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Living Donor Kidney Transplants: Personal Reflections
Living Donor Kidney Transplants: Personal Reflections John S. Najarian ABSTRACT Short- and long-term living kidney donor morbidity and mortality are discussed herein. The analysis includes over 3000 living donor kidney transplants from 1963 through 2002 at a single institution. The category of living donors includes living related donors, such as fathers, mothers, siblings, offspring, and other genetically related donors, as well as living unrelated donors, such as spouses, friends, or altruistic strangers. Graft and patient survival rates with living related and unrelated living donors are compared to rates with cadaveric donors. Donor risks are discussed, including short-term surgical risks as well as long-term risks of impaired renal function, possible hypertension, and psychological risks. Finally, early and late donor mortality statistics are presented. In addition, the benefits to potential donors are reviewed. Donors are carefully screened before donation. During this screening process, a significant number of donors have been found to have abnormal renal function—some had undisclosed hypertension and others had unknown cardiovascular disease. In addition, six malignancies were found, eventually resulting in curative resection. A secondary benefit to donors was reported in a study from Norway and Sweden, which showed that donors had improved long-term survival versus the general population. Our own long-term studies involving follow-up of 20 to 30 years after kidney donation have shown no significant difference in donor renal function, blood pressure, and incidence of proteinuria, as compared with their nondonor siblings. We also found donors to be perfectly normal in all other categories; several had even undergone normal pregnancies after donation. Most donors reported a high quality of life, with a boost in self-esteem and an increased sense of well-being: 96% felt it was a positive experience. In conclusion, living kidney donation has a very low mortality rate. Long-term follow-up shows minimal impact after donation. Donor quality of life is reported as excellent.
M
Y INTEREST in and advocacy for living donor kidney transplants began in 1963 when I performed my first clinical kidney transplant in San Francisco. It was obvious from the first identical twin transplant (Boston, 1954)1 that living donor transplants were likely to be more convenient and successful than deceased donor transplants. This continued to be true even for nonidentical twin transplants, with Imuran and prednisone as the only immunosuppressive agents. From the outset, immediate and late results were more favorable with living related donor transplants. Moreover, the use of organs from deceased donors initially presented a difficult logistical challenge. For the most part, deceased donor transplants in the early days required that the recipient be in the university hospital awaiting the possible
availability of an organ, which usually came from a separate hospital or trauma unit and had to be transported. This logistical challenge fueled our enthusiasm for attempting to persuade recipients to find living related donors whenever possible. In 1966, after Dr. Folkert Belzer had completed his residency at the University of Oregon and was appointed a junior staff surgeon at the University of California-San Francisco (UCSF), I was asked by our chairman, Dr. Bert Dunphy, to find a suitable research project for Dr. Belzer. His primary interest was in vascular surgery; he had virtually no training in immunology. I suggested that his project From the Department of Surgery, Fairview-University Medical Center, Minneapolis, Minnesota.
0041-1345/05/$–see front matter doi:10.1016/j.transproceed.2005.10.079
© 2005 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
3592
Transplantation Proceedings, 37, 3592–3594 (2005)
LIVING DONOR KIDNEY TRANSPLANTS
in our transplantation laboratory could be to explore the possibilities of developing a technique for preserving kidneys from deceased donors. Short-term preservation would allow prospective recipients to remain at home until a deceased donor kidney became available. Furthermore, adequate time would be provided pretransplant for appropriate tissue typing of the donor kidney. Dr. Belzer pursued this investigation in our laboratory. By serendipity, he eventually came up with a solution that would allow short-term preservation of a kidney for transplantation. One afternoon, after he had bled a series of dogs to obtain plasma for his kidney perfusion experiments, he was unable to use the plasma immediately and instead placed it in a refrigerator overnight. The next morning, he found that a layer of flocculation had formed in the plasma, which turned out to consist of lipids. He then filtered the plasma to remove the flocculent layer, so that the resultant clear plasma could be used for kidney perfusion. This “cryoprecipitated” plasma readily perfused the kidney without obstruction. In the past, perfusion of freshly drawn, unaltered plasma through the kidney had invariably resulted in vascular obstruction in the cold kidneys. Subsequently, he developed a pumping mechanism, thereby establishing perfusion preservation. This research (done in 1966) was published in the Lancet in 1967.2 Shortly thereafter, Dr. Jeffrey Collins3 of the University of California-Los Angeles (UCLA) developed a perfusion solution now known as Collins Solution that could be used to preserve kidneys for 12 hours at 0°C; eventually, it permitted cold storage of kidneys for up to 2 days. With kidneys that could be stored for 12 or more hours, simple transportation from