- Email: [email protected]
Living Donor Kidney Exchange for Both ABO-Incompatible and Crossmatch Positive Donor–Recipient Combinations
DONATION
Living Donor Kidney Exchange for Both ABO-Incompatible and Crossmatch Positive Donor–Recipient Combinations M. de Klerk, B.J.J.M. Haase-Kromwijk, F.H.J. Claas, M. Witvliet, and W. Weimar ABSTRACT Background. Strategies to decrease the wait time for kidney transplantation include the use of living donor kidneys. However, it is not always possible to donate directly, due to ABO blood type incompatibility or a positive crossmatch. Therefore, other options were explored, including a program for living donor kidney exchange. Methods. All Dutch kidney transplantation centers agreed on a common donor kidney exchange protocol. The Dutch Transplantation Foundation is responsible for the allocation, crossmatches are centrally performed, and exchanges take place on an anonymous basis. Donors travel to the recipient centers. Surgical procedures are simultaneously scheduled. Results. From January 2004, we registered in total 116 combinations consisting of blood type–incompatible pairs (n ⫽ 62) and positive crossmatch pairs (n ⫽ 54). In eight match procedures we created 58 new donor–recipient combinations with negative crossmatches, including six triplets and 20 doublets. It proved to be significantly (P ⫽ .0014) less difficult to find a solution for the crossmatch-positive combinations than for the blood type– incompatible combinations (67% vs 35%). Conclusion. The Dutch national living donor kidney exchange program resulted in a 50% success rate. Combining blood type–incompatible and crossmatch-positive donor– recipient pairs in one program is a realistic option for all blood type combinations.
A
MAJOR PROBLEM for most transplant programs is the ever-increasing wait time for deceased donor organs. The annual number of deceased donor kidney
transplantations in The Netherlands has not changed much in the last 2 decades but stabilized at 350 to 400 from 1982 until now. In the same period the number of Dutch patients
From the Department of Internal Medicine–Transplantation (M.D.K., W.W.), Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands; Dutch Transplantation Foundation (M.D.K., B.J.J.M.H.-K., W.W.), Leiden, The Netherlands; and National Reference Laboratory for Histocompatibility, Department of Immunohematology and Blood Transfusion
(F.H.J.C., M.W.), Leiden University Medical Centre, Leiden, The Netherlands. Address reprint requests to Marry de Klerk, Erasmus Medical Centre Rotterdam, Department of Internal Medicine–Transplantation, Office D 408, PO Box 2040, 3000 CA Rotterdam. The Netherlands. E-mail: [email protected]
© 2006 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/06/$–see front matter doi:10.1016/j.transproceed.2006.08.157
Transplantation Proceedings, 38, 2793–2795 (2006)
2793
2794
on the waiting list increased from 400 to 1100. Accordingly, the wait time for a postmortal kidney transplant steadily increased from approximately 1 year in 1982 to 4 years in 2006.1 Therefore living donor kidney transplantation became more and more acceptable for patients and health professionals. Living donation in The Netherlands had a slow start in the 1980s, increased in the 1990s, and accelerated in the last 5 years. The year 2003 was the first year in which more living than deceased donors were registered. In 2005 the number of living kidney transplantations rose to 40% of the total number performed, while there were 211 deceased and 274 living donors. At the start of the living donation program, only genetically related persons could opt for donation. Later, also genetically unrelated individuals, such as spouses, partners, or good friends, were accepted. In the meanwhile, it has been recognized that unrelated living donor transplants have results equivalent to related living donor transplants.2 Unfortunately, willing donors cannot always donate directly to their intended recipients due to a positive crossmatch or an ABO blood type incompatibility. In these cases, exchanging donors could be a solution. Such an exchange is possible between two pairs, but this restriction will limit the success rate of the program. More possibilities can be created when exchanges between three pairs are considered: so called triplets. Theoretically quartets, quintets, sextets, and so on will help even more patients, but these solutions are logistically difficult to realize on a routine basis. For that reason we have limited our program to triple exchanges. In the present report we describe the 2-year results of a multicenter donor kidney exchange program in The Netherlands. METHODS AND PATIENTS In The Netherlands, a national program is operating in which all seven kidney transplant centers cooperate under the supervision of the Dutch Transplantation Foundation. Data of incompatible donor–recipient pairs including age, blood type, and HLA antigens from donor and recipient, unacceptable HLA antigens for the recipient, and wait time, calculated from the first day of renal replacement therapy, are sent to the Dutch Transplantation Foundation. A computerized match program runs every 3 months. Usually, donor–recipient pairs can be matched with multiple other pairs. Therefore, a number of priorizing criteria are necessary. Allocation is based on blood type, first identical than compatible, match-probability, wait time, and donor age. The basic principle of the match probability is to ensure that highly sensitized recipients will indeed receive a kidney when there is a suitable donor in the crossover pool. The recipient with the smallest chance of finding a compatible donor in the pool will be ranked first.3 Crossmatches are performed in the central HLA-reference laboratory in Leiden. All centers have agreed that the donor will travel to the recipient’s center for a final acceptance. Both surgical procedures start at the same time and in the recipient’s centers. There is a strict anonymity between both donor–recipient pairs.4 After the procedures, donor and recipient follow-up will be in the recipient’s centers.
