Renal transplantation using non-heart-beating donors: a potential solution to the organ donor shortage in Canada ================================================================================================================ * Julie D. Lacroix * John E. Mahoney * Greg A. Knoll ## Abstract **Introduction:** There is a chronic shortage of cadaveric organ donors for renal transplantation, which might be solved by the use of non-heart-beating donors (patients who suffer cardiac arrest and whose kidneys are harvested subsequently when irreversible heart and respiratory function occur). We carried out a chart review to determine whether the renal transplantation rate would improve if a non-heart-beating donor program was introduced at a Canadian centre. **Methods:** We reviewed the charts of all 1547 patients who died in the emergency department or intensive care unit of the Ottawa Hospital, a tertiary care centre serving 1.2 million people in eastern Ontario, between January 1999 and May 2001. The number of potential non-heart-beating donors was determined by the use of predefined criteria. The number of additional kidneys that could be obtained with a non-heart-beating donor program was estimated and compared to the actual number of kidneys procured from conventional brain-dead donors during the same period. The potential increase in the renal transplantation rate was calculated. **Results:** There were 83 potential non-heart-beating donors during the 29-month study period. The mean (and standard deviation) age of the donors was 40.6 (13.1) years, and 20% were female. The mean serum creatinine value was 75 (29) μmol/L; 44.6% of donors died secondary to trauma. We estimated that the use of non-heart-beating donors would have provided 14 to 41 additional donors during the study period (12–34 kidneys/yr). The cadaveric renal transplantation rate would have increased between 30% and 87%. **Conclusion:** The cadaveric renal transplantation rate could improve significantly if non-heart-beating donors were used in Canadian hospitals. The prevalence of end-stage renal disease (ESRD) has increased steadily since 1981.1 It has been estimated that 32 952 Canadians will need treatment for ESRD by 2005.2 The preferred treatment for ESRD is renal transplantation, which prolongs survival, enhances quality of life and is less costly than dialysis.3,4 Despite the demonstrated benefit of renal transplantation, only 41% of Canadians with ESRD have a functioning kidney transplant, and this proportion has gradually declined since 1988.1 This reflects the growing rate of ESRD and the relatively static number of cadaveric organ donors.1 Since 1989, the number of Canadians on a waiting list for a kidney transplant has more than doubled, 1 but the number of cadaveric kidneys transplanted has remained essentially unchanged.1 A potential solution to the cadaveric donor shortage is the use of non-heart-beating organ donors.5 A non-heart-beating donor is defined as one who first sustains cardiorespiratory arrest; organs are retrieved after irreversible cessation of cardiac and respiratory function.6 Death in this case is based on cardiac criteria.6 In contrast, a conventional heart-beating donor is one who sustains irreversible brain injury, and death is based on neurologic criteria.6 The concept of non-heart-beating organ donation is not new. In the early days of transplantation all cadaveric donors were non-heart-beating, as there were no laws governing brain death.7 Once the concept of brain death was established, the use of non-heart-beating donors decreased significantly. Four categories of non-heart-beating donors have been identified as follows: category 1 — dead on arrival at the hospital; category 2 — unsuccessful resuscitation; category 3 — awaiting cardiac arrest; category 4 — cardiac arrest while brain dead (Table 1).6 Donors from categories 1, 2 and 4 have also been classified as uncontrolled donors because cardiac arrest occurs spontaneously without warning.8 Category 3 donors have been classified as controlled donors because cardiac arrest only occurs after support is withdrawn.8 View this table: [Table 1](http://canjsurg.ca/content/47/1/10/T1) Table 1 Categories of Non-Heart-Beating Donors The results using non-heart-beating donors for kidney transplantation have been encouraging. Recent data from the United States have shown that recipients of a non-heart-beating donor kidney have a 5-year renal allograft survival that is the same as those who received a conventional heart-beating donor kidney.9 In a study from the United Kingdom, Nicholson and colleagues10 showed that recipients of non-heart-beating and heart-beating cadaveric donor kidneys had similar 5-year renal allograft survival rates. An even more impressive finding was that the non-heart-beating donor kidneys had a 5-year allograft survival rate that was not significantly different from recipients of a living donor kidney.10 Weber and colleagues11 have recently reported long-term results using non-heart-beating donors in Switzerland. Using a matched-pair analysis, they showed that kidney-graft survival 10 years after transplantation was 78.7% for kidneys from a non-heart-beating donor and 76.7% for kidneys from a conventional heart-beating donor. Two studies have examined the potential impact of non-heart-beating organ donation in Canada.8,12 Taylor and colleagues12 demonstrated that the introduction of a non-heart-beating donor program would have the greatest opportunity to increase the cadaveric organ pool. However, they included donors up to the age of 80 years, which is generally not recommended for non-heart-beating donation. 