Correspondence
Kidney Transplantation from Donors without a Heartbeat
N Engl J Med 2002; 347:1799-1801November 28, 2002
- Article
To the Editor:
The report by Weber et al. (July 25 issue)1 provides persuasive evidence that kidneys from donors without a heartbeat can be transplanted with satisfactory long-term results. However, the impact of this source of donor organs remains subject to speculation. Studies suggest that the increase in the overall number of kidneys from donors per year could range from 11 percent to as much as 350 percent.2,3
In 2001, the United Network for Organ Sharing reported that there were 6081 cadaveric donors in the United States. The Association of Organ Procurement Organizations recently concluded that between 11,000 and 14,000 cadaveric donors may potentially be available each year. A review of all studies published since 1975 that assessed the size of the potential donor pool suggests that as many as 19,100 cadaveric donors may be available each year.
In 2000, approximately 64,000 patients were on the waiting list for a kidney transplant at some point during the year, but only 13,372 received transplants. However, it is almost certain that the demand for kidney transplantation is a relatively poor indicator of true need.4 In 2000, 56 percent of patients undergoing dialysis (154,905) were under the age of 65 years, and 45 percent (124,677) were under the age of 60.5
Table 1Table 1
Increase in the Overall Supply of Kidneys According to Four Assumptions. shows the increases in the number of kidneys that might be available each year, on the basis of published reports. Clearly, kidneys from donors without a heartbeat could have a substantial role in meeting the demand, as well as the potential need, for kidney transplantation. Moreover, when kidneys from donors without a heartbeat are combined with kidneys from cadaveric donors, it is conceivable that the shortage of donors could be eliminated within five years.5 ReferencesRoger W. Evans, Ph.D.
2251 Baihly Hills Dr. SW, Rochester, MN 55902
evans.roger@charter. net 1
Weber M ,Dindo D ,Demartines N ,Ambuhl PM ,Clavien P-A . Kidney transplantation from donors without a heartbeat. N Engl J Med 2002;347:248-255
Full Text | Web of Science | Medline2
Cho YW ,Terasaki PI ,Cecka JM ,Gjertson DW . Transplantation of kidneys from donors whose hearts have stopped beating. N Engl J Med 1998;338:221-225
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Cecka JM . Donors without a heartbeat. N Engl J Med 2002;347:281-283
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Evans RW . Need, demand, and supply in kidney transplantation: a review of the data, an examination of the issues, and projections through the year 2000. Semin Nephrol 1992;12:234-255
Web of Science | Medline5
Renal Data System. USRDS 2002 annual data report: atlas of end-stage renal disease in the United States. Bethesda, Md.: National Institute of Diabetes and Digestive and Kidney Diseases, 2002.
To the Editor:
A significantly larger proportion of donors with a heartbeat than of those without a heartbeat had a cerebrovascular event as the cause of death, which is also associated with worse graft survival. Although Weber et al. report that the cause of death did not have a significant influence on graft survival, they do not provide the P value, and the nonsignificant result may have been due to the small number of grafts lost in each group. Moreover, immunosuppressive therapy was optimized only for the group that received kidneys from donors without a heartbeat — that is, all recipients of organs from donors without a heartbeat received sequential therapy with antithymocyte globulin and delayed administration of cyclosporine. Delayed graft function results from ischemic injury of the graft, which up-regulates the expression of HLA, causes the production of inflammatory cytokines, and consequently increases the immunogenicity of the graft. It has recently been demonstrated that T cells — more specifically, CD4+ T cells — are implicated in ischemia–reperfusion damage,1 which can have long-term consequences for graft function and survival.
As the authors comment, the use of antithymocyte antibody might have attenuated ischemia–reperfusion injury,2 which, in association with cyclosporine nephrotoxicity, can delay the recovery of renal function and decrease graft survival. As a matter of fact, only in recipients of grafts from donors with a heartbeat was delayed graft function a risk factor for graft failure (hazard ratio, 2.9; P=0.03). Thus, the recipients of grafts from donors with a heartbeat might have benefited from the same immunosuppressive protocol used for recipients of grafts from donors without a heartbeat and might have had even better graft survival.
2 ReferencesAna Cristina Carvalho de Matos, M.D.
Universidade Federal de São Paulo, 04023-900 São Paulo, BrazilMarcelino Souza Durão, M.D.
Hospital Israelita Albert Einstein, 05651-901 São Paulo, BrazilAlvaro Pacheco-Silva, M.D.
Universidade Federal de São Paulo, 04023-900 São Paulo, Brazil
apacheco@nefro.epm. br 1
Burne MJ ,Daniels F ,El Ghandour A , et al. Identification of the CD4(+) T cell as a major pathogenic factor in ischemic acute renal failure. J Clin Invest 2001;108:1283-1290
CrossRef | Web of Science | Medline2
Shoskes DA ,Cecka JM . Deleterious effects of delayed graft function in cadaveric renal transplant recipients independent of acute rejection. Transplantation 1998;66:1697-1701
CrossRef | Web of Science | Medline
To the Editor:
When Weber et al. used univariate analysis to look for risk factors associated with poor long-term survival, they found that delayed graft function was not a risk factor and concluded that delayed graft function did not have a significant negative effect on long-term graft survival in recipients of grafts from donors without a heartbeat. I believe that conclusion is misleading for two reasons. First, recipients with delayed graft function and those without delayed graft function should have been compared within each group in order to determine the effect of delayed graft function on the survival of grafts. Second, the use of thymoglobulin induction with the delayed introduction of cyclosporine certainly must have contributed to the equivalent long-term outcome in the two groups, as suggested by the observation that, despite a higher rate of delayed graft function in the group that received kidneys from donors without a heartbeat, the rate of acute rejection did not differ significantly between the two groups. The fact that the rate of acute rejection was higher, despite thymoglobulin induction, than the rates reported previously in the literature1 suggests that a higher rate of delayed graft function did have an effect on the incidence of acute rejection. Had Weber et al. not used such a protocol, long-term graft survival would have been negatively affected.