Patients In the last 2 years, between January 2004 and December 2005, 116 donor–recipient pairs participated. There were 62 couples with
DE
KLERK, HAASE-KROMWIJK, CLAAS ET AL
an incompatible blood type and 54 with a positive crossmatch. The input by the seven centers was comparable except for one center: Leiden 25, Rotterdam 25, Nijmegen 20, Amsterdam 19, Groningen 12, Utrecht 12, and Maastricht 3. Sixty percent of the potential donors were partners (n ⫽ 70). The other subgroups consisted of parents (two fathers and 11 mothers), siblings (five brothers and four sisters), childrens (four sons and two daughters), five other family members, and 13 nonrelatives. In most groups there was no gender difference although there were far more mothers than fathers as potential donors. Median age of the donor was 52 years with a range of 26 to 78 years. The characteristics of the 116 recipients were: median age recipients, 51 (range 17 to 73) years: median wait-time, 1 year and 4 months, with a range up to 14.5 years. Median panel-reactive antibodies (PRA) of the 62 recipients in the blood type–incompatible group was 2% (range 0% to 100%) and in the positive crossmatch group (n ⫽ 54), 41% (range 0% to 100%).
RESULTS
On the basis of blood type and HLA acceptables we were able to make 518 combinations for in total 91 pairs. For 25 pairs we found no possibilities at all. In the latter group the blood type–incompatible pairs significantly (P ⫽ .0006) dominated (21 out of the 25). Thereafter, we made a further selection on the basis of match probability for the 91 pairs with match possibilities. This resulted in 58 combinations that proved to have negative crossmatches: 22 blood type–incompatible and 36 positive crossmatch pairs (six triplets and 20 doublets). This second selection was not associated with a significant difference in dropout rate between the two patient groups, indicating the fairness of the allocation procedure by match probability. Part of the success of this program depends on the creation of new couples out of blood type–incompatible and crossmatch-positive pairs. Indeed 22 times such a combination was made. The success rate in the positive crossmatch group was 67%, while in the blood type–incompatible group we achieved a smaller success rate of 35%. For the blood type–incompatible pairs with a blood type O recipients, it was even more difficult to find a matching couple, but it was still possible in 8 out of the 42 cases (19%). Median PRA of the 22 matched recipients in the blood type–incompatible group was 1% (range 0% to 27%) and in 36 patients in the matched positive crossmatch group, 34% (range 0% to 100%). DISCUSSION
We show that a living donor exchange program offers enough opportunities even when relatively small groups of patients are considered. So this is likely the driving force for regional cooperation. More pairs will be served by a combined approach enrolling ABO blood type–incompatible and positive crossmatch pairs into one program. In this case even donor–recipient pairs with blood type O recipients can profit as we showed for 19% of the candidates. At the same time immunized patients can find a suitable donor too. We were able to find match possibilities for 62% immunized recipients (34 out of 55) and 20% high immunized recipients (2 out of 10). We encourage all living donor
LIVING DONOR KIDNEY EXCHANGE
kidney transplant centers to explore the feasibility of introducing our exchange program in their routine transplantation care.
