inSight – to integrate PROMs systematically and effectively into practice. inSight will be created according to a user-centred agile software development model, that applies principles of iterative feedback, incremental development and continual stakeholder involvement. This research will inform future investigations including an implementation effectiveness evaluation of inSight and a national randomized trial to explore the impact of inSight on patient care and health outcomes in pediatric transplantation. The creation of inSight provides a unique opportunity to incorporate patient-centred data into clinical practice and represents an important step towards personalized healthcare. Without this research, the ideal methods to integrate PROMs into practice will remain unknown.

Dr Allan Murray

University of Alberta, Edmonton, AB

Study Title: Apelin receptor signaling and lymphocyte function in allograft rejection

New CDTRP study within Theme 3 and 4

Abstract :

The survival of solid-organ allografts (e.g. transplanted hearts or kidneys) is limited by chronic alloimmune responses against the graft. Among heart allograft recipients, for example, allo-immune injury of the coronary vasculature, centered around the vascular endothelial cells that line the blood vessels, is the leading cause of late graft loss. In recent work investigating the apelin receptor, we found receptor stimulation promotes healing of the injured endothelium. Treatment of mouse heart transplant recipients to stimulate the receptor markedly reduced the burden of vascular damage among the transplanted hearts. Remarkably, we found that the treatment also reduced the number of recipient immune cells in the heart transplant tissue. We have followed up on this surprising observation, and documented expression of the apelin receptor by immune cells in both the mouse and human. Our pilot experiments indicate stimulation of the apelin receptor on immune cells instructs the cells to ignore a cue that normally drives the immune cell to move from the blood into the tissue. This proposal will extend these observations. We will characterize apelin receptor expression among different immune cell subsets, and determine if apelin receptor stimulation blocks human immune cell movement across endothelial cells in cell culture. We will formally determine if apelin receptor stimulation alters the immune response to non-vascularized grafts. If we confirm apelin receptor stimulation has beneficial effects to promote repair of the transplant vasculature, and reduce immune cell responses to the graft, the findings may point to a new therapy to prolong graft survival.

Anne Halpin

University of Alberta, Edmonton, AB

Study Title: Knowing the unknown: adding an HLA-specific memory B cell assay to the toolbox

New CDTRP study within Theme 3 and 4

Abstract :

Organ transplantation saves the lives of patients with organ failure but their immune system will see the transplant as ‘foreign’ and try to reject it. Specific immune cells, called B cells, produce antibodies, Y shaped proteins that bind to their target. In transplantation, that target can be Human Leukocyte Antigens (or HLA) on the donor organ, resulting in serious damage and/or loss of the transplant. Antibody levels may decline over time, but B cells can form memory cells that promptly produce more antibodies when re-exposed to the foreign HLA. This is a crucial problem for transplant patients, particularly female patients who have been exposed to paternal (foreign) HLA during pregnancy.

Various tests are used to detect HLA antibodies in the patient’s blood to measure rejection risk. These tests, however, do not tell if the patient has memory B cells. The goal of this project is to develop a sensitive clinical test to detect memory B cells. We will ‘activate’ B cells isolated from blood and test to see if HLA antibodies are produced. We will compare cells from healthy females who have pregnancy HLA antibodies to females/males not exposed to foreign HLA. Next, we will compare memory B cells in female patients with known pregnancy-related HLA antibodies awaiting kidney transplant to those without antibodies. To check if blood is the best place to look for memory B cells, we will also test cells isolated from donor spleen, an organ where many B cells live. This assay has the potential to provide improved rejection risk assessment, help decide best recipient-donor matching, and guide the amount of anti-rejection drugs needed.

Dr James Shapiro

University of Alberta, Edmonton, AB

Study Title: Gene correction in human induced pluripotent stem cells from type-1 diabetic patients by CRISPR/Cas9 genome editing.

New CDTRP study within Theme 4

Abstract:

Islet transplantation shows clear evidence for replacing functional insulin producing (β-cells) and controlling autoimmunity in type-1 diabetic patients (T1DM). Despite the promise, islet transplantation has limitations as cell therapy for widespread T1DM population. Alternative approaches like induced pluripotent stem cells (iPSCs) offer new diabetes cell therapy. Human somatic cells reprogramed into iPSCs show clear proof-of-concept in generating renewable β-cells and in promoting personalized cellbased medicine for patients with diabetes. However, several investigations suggest that diabetic patient-derived iPSCs exhibit cellular reprograming complexities; genetic variation; and compromised β-cell differentiation compared to normal. This, in part, is due to genetic variants with unknown environmental triggers and interactions in immune modulatory and β-cell genes.

