- Email: [email protected]
Ethical Considerations on Kidney Transplantation From Living Donors
Ethical Considerations on Kidney Transplantation From Living Donors P. Bruzzone, R. Pretagostini, L. Poli, M. Rossi, P.B. Berloco ABSTRACT Kidney transplantation from living donors is widely performed all over the world. Living nephrectomy for transplantation has no direct advantage for the donor other than increased self-esteem, but at least remains an extremely safe procedure, with a worldwide overall mortality rate of 0.03%. This theoretical risk to the donor seems to be justified by the socioeconomic advantages and increased quality of life of the recipient, especially in selected cases, such as pediatric patients, when living donor kidney transplantation can be performed in a preuremic phase, avoiding the psychological and physical stress of dialysis, which in children is not well tolerated and cannot prevent retarded growth. According to the Ethical Council of the Transplantation Society, commercialism must be prevented, not only for ethical but also medical reasons. The risks are too high not only for the donors, but also for the recipients, as a consequence of poor donor screening and evaluation with consequent transmission of human immunodeficiency virus or other infectious agents, as well as inappropriate medical and surgical management of donors and also of recipients, who are often discharged too early. Most public or private insurance companies are considering kidney donation a safe procedure without long-term impairment and, therefore, do not increase the premium, whereas recipient insurance of course should cover hospital fees for the donors. “Rewarded gifting” or other financial incentives to compensate for the inconvenience and loss of income related to the donation are not advisable, at least in our opinion. Our center does not perform anonymous living organ donation or “cross-over” transplantation.
K
IDNEY transplantation from living donors performed successfully for the first time in 1954 by Murray is now considered a good clinical solution complementary to cadaver (CD) kidney transplantation to increase the donor pool. With the increasing availability of dialysis, many centers subsequently discouraged transplantation from living donors, however, the introduction of Cyclosporine (CsA) with a significant improvement in the results of cadaver kidney transplantation together with a dramatic growth in the number of patients on the waiting list, due to an inadequate supply of cadaver kidneys, prompted expansion of the criteria for acceptable living donors. The validity of this procedure is based on many ethical and clinical considerations including the results that in most reports are better than with cadaver donor kidney transplantation, the free willingness of the donor, and the limited amount of risks for his or her health. Both conventional and laparoscopic living donor nephrectomy are safe procedures with a worldwide overall mortality of 0.03%.1 However, at least 4 kidney donors world world have developed end-stage renal
failure and have undergone kidney transplantation.2 Our center activated a living related donor (LRD) kidney transplantation program in 1967 and a living unrelated donor (LURD) kidney transplantation program in 1968, performing 62 kidney transplantation including LURDs. In the CsA era, our group did the first living donor kidney transplantation in 1982 and the first LURD transplantation Europe in 1983. MATERIALS AND METHODS The study population consisted of 398 LRD- among whom 35 pairs shared 2 haplotypes, 338 shared 1 haplotype (Group A), and 25 had no haplotypes in common. Of the 206 LURD (Group B), 171 were performed between spouse pairs (Group C) with 123 from wife to husband (Group C1) and 33 from husband to wife despite preFrom the Divisione Trapianti d’Organo, Dipartimento “Paride Stefanini,” Università di Roma “La Sapienza,” Rome, Italy. Address reprint requests to Paolo Bruzzone, MD, Via Santa Maria Goretti 38/10, 00199 Rome, Italy. E-mail: paolo.bruzzone@ fastwebnet.it
0041-1345/05/$–see front matter doi:10.1016/j.transproceed.2005.06.015
© 2005 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
2436
Transplantation Proceedings, 37, 2436 –2438 (2005)
ETHICAL CONSIDERATIONS transplantation pregnancies (Group C2) as well as 33 between relative in law or emotionally related patients (Group D). One hundred ninety-four pairs showed 3– 6 HLA-A, B, Dr mismatches (MM) with the donor and in 10 cases 0 –2 MM. Donor and recipient mean ages were 48 ⫾ 87 and 34.8 ⫾ 8.2 in Group A and 46 ⫾ 11.2 and 47 ⫾ 11.2 in Group B, respectively. The posttransplantation immunosuppressive therapy was based on CsA. A 2 test was used to assess statistical significance.
