Changing the Priority for HLA Matching in Kidney Transplantation
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《新英格兰医药杂志》
To the Editor: Roberts and colleagues (Feb. 5 issue)1 report that matching at the HLA-DR locus has significant effects on the survival of cadaveric renal grafts, whereas matching at the HLA-A and B loci has only small effects. They conclude that the allocation of kidneys from cadaveric donors should be based on HLA-DR matching, an approach that would also reduce the existing racial imbalance. This conclusion is in full accord with the findings of a single-center study reported by one of us and our colleagues in the Journal in 1980,2 findings that were subsequently confirmed in a larger series of patients treated with cyclosporine.3 In a Perspective article accompanying the study by Roberts et al., van Rood4 asks for longer follow-up studies. On the basis of our experience with 1336 patients who received a first cadaveric kidney between 1989 and 2002, all of whom were treated with cyclosporine, the estimated half-life of kidneys matched for the "broad" HLA-DR antigens 1 through 14 is approximately 14 years, as compared with approximately 8 years for HLA-DR–mismatched kidneys. Thus, we give highest priority to HLA-DR–matched combinations, and as a result, more than 50 percent of our patients now receive an HLA-DR–matched kidney. More sophisticated matching programs may result in further improvements. However, our matching scheme may be accomplished in single centers.
Erik Thorsby, M.D.
Per F. Pfeffer, M.D.
Rikshospitalet University Hospital
0027 Oslo, Norway
erik.thorsby@labmed.uio.no
References
Roberts JP, Wolfe RA, Bragg-Gresham L, et al. Effect of changing the priority for HLA matching on the rates and outcomes of kidney transplantation in minority groups. N Engl J Med 2004;350:545-551.
Moen T, Albrechtsen D, Flatmark A, et al. Importance of HLA-DR matching in cadaveric renal transplantation: a prospective one-center study of 170 transplants. N Engl J Med 1980;303:850-854.
Reis?ter AV, Leivestad T, Vartdal F, et al. A strong impact of matching for a limited number of HLA-DR antigens on graft survival and rejection episodes: a single-center study of first cadaveric kidneys to nonsensitized recipients. Transplantation 1998;66:523-528.
van Rood JJ. Weighing optimal graft survival through HLA matching against the equitable distribution of kidney allografts. N Engl J Med 2004;350:535-536.
To the Editor: We wish to point out that Roberts and colleagues' recommendation to eliminate HLA-B matching from consideration was implemented by the United Network for Organ Sharing more than six months ago. With regard to HLA matching, the current allocation system considers only the HLA-DR locus.1
Aaron Spital, M.D.
Kristin J. Wendt, M.P.H.
New York Organ Donor Network
New York, NY 10115
aspital@nyodn.org
References
United Network for Organ Sharing. Organ distribution: allocation of deceased kidneys. (Accessed April 22, 2004, at http://www.unos.org/policiesandbylaws/policies.asp?resources-true.)
To the Editor: Roberts et al. conclude that removing HLA-B matching as a priority for the allocation of cadaveric kidneys could increase the number of transplantations among nonwhites, with a justifiable increase in the rate of graft loss. They do not state how much increased priority, if any, should be given to HLA-DR matching. The current policy of giving 1 or 2 points for HLA-DR matching means that allocation is based primarily on waiting time. As stated, eliminating HLA-DR matching would increase the risk of rejection, graft loss, and death. Thus, knowing the effects of giving increased priority to HLA-DR matching would be of equal or even greater importance. Eliminating HLA-B matching as a priority would increase sensitization in transplant recipients, many of whom would probably require retransplantation — a situation that would be a disproportionate disadvantage to nonwhites.
Moreover, it must be recognized that many non-HLA factors underlie the racial imbalance among transplant recipients. We staunchly support equal access to transplantation but suggest that it should not require deliberately compromising (even to a small, but statistically significant, degree) the utility of such a scarce and valuable resource.
Malek Kamoun, M.D., Ph.D.
Marty T. Sellers, M.D.
University of Pennsylvania
Philadelphia, PA 19104
malekkam@mail.med.upenn.edu
The authors reply: We appreciate Thorsby and Pfeffer's confirmation of our findings concerning the outcomes of HLA-DR matching. We hope that the change in policy will result in similar results in the United States.
As Spital and Wendt point out, the policy we propose in our article has been implemented; it was put into effect by the Organ Procurement and Transplantation Network on May 7, 2003. It will be several years before a steady state is reached, and an evaluation of our predicted outcomes, as compared with actual outcomes, with respect to the racial distribution of organ transplantations can be performed. A preliminary evaluation of the policy suggests that after four months, a 7.7 percent increase in transplantations among nonwhites, which is similar to the change we predicted, has occurred.
Kamoun and Sellers question the sacrifice of the utility of the transplanted organ for an improved racial balance in kidney transplantation. The current objectives of the Organ Procurement and Transplantation Network for organ allocation "must strike a balance among competing, and often conflicting, objectives."1 These objectives include maximizing "patient and graft survival" and maximizing the "opportunity for patients with biological or medical disadvantages to receive a transplant." The argument for a strictly utilitarian system would represent a change in the current philosophy of organ allocation.