Preliminary studies have shown mutations in several β cell-specific and immune cell regulatory genes but very little is known about the impact of these genetic mutations on diabetes risk and progression. Henceforth, further research is required to identify critical genetic variants to understand the function and mechanism of these genetic determinants with T1D risk. In this exciting proposal, we aim to identify and screen putative genes in T1DM patient-derived iPSC lines versus healthy for effective genome editing tools. The goal is to create a library of genetic variants in β-cell-specific and immune modulatory genes and genetically correct the key genes to improve inter-/ intra-patient iPSC variability; consistent iPSC generation; efficient β-cell differentiation; and immune tolerance for preventing graft rejection. The approach thus provides a strategy to manufacture disease-free iPSCs for personalized cell-based therapy for type-1 diabetes.

Dr Diana Mager

University of Alberta, Edmonton, AB

Study Title: Biology of skeletal muscle and sarcopenia in children with ESLD awaiting LTx

New CDTRP study within Theme 5

Abstract:

Sarcopenia is a condition that is associated with reductions in skeletal muscle mass that can make it difficult for adults and children with liver cirrhosis to participate in activities of daily living. Adults with cirrhosis and sarcopenia also have an increased risk for more health problems (e.g rejection, lower quality of life) following a liver transplant (LTx). Recently our group has shown that sarcopenia is also common in children post-LTx and that it results in poorer growth and increased hospital readmission compared to children post-LTx without sarcopenia. Currently, little is known about the changes in muscle physiology that occur in adults and children with sarcopenia and liver disease. We need to understand this so we can develop effective treatment strategies to treat and prevent sarcopenia in children undergoing transplantations. The study purpose is to determine the prevalence of sarcopenia and the factors that influence the risk for children pre-and-post LTx getting this condition by studying Magnetic Resonance scans for body composition and reviewing medical information (e.g medications, lab work) from children’s medical records. We will also collect muscle biopsy samples when the LTx is being performed so we can also study the underlying physiological changes that occur in the muscles of children with and without sarcopenia. The ultimate goal of this project is to understand the factors that may contribute to pediatric LTx recipients developing sarcopenia, so we can develop effective rehabilitation interventions to treat sarcopenia and to contribute to the CDTRP’s vision of the One-Transplant for Life.

Dr Bethany Foster

McGill University, Montréal, QC

Study Title: Associations between Sex Hormone Levels and Immune Profiles among Kidney Transplant Recipients

New CDTRP study within Theme 4

Abstract :

Organ transplant recipients must take medications to suppress their immune systems for life. The way these immune suppressing medications are used varies little from patient to patient; regardless of sex or age, the approach is about the same. However, there are important sex and age differences in the immune system. We showed substantial sex differences in graft failure risk which depended on age: girls and young women show higher graft failure rates than boys and young men, whereas graft failure rates do not differ between women of post-menopausal age and men of the same age. This agedependent pattern of sex differences suggests that sex hormones may have an influence on the immune response. This study will gather preliminary data regarding the associations between sex hormone levels and the immune profile among 41 kidney transplant recipients (KTR) treated with immune suppressing medications and 40 healthy people. We will use advanced methods to identify different types of immune cells, their relative numbers, and their responses to stimulating agents, and ultrasensitive methods to measure blood sex hormone levels. We will then determine whether these measures of immune function are associated with sex hormone levels. This study may provide clues as to the biological reasons for higher graft failure rates in females compared with males. It will lead to future larger studies to develop personalized immunosuppression strategies, with the goal of developing personalized, age- and sex-specific immunosuppression strategies, and recommendations regarding the use of oral contraceptives and hormone replacement therapy, ultimately improving graft outcomes.

Drs Tania Jaudis-Ferreira and Marie-Chantal Fortin

McGill University and Université de Montréal, Montréal, QC

Study Title: Acceptability and feasibility of the Kidney Transplant Physical Activity and Social Club (KEeP ACTIVe Club)

New CDTRP study within Theme 5

Abstract :

Kidney transplant recipients face numerous challenges after transplantation. One of the challenges is the high frequency of diabetes, hypertension and heart disease. In addition, the majority of kidney transplant recipients face several barriers to engaging in and maintaining a good level of physical activity even years post-transplant which can increase the risk of mortality and developing poor organ function. They also experience feelings of isolation and loneliness after transplantation. The goal of this study is to develop the Kidney Transplant Physical Activity and Social Club” (KEeP ACTIVe Club) to offer support for kidney transplant recipients to improve their levels of physical activity, knowledge in risk factors for heart and circulatory diseases and break the isolation and loneliness after transplantation. Specifically, we aim to determine whether the KEeP ACTIVe Club is acceptable to kidney transplant recipients and feasible to be delivered and if participation in this club can increase levels of physical activity, knowledge in risk factors for heart and circulatory diseases and decrease socialization restrictions among kidney transplant recipients. We will offer participation in the KEeP ACTIVe Club for six months which consists of a face-to-face educational session about benefits of physical activity and risk factors for heart and circulatory diseases, online social networking (a Facebook closed group), peer and professional mentorship, and a menu of options for physical activities that patients can choose from based on their personal preferences. At the end of the study we will make recommendations for future versions of the KEeP ACTIVe Club.