1 ReferencesFu L. Luan, M.D.
University of Michigan Health System, Ann Arbor, MI 48109-0704
fluan@umich.edu 1
Brennan DC ,Flavin K ,Lowell JA , et al. A randomized, double-blinded comparison of Thymoglobulin versus Atgam for induction immunosuppressive therapy in adult renal transplant recipients. Transplantation 1999;67:1011-1018[Erratum, Transplantation 1999;67:1386.]
CrossRef | Web of Science | Medline
To the Editor:
In the study by Weber et al., the incidence of delayed graft function was higher in the group with grafts from donors without a heartbeat than in the group with grafts from donors with a heartbeat, but the rate of long-term graft survival was remarkably similar in the two groups.
My colleagues and I designed a double-balloon, triple-lumen catheter (the García Lefrak catheter) that is inserted through a femoral artery into a cadaver at the precise moment of cessation of the heartbeat.1 With proper preconditioning of the donor and the infusion of cold crystalloid solution into the partitioned aortic segment where the renal arteries arise, excellent in situ cooling of the kidney can be achieved.1 In situ cooling provides additional time to perform the nephrectomy in the donor, with minimal ischemia time. Such an approach may be an important adjunct because Weber et al. report that after 1995, organ retrieval began 10 minutes after cardiopulmonary arrest — a substantial amount of warm-ischemia time.
1 ReferencesRaúl García-Rinaldi, M.D.
Advanced Cardiology Center, Mayaguez, PR 00681-6684
garciarinald@prtc.net 1
Garcia-Rinaldi R ,Lefrak EA ,Defore WW , et al. In situ preservation of cadaver kidneys for transplantation: laboratory observations and clinical application. Ann Surg 1975;182:576-584
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Author/Editor Response
The authors reply:
To the Editor: The number of available donors without a heartbeat remains speculative and depends on many factors. Although we agree with Dr. Evans that an 11 percent increase in donation, as observed in our program,1 may represent a conservative figure, it remains to be seen whether optimizing this source of organs will solve the shortage of available kidneys within five years.2 This could, however, represent a stimulating goal in many countries.
The double-balloon catheter system proposed by García-Rinaldi might well improve the preservation of kidneys, but an important factor influencing the wide acceptance of donors without a heartbeat is the simplicity of the procedure and ethical situation. We have shown excellent results with a simple technique without the use of in situ cooling.1 Manipulation of a donor before or at the time of cessation of the heartbeat may raise ethical questions.3
Dr. Luan challenges our finding that delayed graft function had no negative effects on long-term graft survival in recipients of kidneys from donors without a heartbeat. Contrary to his statement, we performed multivariate, logistic-regression analyses separately for donors with a heartbeat and those without a heartbeat, which showed a negative effect on the long-term outcome in grafts from donors with a heartbeat (but not in grafts from donors without a heartbeat). Regarding Dr. Luan's second point, our data showed no correlation between delayed graft function and acute rejection in grafts from donors without a heartbeat. The point about the potential benefit of thymoglobulin is discussed below.
Carvalho de Matos et al. correctly point out that the regimen of antithymocyte globulin and delayed administration of cyclosporine was routinely used only in recipients of kidneys from donors without a heartbeat and has certainly contributed to the excellent outcome in these patients. The same regimen was used in recipients of grafts from donors with a heartbeat in the presence of delayed graft function. This does not detract from the main message of the study — that an excellent long-term outcome can be achieved with kidney grafts from donors without a heartbeat.
3 ReferencesMarkus Weber, M.D.
Daniel Dindo, M.D.
Pierre-Alain Clavien, M.D., Ph.D.
University Hospital Zurich, CH-8091 Zurich, Switzerland
clavien@chir.unizh. ch 1
Weber M ,Dindo D ,Demartines N ,Ambuhl PM ,Clavien P-A . Kidney transplantation from donors without a heartbeat. N Engl J Med 2002;347:248-255
Full Text | Web of Science | Medline2
Cecka MJ . Donors without a heartbeat. N Engl J Med 2002;347:281-283
Full Text | Web of Science | Medline3
Vanrenterghem Y . Cautious approach to use of non-heart-beating donors. Lancet 2000;356:528-528
CrossRef | Web of Science | Medline
- Citing Articles (4)
Citing Articles
1
Gary S Becker, Julio Jorge Elías. (2007) Introducing Incentives in the Market for Live and Cadaveric Organ Donations. Journal of Economic Perspectives 21:3, 3-24
CrossRef2
J. E. Locke, D. L. Segev, D. S. Warren, F. Dominici, C. E. Simpkins, R. A. Montgomery. (2007) Outcomes of Kidneys from Donors After Cardiac Death: Implications for Allocation and Preservation. American Journal of Transplantation 7:7, 1797-1807
CrossRef3
Peter Abt, Randeep Kashyap, Mark Orloff, Ashok Jain, George Tsoulfas, Adel Bozorgzadeh, Kim Olthoff. (2006) Pediatric Liver and Kidney Transplantation With Allografts From DCD Donors: A Review of UNOS Data. Transplantation 82:12, 1708-1711
CrossRef4
Richard J. Howard, Jesse D. Schold, Danielle L. Cornell. (2005) A 10-year Analysis of Organ Donation after Cardiac Death in the United States. Transplantation 80:5, 564-568
CrossRef
