Organ Donation and Transplantation

Canada is the second-largest country in the world with its relatively small population (approximately 35 million) divided into 10 provinces and 3 territories. Administration and delivery of healthcare services in Canada, including donation and transplantation, is complex with national legislation (Canada Health Act, 1984) but with actual delivery of health care being a provincial/territorial responsibility. The Canada Health Act enforces universal access to care for hospital and physician services for all residents without charge.1 However, coverage for other aspects of care (eg, prescription drugs, ambulance services, home care, and so on) varies regionally. Rather than a “national healthcare system,” there are 10 provincial and 3 territorial systems administered by 13 separate Ministries of Health.2 Approximately 70% of all healthcare costs are covered by the government with the remaining 30% covered privately (50% out-of-pocket by the patient and 50% private supplemental insurance).1 DECEASED ORGAN DONATION Organ donation and transplantation in Canada continues to evolve against this backdrop. No single national agency is responsible for organ donation or transplantation services. Eleven different deceased donor organizations, each with unique policies, procedures and budgets, manage deceased donation.3 Historically, Canada's deceased donor rate has fluctuated between 12 and 14 per million population (PMP), lower than high-performing countries with national donation organizations, such as Spain and the United States.4 Recently, rates have increased annually from 13.7 PMP in 2010 to 15.7 PMP in 2013.4 Despite this overall progress, high variability in donor activity from region to region has limited maximum system-wide improvement. In 2013, the deceased donor rate varied from 7.2 to 20.2 PMP between different regions in Canada (Figure 1).4FIGURE 1: Deceased organ donor rate (PMP) by region in Canada. Atlantic includes New Brunswick, Nova Scotia, Prince Edward Island, and Newfoundland and Labrador. Reprinted with permission from Canadian Institute for Health Information. Canadian Organ Replacement Register Annual Report: Treatment of End-Stage Organ Failure in Canada, 2004 to 2013, Ottawa, ON: CIHI; 2015.4The source of this variability is multifactorial. Deceased donation activity is resource intensive, competing with other provincial priorities and donation funding differs between regions. Furthermore, responsibility for donation outcomes is ill-defined with neither individual physicians nor hospitals held accountable for poor performance. Even more informative are variations in clinical practice with respect to the uptake of donation after cardiocirculatory death (DCD) and the use of older donors. Beginning in 2006 through to 2012, there were 225 DCD donors in the province of Ontario, 37 in Quebec and 21 in British Columbia but only 6 DCD donors in Alberta and none reported in Saskatchewan, Manitoba, New Brunswick, Prince Edward Island or Newfoundland (Figure 2).5,6 In 2012, DCD accounted for 24% of all deceased organ donors in Ontario while still unutilized in 5 provinces despite national recommendations.5-7 Similarly, utilization of older donors varies substantially between regions. In a recent analysis, donors older than 60 years accounted for only 9% of all deceased donors in the provinces of Alberta and Manitoba compared to 34% in Quebec.5 Comparatively, 45% of deceased donors in Spain in 2009 were 60 years or older.5 Adoption of best practices from high-performing regions could have an immediate and dramatic impact on donation in Canada.FIGURE 2: Donation after cardiocirculatory death as a proportion of total deceased donors by region in Canada. Reprinted from Deceased Organ Donation Potential in Canada, The Canadian Institute for Health Information, Dec 18, 2014.5A CHANGING LANDSCAPE Although there is still no single national donation/transplantation agency in Canada, the federal, provincial, and territorial governments identified a need for improvement, requesting that Canadian Blood Services assume specific interprovincial roles for establishing leading practices, professional and public education, system reporting and interprovincial listing and allocation beginning in 2008. The Canadian Transplant Registry was developed supporting 3 patient programs: Kidney Paired Donation (KPD), the National Organ Waitlist, and the Highly Sensitized Patient (HSP) program. In 2009, the Canadian KPD program was launched to facilitate kidney transplantation for patients with a willing but (ABO and/or HLA) incompatible living donor. Since inception through 2013, 271 kidney transplants have been completed involving patients from all provinces.8,9 Although more difficult to match in paired donation, 100 blood type O candidates and 35 patients with a calculated panel-reactive antibody (cPRA) level of 95% or higher have been transplanted.9 In addition, 54 nondirected anonymous donors have resulted in 53 waitlisted patients receiving a transplant.9 The success of this program is based on several factors: (i) a high degree of collaboration and trust between the participating transplant centers, (ii) use of standardized antibody testing and a comprehensive HLA typing and antibody data management system encompassing all HLA loci (<2% unexpected positive flow crossmatches since 2012), (iii) standardized work-up and acceptance criteria for living donors, (iv) utilization of a centralized allocation software system, and (v) travel and logistics support provided by the provincial governments.8,9 The KPD