10 Campbell and Sutherland8 showed that a non-heart-beating donor program would have increased their cadaveric renal transplantation rate by 48%. However, they only analyzed controlled non-heart-beating donors and once again included older donors (64% > 65 yr).8 Given that a non-heart-beating organ donor program may generate a substantial workload,13 we wanted to estimate the full impact that such a program would have if it was introduced at a Canadian hospital. The specific objective of this study was to determine how many additional kidneys could be transplanted at a Canadian centre if such a program were introduced. We chose to study both controlled and uncontrolled non-heart-beating donors since previous reports have shown the greatest potential from uncontrolled donors.6,10 In addition, we limited our analysis to donors 60 years of age or younger since there is a high failure rate with older non-heart-beating donors.10 ## Methods We used the health records database of the Ottawa Hospital to identify all patient deaths that occurred in the intensive care unit or the emergency department of the Ottawa Hospital between Jan. 1, 1999, and May 31, 2001 (29-month study period). The Ottawa Hospital is a 1047-bed tertiary care facility with 65 critical care beds serving approximately 1.2 million people in eastern Ontario. The study was approved by the Ottawa Hospital Research Ethics Board. Patient records were reviewed to determine if there were any contraindications to non-heart-beating organ donation. Patients were excluded from the analysis if any of the following were present: age less than 16 years or more than 60 years; a known history of malignant disease, renal disease, diabetes or hypertension; documented history of hepatitis B, hepatitis C or HIV infection; history of intravenous drug use; sepsis during hospitalization; a conventional (brain dead) heart-beating donor; a brain dead potential heart-beating donor but consent declined by coroner or family; or a serum creatinine level greater than 125 μmol/L. All remaining patients were considered potential non-heart-beating donors and included in the analysis. The following data were abstracted from the charts of all potential non-heart-beating donors: age, gender, cause of death, location of death and serum creatinine value. Using the methods of Daemen and associates,14 we made a low, moderate and high projection of the number of additional kidneys that could be transplanted if a non-heart-beating donor program were in place. The low projection was a conservative estimate that included only controlled (category 3) donors. The moderate estimate, which is the protocol in Leicester (UK)10 and Zurich,11 included categories 2, 3 and 4. The high estimate included all categories of donors and is the protocol in many Spanish centres.15 We assumed that consent for organ donation would be obtained in 75%. This value represents the average of actual consent rates obtained from existing non-heart-beating organ donor programs.13,14,16 We assumed that 40% of category 1, 2 and 4 donor organs13–15 and 15% of category 3 donor organs8,15 would not be suitable for transplantation because of poor renal function, prolonged ischemia, renal trauma, renal damage on biopsy or technical problems during organ perfusion and procurement. During the same time period of this study, we obtained data on the number of heart-beating donors at our institution. These findings were used to compare the potential number of kidneys obtained from a non-heart-beating program to the actual number of kidneys obtained from conventional heart-beating donors. ## Results During the study period, 1547 patients died in the emergency department or the intensive care unit; 83 (5.4%) did not have any exclusion criteria and were considered potential non-heart-beating donors. The majority of the patients were male and the average age was 40.6 years (Table 2). Most of the patients died in the emergency department as a result of trauma (Table 2). View this table: [Table 2](http://canjsurg.ca/content/47/1/10/T2) Table 2 Characteristics of the 83 Potential Non-Heart-Beating Donors Patients dead on arrival at the emergency department (category 1) accounted for 28% of the cases (Table 3). Controlled donors (category 3) accounted for 26%, and the remaining 74% were uncontrolled donors (categories 1, 2 and 4). The most common source of potential non-heart-beating donor kidneys was from patients who died after unsuccessful resuscitation (category 2), accounting for 44% of all cases. The cause of death was unknown for 48% of category 1 donors (Table 3). In the other 3 categories, trauma was the commonest cause of death (Table 3). View this table: [Table 3](http://canjsurg.ca/content/47/1/10/T3) Table 3 Categories of Potential Non-Heart-Beating Donors We estimate that a non-heart-beating organ donor program would have resulted in an additional 28 to 82 kidney transplants during the study period (Table 4). This translates into an additional 12 to 34 kidney transplants per year. During the study period there were 47 actual heart-beating organ donors leading to 94 kidney transplants. A non-heart-beating donor program would have increased our cadaveric renal transplantation rate by 30% to 87%. View this table: [Table 4](http://canjsurg.ca/content/47/1/10/T4) Table 4 Projected Number of Non-Heart-Beating Donors* ## Discussion One of the greatest problems facing organ transplantation is the lack of donors with an ever-increasing number of potential recipients. Without a substantial increase in the number of donor organs, relatively fewer Canadians will enjoy the benefits of transplantation. This analysis demonstrated that a non-heart-beating organ donor program would significantly increase the number of cadaveric kidneys available for transplantation at a Canadian hospital. These findings are consistent with previous studies on non-heart-beating organ donation. With the use of non-heart-beating donors, the cadaveric renal transplantation rate increased by 27% in a Spanish hospital,15 34% in a British hospital10 and 66% at a transplant centre in the Netherlands.17 Our projected increase was 30% to 87%. Campbell and Sutherland8 showed that the renal transplantation rate would have increased by 48% in Calgary using only controlled non-heart-beating donors. From 1989 to 1999 an average of 700 cadaveric kidneys were transplanted annually