RESULTS
The donor mortality rate was 0%; the perioperative morbidity rate was 15.2%. Grafts functioned immediately after surgery. The actuarial 1-, 5-, 10-, and 15-year graft survivals rates were 92%, 87%, 78%, and 64% for Group A versus 89%, 78%, 71%, and 70% (Group B). (P), Group C1 90%, 75%, 67%, and 69% versus Group C2, 81%, 74%, 72%, 62% (NS), respectively. Also, the differences between Group C 88%, 78%, 66%, and 60% and Group D 91%, 80%, 71%, and 61% were not significant. DISCUSSION
There was no statistically significant difference between LURD and LRD in graft survival. Immunological factors, such as HLA compatibility, pretransplantation blood transfusions, and previous pregnancies, seem to not influence graft survival. According to various authors, the morbidity rates ranges from 10%–20%. Major complications, include such as severe hemorrhage, pulmonary embolism, and pneumothorax, can be prevented by accurate surgical technique and prompt donor mobilization after surgery. According to published data3 as well as to our personal experience,4 – 6 presently there could be no clinical but only ethical objections to LURD kidney transplantation. Many donors report increased self-esteem as a consequence of having helped to restore the health and improve the quality of life of a significant loved one. Some people in fact could argue that the theoretical risk to the donor, which as previously discussed is extremely low, does not compensate for the evident socioeconomic advantages and increased quality of life of the recipient, who avoids a long time on the waiting list and is usually able to return to social activity and work earlier. In selected cases, such as younger recipients, kidney transplantation can be performed in a preuremic phase, avoiding psychological and physical stress of dialysis, which in pediatric cases is not well tolerated and cannot prevent retarded growth. The consent has to be free and without any form of coercion, which could be subtle and difficult to detect, because some forms of psychological conditioning are difficult to recognize in a family setting, whereas economic dealings may be concealed on purpose even by the donor. According to the Consensus Statement of the Amsterdam Forum on the Care of the Live Kidney Donor, organized on April 1– 4 2004 by the Ethics Committee of the Transplantation Society, “Minors less than 18 years of age should not be used as living kidney donors.”7 In agreement with the guidelines suggested by the Ethical Council of the Trans-
2437
plantation Society, commercialism must be effectively prevented, possibly by only using as living unrelated donors spouses or relatives-in-law with a great interest in the recipient’s health condition. One must acknowledge that the results of truly commercial kidney transplantations are discouraging, providing a further argument against transplantation from paid donors, in addition to the consequences of poor donor screening with consequent transmission of human immunodeficiency virus and other infectious agents, and inappropriate medical and surgical management of recipients, who present an unacceptable morbidity rate, and, often after having been discharged too early, seek medical attention in their native countries. “Rewarded gifting” or other financial incentives to compensate for the inconvenience and loss of income related to the donation are not advisable, at least in our opinion. All over the world most public or private insurance companies consider living kidney donation to be a safe procedure without long-term harm or impairment and, therefore, do not increase the premium for these donors, whereas the recipients’ insurance companies of course cover the donors hospital fees. Due to obvious ethical reasons, transplantation physicians and surgeons cannot take part in kidney donation from prisoners, even where such a procedure has been proposed to death-row inmates as an alternative to execution. To increase the possibility of LURD kidney transplantation between blood group–incompatible pairs, in 1986 Rapaport proposed a national network to exchange kidneys harvested from living donors with blood groups not compatible with their emotionally related recipients. This suggestion was proposed again in 1997 by Ross as a local program, by Park et al,8 and by other authors. This so-called cross-over procedure could allow one to perform living kidney transplantation also in cases of couples with a direct positive cross-match and, where applied on a larger scale, could also allow HLA matching, which may be useful in this kind of transplantation. In our