one institution to another was now possible. Thanks to the Belzer technique and the Collins Solution, the logistical difficulties of deceased donor kidney transplantation were primarily overcome. However, living related kidneys, when available, remained our first choice. On arriving at the University of Minnesota in 1967, I was pleasantly surprised to find that strong family ties in that state meant that a number of family members would frequently come forward as a possible kidney donor for a loved one in renal failure. In the Minnesota transplant program, living donation quickly increased to represent over 65% of our donors. It has remained at well over 50% since. Early in the 1970s, we began transplanting younger and younger children. After attempting four kidney transplants in children under the age of 1 using deceased infant donors to obtain an appropriate size match, we unfortunately observed early rejection. All four kidney grafts were lost. It soon became apparent that such young infants possessed protective antibodies that resulted in rejection, despite our immunosuppression, which at that time included Imuran, prednisone, and Minnesota antilymphocyte globulin (MALG). Thus, we turned our attention to living related donors, whose kidney would present a lesser immunologic challenge to the recipient. Of course, only adults (such as parents or grandparents) could possibly be donors. Thus, it was important to develop surgical and
3593
metabolic techniques for transplanting these large adult kidneys into small infants. Once we did, we began transplanting adult kidneys (typically from parents or grandparents) into infants, resulting in a very successful program in pediatric kidney transplantation.4 We have now performed kidney transplants in about 900 children, including 50 under the age of 1 and more than 250 under the age of 2: living donors have been used in 80% of these transplants. Currently, the United Network for Organ Sharing (UNOS) reports5 only a slight increase in available deceased donors: from 10,000 in 1988 to 15,000 in 2002. The solid-organ transplant waiting list, however, grew from 10,000 in 1988 to almost 90,000 in 2002. Clearly, we must reexamine other sources of organs. For the same period, the use of living donors grew from 2000 in 1988 to more than 6000 in 2002; living donors now represent 50% of all donors. Kidney graft survival in terms of half-life (T1/2) reflects the advantage of living donors: T1/2 is now 40 years with a 3-haplotype identical sibling donor, 16 years with a 1-haplotype sibling donor, and more than 16 years with a living unrelated donor. In contrast, T1/2 is now only 10 years with a deceased donor. Here, in addition to our frequent use of living related donors, we have increased our use of living unrelated donors (usually a spouse, distant family relative, friend, or fellow church member). Thus, the primary increase in donor availability recently has come from the use of living unrelated donors. In addition, a novel intervention that we have used since 1997 is nondirected organ donation.6 Nondirected organs come from individuals who want to donate a kidney ⬎to a pool (not directing it to any known individual or to any specific gender, race, or religion). We have now performed 30 nondirected living donor kidney transplants. All of our living donors are instructed about the possible medical benefit to themselves of the donor evaluation: the screening process they undergo may yield previously unrecognized problems. In our own experience, the donor screening has uncovered cases of unsuspected diabetes, hypertension, abnormal renal function, cardiovascular disease, and six malignancies (which were all removed in curative resections). In addition, donation confers psychological benefits. However, living donation also carries possible risks. Presently, in our own series, as well as in others, the mortality rate for living kidney donors is 0.03%; morbidity, 0.2%.7 Most of the postoperative complications are minor and transient. In addition, we have studied the long-term results of having a nephrectomy. Studies in the 1960s, primarily in the Danish literature,8 showed that the 25-year survival curve of individuals with one kidney was equivalent to that of agematched controls with two kidneys. Many studies since then have also determined that there is no adverse impact, even 10 to 20 years after kidney donation. In our own studies,9 we find no difference in renal function, blood pressure, or the percentage of individuals with proteinuria. Finally, the most important aspect of living donor transplants is to make absolutely every effort to ensure that the donor is in optimal physical condition. We do not accept a
3594
donor who has an underlying adverse physical condition or who is on medications for hypertension or for any other reason. If these high standards are met, then a successful living donor program can be accomplished. Living donors almost always experience a boost in selfesteem, a heightened quality of life, and an increased sense of well-being. In our surveys,10 96% felt that donation was a positive experience. Given the operative mortality rate of 0.03%, low postoperative morbidity rate of 0.2%, and enhanced quality of life, we conclude that living donation (whether related or not) appears to be the best possible source of organs at the present time. Having said that, I just returned from Spain, where the deceased donor program is very successful, but where the living donor program unfortunately accounts for fewer than 10% of their total kidney transplants. I’m pleased to add that, little by little, most of Europe is coming around to living donor transplants, as did most of the Scandinavian countries early on.