in Canada, while the number of patients waiting for a kidney transplant increased from 1386 to 2808.1 If the results of our study were applied nationally an additional 210 to 610 kidneys annually would be available for transplantation. Such an increase in the cadaveric donor pool would help slow down the growth in the renal wait list1 and likely decrease the waiting time to transplantation. A decrease in waiting time would not only improve the quality of life for patients with ESRD but may also improve survival after kidney transplantation.18 At the request of the United States Department of Health and Human Services, the Institute of Medicine conducted an exhaustive review of non-heart-beating organ transplantation. The report, published in 1997, concluded that “the recovery of organs from non-heart-beating donors is an important, medically effective, and ethically acceptable approach to reducing the gap that exists now and will exist in the future between the demand for and the available supply of organs for transplantation.”19 The report suggested principles that should be followed in non-heart-beating organ donation, the most important of which included the commitment to informed consent, respect for donor and family wishes and the creation of locally approved protocols that are open to the general public.19 Since the release of this report, the number of kidneys transplanted from non-heart-beating donors has increased annually in the US.20,21 In 2001, surgeons in 68 hospitals in the US transplanted at least 1 kidney from a non-heart-beating donor.21 Non-heart-beating organ donation tends to occur in a time-pressured environment. Each step in the process from donor identification to procurement must occur within a certain period to minimize warm ischemia to the kidneys.22 After death is declared, a special catheter is inserted into the femoral artery to perfuse the kidneys with cold preservation fluid.22 Once in situ perfusion has been completed, the donor is transported to the operating room. The donor nephrectomy should be completed within 2 hours of in situ perfusion.22 Given the current economic restraints in most Canadian hospitals, non-heart-beating organ donation could not proceed without significant changes. Additional resources would be needed to staff a special operating room that would be available for urgent donor procedures. Given that it costs approximately $74 000 per year to keep 1 patient alive on hemodialysis,23 the costs to set-up and operate a non-heart-beating donor program should be quickly recovered. Bibo and associates24 showed that the use of non-heart-beating donors for kidney transplantation was as cost-effective as conventional heart-beating donors and more cost-effective than dialysis. What is the best way to proceed with non-heart-beating donation in Canada? Although many western countries9,10,15 already use both controlled and uncontrolled non-heart-beating donors, we recommend gradual introduction in Canada. From a logistical point of view, it would be easiest to start with controlled (category 3) donors. Once a controlled non-heart-beating donor program has been established, expansion could include categories 2 and 4 donors. Category 1 donors, although successfully used in Spain,15 would likely be introduced in Canada only after several years’ experience with the other types of non-heart-beating donors. The strengths of this study include a large number of patient deaths evaluated, a predefined set of exclusion criteria applied consistently and the use of conservative exclusion criteria (e.g., age > 60 yr) that would not overestimate our results. However, the study also has limitations. We assumed that family consent for non-heart-beating donation would be 75%, the same as our current consent rate for heart-beating donors. Conceivably, the consent rate for organ donation after an unexpected cardiac arrest would not be optimal. However, Daemen and associates14 have reported equal consent rates for heart-beating and non-heart-beating organ donation. Alvarez and Rosario del Barrio16 reported a higher consent rate for non-heart-beating than for heart-beating donors. Nicholson and associates13 have reported a 72% consent rate in their non-heart-beating donor program. A substantial number of category 1 donors died of unknown causes and likely would not be used. However, even when these were excluded (Table 4), a significant number of kidneys were available for transplantation. ## Conclusions At a Canadian centre, we have shown that the cadaveric renal transplantation rate could improve significantly with the use of a non-heart-beating donor program. We believe it is time for Canadian centres to move forward in this area and begin developing such programs. With the implementation of properly designed protocols, Canada could significantly increase its organ donor rate and improve the quality of life for Canadians with end-stage renal failure. ## Acknowledgements Ms. Lacroix completed this project during a summer research studentship with the University of Ottawa Faculty of Medicine. Salary support was provided by the Burroughs Wellcome Fund Student Research Awards of the Canadian Institutes of Health Research and the University of Ottawa Division of Urology Research Fund. ## Footnotes * **Competing interests:** None declared. * Accepted April 29, 2003. ## References 1. 2001 Report, volume 1: Dialysis and renal transplantation, Canadian Organ Replacement Register. Ottawa: Canadian Institute for Health Information; 2001. 2. Schaubel DE, Morrison HI, Desmeules M, Parsons D, Fenton S. End-stage renal disease in Canada: prevalence projections to 2005. CMAJ 1999;160:1557–63. [Abstract/FREE Full Text](http://canjsurg.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6NDoiY21haiI7czo1OiJyZXNpZCI7czoxMToiMTYwLzExLzE1NTciO3M6NDoiYXRvbSI7czoxNzoiL2Nqcy80Ny8xLzEwLmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==) 3. Schnuelle P, Lorenz D, Trede M, Van der Woude FJ. 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