experience, only 5% of couples would benefit from a cross-over, which could theoretically have negative psychological and ethical effects, such as a decreased willingness to donate to a stranger or a higher risk of donor coercion and organ commercialism. Therefore, our center does not perform “cross-over” transplantation. In conclusion, we certainly agree with the guidelines issued by the International Congress on Ethics in Organ Transplantation (Munich, December 10 –13, 2002)— kidney transplantation from living donors is a safe, effective procedure that should not be discouraged. REFERENCES 1. Ciszek M, Paczek L, Rowinski W: Clinical outcome of living kidney donation. Transplant Proc 35:1179, 2003 2. Gracida C, Espinoza R, Cancino J: Can a living kidney donor become a kidney recipient? Transplant Proc 36:1630, 2004 3. D’Alessandro AM, Pirsch JD, Knechtle SJ, et al: Living unrelated renal donation: the University of Wisconsin experience. Surgery 124:604, 1998
2438 4. Berloco, P, Alfani D, Bruzzone P, et al: Is unrelated living donor a valid organ source in renal transplantation under CyA therapy? Transplant Proc 23:912, 1991 5. Alfani D, Pretagostini, R, Bruzzone P, et al: Kidney transplantation from living unrelated donors. In Cecka M, Terasaki PI (eds): Clinical Transplants 1998. Los Angeles, Calif; UCLA Tissue Typing Laboratory; 1999, P 205
BRUZZONE, PRETAGOSTINI, POLI ET AL 6. Cortesini R, Pretagostini, R, Bruzzone P, et al: Living unrelated kidney transplantation. World J Surg 26:238, 2002 7. The Ethics Committee of the Transplantation Society: The Consensus Statement of the Amsterdam Forum on the Care of the Live Kidney Donor. Transplantation 78:491, 2004 8. Park L, Moon JI, Kim SI, et al: Exchange donor program in kidney transplantation. Transplantation 67:336, 1999
K
IDNEY transplantation from living donors performed successfully for the first time in 1954 by Murray is now considered a good clinical solution complementary to cadaver (CD) kidney transplantation to increase the donor pool. With the increasing availability of dialysis, many centers subsequently discouraged transplantation from living donors, however, the introduction of Cyclosporine (CsA) with a significant improvement in the results of cadaver kidney transplantation together with a dramatic growth in the number of patients on the waiting list, due to an inadequate supply of cadaver kidneys, prompted expansion of the criteria for acceptable living donors. The validity of this procedure is based on many ethical and clinical considerations including the results that in most reports are better than with cadaver donor kidney transplantation, the free willingness of the donor, and the limited amount of risks for his or her health. Both conventional and laparoscopic living donor nephrectomy are safe procedures with a worldwide overall mortality of 0.03%.1 However, at least 4 kidney donors world world have developed end-stage renal
failure and have undergone kidney transplantation.2 Our center activated a living related donor (LRD) kidney transplantation program in 1967 and a living unrelated donor (LURD) kidney transplantation program in 1968, performing 62 kidney transplantation including LURDs. In the CsA era, our group did the first living donor kidney transplantation in 1982 and the first LURD transplantation Europe in 1983. MATERIALS AND METHODS The study population consisted of 398 LRD- among whom 35 pairs shared 2 haplotypes, 338 shared 1 haplotype (Group A), and 25 had no haplotypes in common. Of the 206 LURD (Group B), 171 were performed between spouse pairs (Group C) with 123 from wife to husband (Group C1) and 33 from husband to wife despite preFrom the Divisione Trapianti d’Organo, Dipartimento “Paride Stefanini,” Università di Roma “La Sapienza,” Rome, Italy. Address reprint requests to Paolo Bruzzone, MD, Via Santa Maria Goretti 38/10, 00199 Rome, Italy. E-mail: paolo.bruzzone@ fastwebnet.it
0041-1345/05/$–see front matter doi:10.1016/j.transproceed.2005.06.015
© 2005 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
2436
Transplantation Proceedings, 37, 2436 –2438 (2005)
ETHICAL CONSIDERATIONS transplantation pregnancies (Group C2) as well as 33 between relative in law or emotionally related patients (Group D). One hundred ninety-four pairs showed 3– 6 HLA-A, B, Dr mismatches (MM) with the donor and in 10 cases 0 –2 MM. Donor and recipient mean ages were 48 ⫾ 87 and 34.8 ⫾ 8.2 in Group A and 46 ⫾ 11.2 and 47 ⫾ 11.2 in Group B, respectively. The posttransplantation immunosuppressive therapy was based on CsA. A 2 test was used to assess statistical significance.
