Grant: Genomics and Personalized Health -Large-Scale Applied Genomics Res Projects

Chronic kidney disease affects 1 in 10 Canadians with estimated costs of over $2 billion/year. Transplantation is the treatment of choice for those whose kidneys fail: it improves survival (>85% vs <50% at 5yr), optimizes quality of life (85% vs 70% of normal) and decreases health-care costs ($15,000 vs $55,000/yr) compared with dialysis. But severe graft rejection (known as “antibody-mediated” rejection or AMR) occurs in up to 30% of transplant patients causing premature graft loss, return to dialysis, and early death. We will develop a program to prevent AMR and promote lifetime survival of the transplanted kidney. Our program will employ genetic technologies to: (a) reduce the risk of rejection through better donor-patient matching; (b) monitor the immune response after transplant to predict AMR; (c) enable personalized treatment with powerful drugs to prevent rejection while avoiding infection or cancer; and (d) study the legal, ethical, societal and economic considerations of introducing these strategies into clinical practice to improve quality of life and reduce health-care costs. The program builds on our highly successful national transplant program coordinated through the Canadian Blood Services (CBS) and links 16 major transplant programs, 9 leading universities, and 14 provincial transplant organizations and laboratories. It is led by an experienced Canadian and international team of genome experts, transplant immunologists, clinical scientists, legal scholars, ethicists, and health economists, working collaboratively with patients, members of the public, health providers, provincial health organizations, national coordinating bodies and commercial partners. Our program seeks to reduce the frequency of AMR by at least 50%, with the expected benefits from preventing rejection commencing quickly and increasing annually due to increased survival of transplanted kidneys. Approximately 500 Canadian patients lose their graft every year, and return to dialysis results in a 4-fold increase in the risk of death, decreased quality-of-life and incremental costs of up to $1 million per patient over their remaining life years. The benefits of this program will consequently occur at three levels: (a) the patient and family, with a gain in survival and quality of life, reduced caregiver burden, and personal health expenditures; (b) the healthcare system, with reduced dialysis care and re-transplant needs; (c) and society, due to increased workforce productivity and decreased kidney management costs.