REFERENCES 1. Dutch Transplantation Foundation data as of February 20, obtained from and available at the Dutch Transplantation Foundation website, htpp//www.transplantatiestichting.nl, 2006
2795 2. Terasaki PI, Cecka JM, Gjertson DW, et al: High survival rates of kidney transplants from spousal and living unrelated donors. N Engl J Med 333:333, 1995 3. Keizer KM, de Klerk M, Haasse-Kromwijk BJJM, Weimar W: The Dutch algorithm for the allocation in living donor kidney exchange. Transplant Proc 37:589, 2005 4. de Klerk M, Luchtenburg AE, Zuidema WC, et al: Acceptability and feasibility of cross-over kidney transplantation. In Gutmann T, Daar AS, Sells RA, et al (Eds): Ethical, Legal, and Social Issues in Organ Transplantation. Lengerich: PABST Science Publishers; 2004, p 255
Living Donor Kidney Exchange for Both ABO-Incompatible and Crossmatch Positive Donor–Recipient Combinations M. de Klerk, B.J.J.M. Haase-Kromwijk, F.H.J. Claas, M. Witvliet, and W. Weimar ABSTRACT Background. Strategies to decrease the wait time for kidney transplantation include the use of living donor kidneys. However, it is not always possible to donate directly, due to ABO blood type incompatibility or a positive crossmatch. Therefore, other options were explored, including a program for living donor kidney exchange. Methods. All Dutch kidney transplantation centers agreed on a common donor kidney exchange protocol. The Dutch Transplantation Foundation is responsible for the allocation, crossmatches are centrally performed, and exchanges take place on an anonymous basis. Donors travel to the recipient centers. Surgical procedures are simultaneously scheduled. Results. From January 2004, we registered in total 116 combinations consisting of blood type–incompatible pairs (n ⫽ 62) and positive crossmatch pairs (n ⫽ 54). In eight match procedures we created 58 new donor–recipient combinations with negative crossmatches, including six triplets and 20 doublets. It proved to be significantly (P ⫽ .0014) less difficult to find a solution for the crossmatch-positive combinations than for the blood type– incompatible combinations (67% vs 35%). Conclusion. The Dutch national living donor kidney exchange program resulted in a 50% success rate. Combining blood type–incompatible and crossmatch-positive donor– recipient pairs in one program is a realistic option for all blood type combinations.
A
MAJOR PROBLEM for most transplant programs is the ever-increasing wait time for deceased donor organs. The annual number of deceased donor kidney
transplantations in The Netherlands has not changed much in the last 2 decades but stabilized at 350 to 400 from 1982 until now. In the same period the number of Dutch patients
From the Department of Internal Medicine–Transplantation (M.D.K., W.W.), Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands; Dutch Transplantation Foundation (M.D.K., B.J.J.M.H.-K., W.W.), Leiden, The Netherlands; and National Reference Laboratory for Histocompatibility, Department of Immunohematology and Blood Transfusion
(F.H.J.C., M.W.), Leiden University Medical Centre, Leiden, The Netherlands. Address reprint requests to Marry de Klerk, Erasmus Medical Centre Rotterdam, Department of Internal Medicine–Transplantation, Office D 408, PO Box 2040, 3000 CA Rotterdam. The Netherlands. E-mail: [email protected]
© 2006 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/06/$–see front matter doi:10.1016/j.transproceed.2006.08.157
Transplantation Proceedings, 38, 2793–2795 (2006)
2793
2794
on the waiting list increased from 400 to 1100. Accordingly, the wait time for a postmortal kidney transplant steadily increased from approximately 1 year in 1982 to 4 years in 2006.1 Therefore living donor kidney transplantation became more and more acceptable for patients and health professionals. Living donation in The Netherlands had a slow start in the 1980s, increased in the 1990s, and accelerated in the last 5 years. The year 2003 was the first year in which more living than deceased donors were registered. In 2005 the number of living kidney transplantations rose to 40% of the total number performed, while there were 211 deceased and 274 living donors. At the start of the living donation program, only genetically related persons could opt for donation. Later, also genetically unrelated individuals, such as spouses, partners, or good friends, were accepted. In the meanwhile, it has been recognized that unrelated living donor transplants have results equivalent to related living donor transplants.2 Unfortunately, willing donors cannot always donate directly to their intended recipients due to a positive crossmatch or an ABO blood type incompatibility. In these cases, exchanging donors could be a solution. Such an exchange is possible between two pairs, but this restriction will limit the success rate of the program. More possibilities can be created when exchanges between three pairs are considered: so called triplets. Theoretically quartets, quintets, sextets, and so on will help even more patients, but these solutions are logistically difficult to realize on a routine basis. For that reason we have limited our program to triple exchanges. In the present report we describe the 2-year results of a multicenter donor kidney exchange program in The Netherlands. METHODS AND PATIENTS In The Netherlands, a national program is operating in which all seven kidney transplant centers cooperate under the supervision of the Dutch Transplantation Foundation. Data of incompatible donor–recipient pairs including age, blood type, and HLA antigens from donor and recipient, unacceptable HLA antigens for the recipient, and wait time, calculated from the first day of renal replacement therapy, are sent to the Dutch Transplantation Foundation. A computerized match program runs every 3 months. Usually, donor–recipient pairs can be matched with multiple other pairs. Therefore, a number of priorizing criteria are necessary. Allocation is based on blood type, first identical than compatible, match-probability, wait time, and donor age. The basic principle of the match probability is to ensure that highly sensitized recipients will indeed receive a kidney when there is a suitable donor in the crossover pool. The recipient with the smallest chance of finding a compatible donor in the pool will be ranked first.3 Crossmatches are performed in the central HLA-reference laboratory in Leiden. All centers have agreed that the donor will travel to the recipient’s center for a final acceptance. Both surgical procedures start at the same time and in the recipient’s centers. There is a strict anonymity between both donor–recipient pairs.4 After the procedures, donor and recipient follow-up will be in the recipient’s centers.