Dr Karina Top

Dalhousie University, Halifax, NS

Study Title: Optimizing varicella immunization in children and youth with solid organ transplants to prevent disease and improve long-term health

New CDTRP study within Theme 5 and 4

Abstract :

Chickenpox, or varicella, was once a common and sometimes severe childhood illness. Due to effective vaccine programs, varicella is now uncommon, but outbreaks still occur. In children with weakened immune systems due to medications given after organ transplant, varicella can cause pneumonia, encephalitis (brain infection), and even death. Varicella vaccine contains a weak strain of the varicella virus; we have avoided the vaccine in children with transplants because of concerns that it could cause varicella. Studies now show that varicella vaccine is safe and effective in some of these children. Vaccine and transplant experts developed a guideline for determining which children with organ transplants could safely get the varicella vaccine. We plan to study how to use this guideline in transplant clinics to identify concerns that parents and healthcare providers have about varicella vaccination in children with transplants, and measure how the vaccine affects children’s quality of life. We will involve healthcare providers, children who received kidney, liver, and heart transplants at least one year ago and never received varicella vaccine, and parents. We will give children two doses of varicella vaccine three months apart and test their blood for varicella antibodies. We will monitor these children for vaccine adverse events (side effects) for one month and for chickenpox and shingles for six months. Parents will fill out surveys about their concerns about the varicella vaccine and how vaccination has affected their child’s life. The results will assist physicians in determining the best way to vaccinate children with organ transplants.

Dr. Tom Blydt-Hansen

University of British Columbia, Vancouver, BC

Study Title: Investigating serum immunometabolomic profiles associated with pediatric kidney and heart transplant alloimmune outcomes

New CDTRP study within Theme 5 and 4

Abstract :

Transplantation is the leading treatment for children diagnosed with end-stage organ failure. But beyond the first year after transplant, we know that some children will develop chronic forms of rejection that limits the transplant survival. We know that some people’s immune systems adapt better or become more “tolerant” to the transplant, but we don’t know all of the reasons. While medications are an important part, we also know that a person’s metabolism can play a role. That includes things like nutrition and disease, which can influence how a person’s immune system will respond. Under the right conditions, the immune system may be more likely to “adapt” to the transplant and avoid chronic rejection. This study will look at samples that have been collected before transplant, to see if there are changes that we can measure in metabolism that predict who will have a positive (adaptive) or negative (rejection) response to the transplant. We will test for hundreds of small molecules (called metabolites) that tell us about metabolism, in children who have had heart and kidney transplant. We will see how patterns of these metabolites might predict development of chronic forms of rejection, and how they are related to signs of a “tolerant” immune response. We hope that this research will help us in understanding what factors are high-risk for chronic rejection, and give us clues about how we can change them before transplant to improve chances for long-term transplant survival.

Dr Émmanuelle Brochiero

Université de Montréal

Study Title: From the donor to the recipient: Identification of novel biomarkers and therapeutic targets associated with primary graft dysfunction after lung transplantation

New CDTRP study within Theme 2 and 3

Abstract :

Lung transplantation is the only option for patients with terminal lung diseases such cystic fibrosis; however survival rates after lung transplantation still remain unacceptably low (~65% at 5 years). A phenomenon called primary graft dysfunction (PGD) is the major cause of death within 72h following transplantation and is also associated with lower long-term survival rates. It has been established that the cold preservation of the graft and blood reperfusion after lung engraftment cause ischemia/reperfusion injury (I/R), which is the primary cause of PGD. I/R is also characterized by an inflammation and liquid flooding in the lungs. Edema resorption is then highly dependent on alveolar epithelial integrity and function. However, our work revealed that key proteins of alveolar integrity/function are already dysregulated within the donor’s graft at the time of transplantation within recipient subsequently developing a PGD. Our hypothesis is that alveolar epithelial dysfunction is a critical component of PGD. Our aim is ideentify novel biomarkers of epithelial dysfunction in donor’s graft associated with PGD development in the recipient. To reach our goal, we will have access to clinical data from the donors and their recipients collected before, during and after lung transplantations as well as their samples, from which we will analyze the levels of various markers of epithelial integrity, damage and functionality. We are confident that our project will pave a way for the development of novel and personalized therapeutics approaches aimed at decreasing the impact of PGD and improving the survival of patients with lung transplantation.