NAJARIAN
REFERENCES 1. Murray JE, Merrill JP, Harrison JH: Kidney transplantation between seven pairs of identical twins. Ann Surg 148:343, 1958 2. Belzer FO, Ashby BS, Dunphy JE: 24-hour and 72-hour preservation of canine kidneys. Lancet 2:536, 1967 3. Collins GM, Bravo-Sugarman M, Tersaki PI: Kidney preservation for transplantation. Lancet 1:1219, 1969 4. DeShazo CV, Simmons RL, Bernstein DM, et al: Results of renal transplantation in 100 children. Surgery 75:461, 1974 5. Cecka MJ, Terasaki PI (eds): Clinical Transplants 2003. Los Angeles, Calif: UCLA Immunogenetics Center; 2003 6. Jacobs C, Roman D, Garvey C, et al: Twenty-two nondirected kidney donors: an update on a single center’s experience. Am J Transpl 4:1110, 2004 7. Bia MJ, et al: Evaluation of living renal donors. Transplantation 60:322, 1995 8. Anderson B, et al: Scand J Urol Nephrol 2:91, 1968 9. Kasiske BL, Ma JZ, Louis TA, et al: Long-term effects of reduced renal mass in humans. Kidney Intern 48:814, 1995 10. Johnson EM, Anderson JK, Jacobs C, et al: Long-term follow-up of living kidney donors: quality of life after kidney donation. Transplantation 67:717, 1999
M
Y INTEREST in and advocacy for living donor kidney transplants began in 1963 when I performed my first clinical kidney transplant in San Francisco. It was obvious from the first identical twin transplant (Boston, 1954)1 that living donor transplants were likely to be more convenient and successful than deceased donor transplants. This continued to be true even for nonidentical twin transplants, with Imuran and prednisone as the only immunosuppressive agents. From the outset, immediate and late results were more favorable with living related donor transplants. Moreover, the use of organs from deceased donors initially presented a difficult logistical challenge. For the most part, deceased donor transplants in the early days required that the recipient be in the university hospital awaiting the possible
availability of an organ, which usually came from a separate hospital or trauma unit and had to be transported. This logistical challenge fueled our enthusiasm for attempting to persuade recipients to find living related donors whenever possible. In 1966, after Dr. Folkert Belzer had completed his residency at the University of Oregon and was appointed a junior staff surgeon at the University of California-San Francisco (UCSF), I was asked by our chairman, Dr. Bert Dunphy, to find a suitable research project for Dr. Belzer. His primary interest was in vascular surgery; he had virtually no training in immunology. I suggested that his project From the Department of Surgery, Fairview-University Medical Center, Minneapolis, Minnesota.