Patients In the last 2 years, between January 2004 and December 2005, 116 donor–recipient pairs participated. There were 62 couples with
DE
KLERK, HAASE-KROMWIJK, CLAAS ET AL
an incompatible blood type and 54 with a positive crossmatch. The input by the seven centers was comparable except for one center: Leiden 25, Rotterdam 25, Nijmegen 20, Amsterdam 19, Groningen 12, Utrecht 12, and Maastricht 3. Sixty percent of the potential donors were partners (n ⫽ 70). The other subgroups consisted of parents (two fathers and 11 mothers), siblings (five brothers and four sisters), childrens (four sons and two daughters), five other family members, and 13 nonrelatives. In most groups there was no gender difference although there were far more mothers than fathers as potential donors. Median age of the donor was 52 years with a range of 26 to 78 years. The characteristics of the 116 recipients were: median age recipients, 51 (range 17 to 73) years: median wait-time, 1 year and 4 months, with a range up to 14.5 years. Median panel-reactive antibodies (PRA) of the 62 recipients in the blood type–incompatible group was 2% (range 0% to 100%) and in the positive crossmatch group (n ⫽ 54), 41% (range 0% to 100%).
RESULTS
On the basis of blood type and HLA acceptables we were able to make 518 combinations for in total 91 pairs. For 25 pairs we found no possibilities at all. In the latter group the blood type–incompatible pairs significantly (P ⫽ .0006) dominated (21 out of the 25). Thereafter, we made a further selection on the basis of match probability for the 91 pairs with match possibilities. This resulted in 58 combinations that proved to have negative crossmatches: 22 blood type–incompatible and 36 positive crossmatch pairs (six triplets and 20 doublets). This second selection was not associated with a significant difference in dropout rate between the two patient groups, indicating the fairness of the allocation procedure by match probability. Part of the success of this program depends on the creation of new couples out of blood type–incompatible and crossmatch-positive pairs. Indeed 22 times such a combination was made. The success rate in the positive crossmatch group was 67%, while in the blood type–incompatible group we achieved a smaller success rate of 35%. For the blood type–incompatible pairs with a blood type O recipients, it was even more difficult to find a matching couple, but it was still possible in 8 out of the 42 cases (19%). Median PRA of the 22 matched recipients in the blood type–incompatible group was 1% (range 0% to 27%) and in 36 patients in the matched positive crossmatch group, 34% (range 0% to 100%). DISCUSSION
We show that a living donor exchange program offers enough opportunities even when relatively small groups of patients are considered. So this is likely the driving force for regional cooperation. More pairs will be served by a combined approach enrolling ABO blood type–incompatible and positive crossmatch pairs into one program. In this case even donor–recipient pairs with blood type O recipients can profit as we showed for 19% of the candidates. At the same time immunized patients can find a suitable donor too. We were able to find match possibilities for 62% immunized recipients (34 out of 55) and 20% high immunized recipients (2 out of 10). We encourage all living donor
LIVING DONOR KIDNEY EXCHANGE
kidney transplant centers to explore the feasibility of introducing our exchange program in their routine transplantation care.
REFERENCES 1. Dutch Transplantation Foundation data as of February 20, obtained from and available at the Dutch Transplantation Foundation website, htpp//www.transplantatiestichting.nl, 2006
2795 2. Terasaki PI, Cecka JM, Gjertson DW, et al: High survival rates of kidney transplants from spousal and living unrelated donors. N Engl J Med 333:333, 1995 3. Keizer KM, de Klerk M, Haasse-Kromwijk BJJM, Weimar W: The Dutch algorithm for the allocation in living donor kidney exchange. Transplant Proc 37:589, 2005 4. de Klerk M, Luchtenburg AE, Zuidema WC, et al: Acceptability and feasibility of cross-over kidney transplantation. In Gutmann T, Daar AS, Sells RA, et al (Eds): Ethical, Legal, and Social Issues in Organ Transplantation. Lengerich: PABST Science Publishers; 2004, p 255