program has resulted in 271 transplants that either would not have occurred or would have proceeded with substantially higher immunologic risk. As a consequence, there are fewer patients on the deceased donor waitlist, better long-term outcomes for recipients are anticipated and the time to transplant has been shortened for those without a living donor. The National Organ Waitlist was launched in 2012 and includes clinical information on all patients with non-renal end-stage organ failure awaiting transplantation. This online registry contains real-time data necessary to facilitate interprovincial organ sharing. Before the establishment of this registry, data were maintained by 1 transplant center with information shared by weekly fax distribution. Going forward, the registry will list all candidates waiting for transplant. As a result, the Canadian Transplant Registry will also be the cornerstone for the evolving data and analytics service to inform both system reporting and ongoing research. The HSP Program, identifying acceptably mismatched donor kidneys for patients with cPRA of 95% or higher, launched in October 2013 in a few provinces, with complete national participation by November 2014. Before this program, kidneys were only rarely shared between provinces. Now, for every available donor in Canada, 1 kidney is offered for sharing if a suitable HSP recipient is identified with a negative virtual cross match. To date, 125 highly sensitized patients have been transplanted in 10 different provinces (personal communication, Kimberly Young, Canadian Blood Services). Unexpected positive flow crossmatches after organ shipping have been rare (<2% to date) due to accurate cPRA estimation with the Canadian cPRA calculator combined with complete HLA typing of donors and recipients across all loci including DP.10 Together, these 3 new programs are linking donors and recipients in a unique fashion that is facilitating transplantation for Canadians with previously significantly diminished access. RESEARCH TO IMPROVE CANADIAN ORGAN DONATION AND TRANSPLANTATION In 2012, the Canadian Institutes of Health Research, the national funding agency for health research, presented the transplant community with a challenge: to bring the solid organ transplant, hematopoietic cell transplant, and donation research communities together into a national research program that would transform the field of transplantation and improve the health of Canadians. The research community responded to this challenge by building a national program that is not only innovative and unique in Canada but also in the world. The Canadian National Transplant Research Program (CNTRP) is a nationally funded research network charged to develop new knowledge and healthcare practices to increase the availability of transplants while enhancing outcomes and quality of life of transplant recipients. The CNTRP unites over 100 researchers, collaborators, and trainees from 29 universities and institutions across Canada representing basic and clinical scientists in organ donation/critical care, hematopoietic cell transplantation, liver, heart, lung, pancreas, and kidney transplantation, as well as health economics, legal and ethics researchers, policy experts and knowledge users into a dynamic, integrated research coalition. The CNTRP is a uniquely Canadian initiative, which draws on our strength in scientific collaboration, our history of transplantation research, and our publicly funded healthcare system. The CNTRP research framework is innovative and transdisciplinary integrating 6 projects and 3 comprehensive supporting cores: Project 1: Ex vivo organ transplant protection and repair Project 2: Increasing solid organ and hematopoietic cell donation Project 3: Understanding/preventing early graft rejection and graft versus host disease Project 4: Strategies for immunomodulation and transplant tolerance Project 5: Predicting and controlling viral complications of transplantation Project 6: Improving pediatric outcomes in transplantation Core 1: Ethical, economic, legal, and social platform Core 2: Research infrastructure and registries support platform Core 3: Training and career development platform The CNTRP Training and Career Development platform leverages national cross-disciplinary opportunities, fostering a new generation of interrelated transplant researchers. Integrated knowledge translation strategies are multidirectional, embracing a wide range of stakeholders. The CNTRP positions Canada as a world leader in transplantation research, creating an enduring legacy that will transform the field of transplantation in Canada. CONCLUSIONS The coordination of donation/transplantation services in Canada is complex due to our large geography and legislated mandates on healthcare delivery. Historically, deceased organ donation performance has been suboptimal. Recent improvements are encouraging but more work is needed to achieve metrics of high-performing countries. National programs supported through the Canadian Transplant Registry are allowing greater benefits from transplantation. An innovative national research program has been recently established addressing major unmet needs and holds promise to improve many aspects of donation and transplantation care in Canada and worldwide. ACKNOWLEDGMENTS Canadian Blood Services' mandate is funded by Canadian Federal, Provincial and Territorial Governments (excluding Quebec) and the opinions stated herein are not those of the Federal, Provincial and Territorial Governments.

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