John P. Roberts, M.D.
University of California at San Francisco
San Francisco, CA 94143
robertsj@surgery.ucsf.edu
Robert A. Wolfe, Ph.D.
University of Michigan
Ann Arbor, MI 48103
Friedrich K. Port, M.D.
University Renal Research and Education Association
Ann Arbor, MI 48103
References
The Organ Procurement and Transplantation Network. Donation & transplantation: bioethics. (Accessed April 22, 2004, at http://www.optn.org/resources/bioethics.asp?index=8.)
Erik Thorsby, M.D.
Per F. Pfeffer, M.D.
Rikshospitalet University Hospital
0027 Oslo, Norway
erik.thorsby@labmed.uio.no
References
Roberts JP, Wolfe RA, Bragg-Gresham L, et al. Effect of changing the priority for HLA matching on the rates and outcomes of kidney transplantation in minority groups. N Engl J Med 2004;350:545-551.
Moen T, Albrechtsen D, Flatmark A, et al. Importance of HLA-DR matching in cadaveric renal transplantation: a prospective one-center study of 170 transplants. N Engl J Med 1980;303:850-854.
Reis?ter AV, Leivestad T, Vartdal F, et al. A strong impact of matching for a limited number of HLA-DR antigens on graft survival and rejection episodes: a single-center study of first cadaveric kidneys to nonsensitized recipients. Transplantation 1998;66:523-528.
van Rood JJ. Weighing optimal graft survival through HLA matching against the equitable distribution of kidney allografts. N Engl J Med 2004;350:535-536.
To the Editor: We wish to point out that Roberts and colleagues' recommendation to eliminate HLA-B matching from consideration was implemented by the United Network for Organ Sharing more than six months ago. With regard to HLA matching, the current allocation system considers only the HLA-DR locus.1
Aaron Spital, M.D.
Kristin J. Wendt, M.P.H.
New York Organ Donor Network
New York, NY 10115
aspital@nyodn.org
References
United Network for Organ Sharing. Organ distribution: allocation of deceased kidneys. (Accessed April 22, 2004, at http://www.unos.org/policiesandbylaws/policies.asp?resources-true.)
To the Editor: Roberts et al. conclude that removing HLA-B matching as a priority for the allocation of cadaveric kidneys could increase the number of transplantations among nonwhites, with a justifiable increase in the rate of graft loss. They do not state how much increased priority, if any, should be given to HLA-DR matching. The current policy of giving 1 or 2 points for HLA-DR matching means that allocation is based primarily on waiting time. As stated, eliminating HLA-DR matching would increase the risk of rejection, graft loss, and death. Thus, knowing the effects of giving increased priority to HLA-DR matching would be of equal or even greater importance. Eliminating HLA-B matching as a priority would increase sensitization in transplant recipients, many of whom would probably require retransplantation — a situation that would be a disproportionate disadvantage to nonwhites.
Moreover, it must be recognized that many non-HLA factors underlie the racial imbalance among transplant recipients. We staunchly support equal access to transplantation but suggest that it should not require deliberately compromising (even to a small, but statistically significant, degree) the utility of such a scarce and valuable resource.
Malek Kamoun, M.D., Ph.D.
Marty T. Sellers, M.D.
University of Pennsylvania
Philadelphia, PA 19104
malekkam@mail.med.upenn.edu
The authors reply: We appreciate Thorsby and Pfeffer's confirmation of our findings concerning the outcomes of HLA-DR matching. We hope that the change in policy will result in similar results in the United States.
As Spital and Wendt point out, the policy we propose in our article has been implemented; it was put into effect by the Organ Procurement and Transplantation Network on May 7, 2003. It will be several years before a steady state is reached, and an evaluation of our predicted outcomes, as compared with actual outcomes, with respect to the racial distribution of organ transplantations can be performed. A preliminary evaluation of the policy suggests that after four months, a 7.7 percent increase in transplantations among nonwhites, which is similar to the change we predicted, has occurred.
Kamoun and Sellers question the sacrifice of the utility of the transplanted organ for an improved racial balance in kidney transplantation. The current objectives of the Organ Procurement and Transplantation Network for organ allocation "must strike a balance among competing, and often conflicting, objectives."1 These objectives include maximizing "patient and graft survival" and maximizing the "opportunity for patients with biological or medical disadvantages to receive a transplant." The argument for a strictly utilitarian system would represent a change in the current philosophy of organ allocation.
John P. Roberts, M.D.
University of California at San Francisco
San Francisco, CA 94143
robertsj@surgery.ucsf.edu
Robert A. Wolfe, Ph.D.
University of Michigan
Ann Arbor, MI 48103
Friedrich K. Port, M.D.
University Renal Research and Education Association
Ann Arbor, MI 48103
References
The Organ Procurement and Transplantation Network. Donation & transplantation: bioethics. (Accessed April 22, 2004, at http://www.optn.org/resources/bioethics.asp?index=8.)