Dr Mamatha Bhat

University of Toronto, University Health Network, Toronto, ON

Study Title: Development and Validation of a Practical Web-based Risk Calculator for Post-Transplant Diabetes using Machine learning

New CDTRP study within Theme 5

Abstract :

Short-term survival after solid organ transplantation (SOT) has improved over time, with advances in immunosuppression and post-transplant care. However, there have been no similar gains in long-term survival after transplant over the last 3 decades. The most common long-term complication across SOT is Post-transplant diabetes mellitus (PTDM), affecting up to 53% of SOT recipients. PTDM is associated with significantly decreased lifespan in the long term. Our goal for this project is to precisely predict which patients are at highest risk of PTDM, and which of those patients is at highest risk of death using artificial intelligence on a combination of clinical and biological information. We will develop a practical calculator that can be used by transplant physicians to identify patients at-risk, and will validate this calculator in real time as we see patients in the liver transplant clinic. Given that PTDM affects a large proportion of solid organ transplant patients (kidney, heart, lung, pancreas), the results of our study would provide the basis for evaluation across solid organ transplant groups. The ultimate goal is to develop more precise preventive and management strategies based on our study findings, in order to improve the long-term lifespan of liver transplant patients.

Dr Mingyao Liu

University of Toronto, University Health Network, Toronto, ON

Study Title: Cystic fibrosis and donor specific injuries in human lung transplants: a comprehensive bioinformatics and systems biology approach

New CDTRP study within Theme 3

Abstract :

Transplantation of lungs from cardiac death donors (DCD) in addition to donation after brain death (DBD) has become a method to address the global organ shortage. For the patients with Cystic Fibrosis (CF), whose lives depend on lung transplantation, the increase in the utilized donated lungs is of critical importance. Since the first lung transplant for a CF patient performed by the Toronto Lung Transplant team in 1988, there has been an increasing number of lungs transplanted to CF cases, with improved survival and quality of life. The inclusion of DCD donors has been made possible with the development of ex vivo lung perfusion (EVLP). Moreover, the survival of recipients receiving DBD or DCD donor lungs was shown to be similar. However, there is no clear understanding, besides clinical observation, of the transcriptional differences between the two groups of lungs. The objective of the proposed study is to perform a systematic bioinformatics and systems biology analysis on a large human data set of lungs from DBD and DCD donor groups and, within each group, between the lungs that were directly transplanted or were undergoing the EVLP system. We anticipate that by the end of this study we will gain a deeper understanding of the transcriptional signatures specific to each lung category and of the biological pathways that could be targeted with specific therapeutics to repair the lungs during the EVLP process, thus leading to increasing the pool of lungs for transplantation and reducing the CF patient waiting list and mortality.

Dr Michaël Chassé

Université de Montréal

Study Title: Early detection of potential organ donors using machine learning algorithms compared to traditional epidemiological approaches: Phase 1 of the COMPASS Network

New CDTRP study within Theme 1 and 2

Abstract :

Today, organ donation relies on clinicians for detection and referral of potential organ donors. Canadian studies show that we may be missing between 30% and 50% of potential donors. This project is a preliminary stage in developing a Canadian dOnation Monitoring & Alert SyStem Network (COMPASS) to improve potential organ donor identification processes. In the medical field, to make a prediction, we relied for decades on epidemiological approaches. Artificial intelligence has been shown to accomplish impressive feats outside of the medical field. It can learn from a massive amount of data how to predict certain events. However, it is not well known how those algorithms will be able to perform in the complicated medical field and how they compare to the time-tested ‘traditional’ approaches. Our goal is to use data available at a digital center called CITADEL (Centre d’IntégraTion et d’Analyse en DonnéEs MédicaLes du CHUM) and develop a system that could potentially detect automatically and in advance potential organ donors. We will be using two approaches: the first approach will use ‘traditional’ epidemiological strategies and a second approach using artificial intelligence. We will thus be able to 1) investigate if it is possible to develop accurate predictive/detection potential organ donor systems and 2) test if artificial intelligence can improve on ‘traditional’ approaches. We hope that our project will enable new ways to develop tools to help with the timely and accurate potential organ donor identification.

#researchcompetition #astellas #UHN #alberta #ATI #CRCHUM #pediatric #edmonton #montreal #crchum #TRFBC #kidneyfoundationofcanada #cysticfibrosiscanada

  • Black Facebook Icon
  • Black Twitter Icon
  • Black YouTube Icon

© 2014 by the CDTRP

All rights reserved