RESULTS
The donor mortality rate was 0%; the perioperative morbidity rate was 15.2%. Grafts functioned immediately after surgery. The actuarial 1-, 5-, 10-, and 15-year graft survivals rates were 92%, 87%, 78%, and 64% for Group A versus 89%, 78%, 71%, and 70% (Group B). (P), Group C1 90%, 75%, 67%, and 69% versus Group C2, 81%, 74%, 72%, 62% (NS), respectively. Also, the differences between Group C 88%, 78%, 66%, and 60% and Group D 91%, 80%, 71%, and 61% were not significant. DISCUSSION
There was no statistically significant difference between LURD and LRD in graft survival. Immunological factors, such as HLA compatibility, pretransplantation blood transfusions, and previous pregnancies, seem to not influence graft survival. According to various authors, the morbidity rates ranges from 10%–20%. Major complications, include such as severe hemorrhage, pulmonary embolism, and pneumothorax, can be prevented by accurate surgical technique and prompt donor mobilization after surgery. According to published data3 as well as to our personal experience,4 – 6 presently there could be no clinical but only ethical objections to LURD kidney transplantation. Many donors report increased self-esteem as a consequence of having helped to restore the health and improve the quality of life of a significant loved one. Some people in fact could argue that the theoretical risk to the donor, which as previously discussed is extremely low, does not compensate for the evident socioeconomic advantages and increased quality of life of the recipient, who avoids a long time on the waiting list and is usually able to return to social activity and work earlier. In selected cases, such as younger recipients, kidney transplantation can be performed in a preuremic phase, avoiding psychological and physical stress of dialysis, which in pediatric cases is not well tolerated and cannot prevent retarded growth. The consent has to be free and without any form of coercion, which could be subtle and difficult to detect, because some forms of psychological conditioning are difficult to recognize in a family setting, whereas economic dealings may be concealed on purpose even by the donor. According to the Consensus Statement of the Amsterdam Forum on the Care of the Live Kidney Donor, organized on April 1– 4 2004 by the Ethics Committee of the Transplantation Society, “Minors less than 18 years of age should not be used as living kidney donors.”7 In agreement with the guidelines suggested by the Ethical Council of the Trans-
2437
plantation Society, commercialism must be effectively prevented, possibly by only using as living unrelated donors spouses or relatives-in-law with a great interest in the recipient’s health condition. One must acknowledge that the results of truly commercial kidney transplantations are discouraging, providing a further argument against transplantation from paid donors, in addition to the consequences of poor donor screening with consequent transmission of human immunodeficiency virus and other infectious agents, and inappropriate medical and surgical management of recipients, who present an unacceptable morbidity rate, and, often after having been discharged too early, seek medical attention in their native countries. “Rewarded gifting” or other financial incentives to compensate for the inconvenience and loss of income related to the donation are not advisable, at least in our opinion. All over the world most public or private insurance companies consider living kidney donation to be a safe procedure without long-term harm or impairment and, therefore, do not increase the premium for these donors, whereas the recipients’ insurance companies of course cover the donors hospital fees. Due to obvious ethical reasons, transplantation physicians and surgeons cannot take part in kidney donation from prisoners, even where such a procedure has been proposed to death-row inmates as an alternative to execution. To increase the possibility of LURD kidney transplantation between blood group–incompatible pairs, in 1986 Rapaport proposed a national network to exchange kidneys harvested from living donors with blood groups not compatible with their emotionally related recipients. This suggestion was proposed again in 1997 by Ross as a local program, by Park et al,8 and by other authors. This so-called cross-over procedure could allow one to perform living kidney transplantation also in cases of couples with a direct positive cross-match and, where applied on a larger scale, could also allow HLA matching, which may be useful in this kind of transplantation. In our experience, only 5% of couples would benefit from a cross-over, which could theoretically have negative psychological and ethical effects, such as a decreased willingness to donate to a stranger or a higher risk of donor coercion and organ commercialism. Therefore, our center does not perform “cross-over” transplantation. In conclusion, we certainly agree with the guidelines issued by the International Congress on Ethics in Organ Transplantation (Munich, December 10 –13, 2002)— kidney transplantation from living donors is a safe, effective procedure that should not be discouraged. REFERENCES 1. Ciszek M, Paczek L, Rowinski W: Clinical outcome of living kidney donation. Transplant Proc 35:1179, 2003 2. Gracida C, Espinoza R, Cancino J: Can a living kidney donor become a kidney recipient? Transplant Proc 36:1630, 2004 3. D’Alessandro AM, Pirsch JD, Knechtle SJ, et al: Living unrelated renal donation: the University of Wisconsin experience. Surgery 124:604, 1998
2438 4. Berloco, P, Alfani D, Bruzzone P, et al: Is unrelated living donor a valid organ source in renal transplantation under CyA therapy? Transplant Proc 23:912, 1991 5. Alfani D, Pretagostini, R, Bruzzone P, et al: Kidney transplantation from living unrelated donors. In Cecka M, Terasaki PI (eds): Clinical Transplants 1998. Los Angeles, Calif; UCLA Tissue Typing Laboratory; 1999, P 205
BRUZZONE, PRETAGOSTINI, POLI ET AL 6. Cortesini R, Pretagostini, R, Bruzzone P, et al: Living unrelated kidney transplantation. World J Surg 26:238, 2002 7. The Ethics Committee of the Transplantation Society: The Consensus Statement of the Amsterdam Forum on the Care of the Live Kidney Donor. Transplantation 78:491, 2004 8. Park L, Moon JI, Kim SI, et al: Exchange donor program in kidney transplantation. Transplantation 67:336, 1999