0041-1345/05/$–see front matter doi:10.1016/j.transproceed.2005.10.079
© 2005 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
3592
Transplantation Proceedings, 37, 3592–3594 (2005)
LIVING DONOR KIDNEY TRANSPLANTS
in our transplantation laboratory could be to explore the possibilities of developing a technique for preserving kidneys from deceased donors. Short-term preservation would allow prospective recipients to remain at home until a deceased donor kidney became available. Furthermore, adequate time would be provided pretransplant for appropriate tissue typing of the donor kidney. Dr. Belzer pursued this investigation in our laboratory. By serendipity, he eventually came up with a solution that would allow short-term preservation of a kidney for transplantation. One afternoon, after he had bled a series of dogs to obtain plasma for his kidney perfusion experiments, he was unable to use the plasma immediately and instead placed it in a refrigerator overnight. The next morning, he found that a layer of flocculation had formed in the plasma, which turned out to consist of lipids. He then filtered the plasma to remove the flocculent layer, so that the resultant clear plasma could be used for kidney perfusion. This “cryoprecipitated” plasma readily perfused the kidney without obstruction. In the past, perfusion of freshly drawn, unaltered plasma through the kidney had invariably resulted in vascular obstruction in the cold kidneys. Subsequently, he developed a pumping mechanism, thereby establishing perfusion preservation. This research (done in 1966) was published in the Lancet in 1967.2 Shortly thereafter, Dr. Jeffrey Collins3 of the University of California-Los Angeles (UCLA) developed a perfusion solution now known as Collins Solution that could be used to preserve kidneys for 12 hours at 0°C; eventually, it permitted cold storage of kidneys for up to 2 days. With kidneys that could be stored for 12 or more hours, simple transportation from one institution to another was now possible. Thanks to the Belzer technique and the Collins Solution, the logistical difficulties of deceased donor kidney transplantation were primarily overcome. However, living related kidneys, when available, remained our first choice. On arriving at the University of Minnesota in 1967, I was pleasantly surprised to find that strong family ties in that state meant that a number of family members would frequently come forward as a possible kidney donor for a loved one in renal failure. In the Minnesota transplant program, living donation quickly increased to represent over 65% of our donors. It has remained at well over 50% since. Early in the 1970s, we began transplanting younger and younger children. After attempting four kidney transplants in children under the age of 1 using deceased infant donors to obtain an appropriate size match, we unfortunately observed early rejection. All four kidney grafts were lost. It soon became apparent that such young infants possessed protective antibodies that resulted in rejection, despite our immunosuppression, which at that time included Imuran, prednisone, and Minnesota antilymphocyte globulin (MALG). Thus, we turned our attention to living related donors, whose kidney would present a lesser immunologic challenge to the recipient. Of course, only adults (such as parents or grandparents) could possibly be donors. Thus, it was important to develop surgical and
3593
metabolic techniques for transplanting these large adult kidneys into small infants. Once we did, we began transplanting adult kidneys (typically from parents or grandparents) into infants, resulting in a very successful program in pediatric kidney transplantation.4 We have now performed kidney transplants in about 900 children, including 50 under the age of 1 and more than 250 under the age of 2: living donors have been used in 80% of these transplants. Currently, the United Network for Organ Sharing (UNOS) reports5 only a slight increase in available deceased donors: from 10,000 in 1988 to 15,000 in 2002. The solid-organ transplant waiting list, however, grew from 10,000 in 1988 to almost 90,000 in 2002. Clearly, we must reexamine other sources of organs. For the same period, the use of living donors grew from 2000 in 1988 to more than 6000 in 2002; living donors now represent 50% of all donors. Kidney graft survival in terms of half-life (T1/2) reflects the advantage of living donors: T1/2 is now 40 years with a 3-haplotype identical sibling donor, 16 years with a 1-haplotype sibling donor, and more than 16 years with a living unrelated donor. In contrast, T1/2 is now only 10 years with a deceased donor. Here, in addition to our frequent use of living related donors, we have increased our use of living unrelated donors (usually a spouse, distant family relative, friend, or fellow church member). Thus, the primary increase in donor availability recently has come from the use of living unrelated donors. In addition, a novel intervention that we have used since 1997 is nondirected organ donation.6 Nondirected organs come from individuals who want to donate a kidney ⬎to a pool (not directing it to any known individual or to any specific gender, race, or religion). We have now performed 30 nondirected living donor kidney transplants. All of our living donors are instructed about the possible medical benefit to themselves of the donor evaluation: the screening process they undergo may yield previously unrecognized problems. In our own experience, the donor screening has uncovered cases of unsuspected diabetes, hypertension, abnormal renal function, cardiovascular disease, and six malignancies (which were all removed in curative resections). In addition, donation confers psychological benefits. However, living donation also carries possible risks. Presently, in our own series, as well as in others, the mortality rate for living kidney donors is 0.03%; morbidity, 0.2%.7 Most of the postoperative complications are minor and transient. In addition, we have studied the long-term results of having a nephrectomy. Studies in the 1960s, primarily in the Danish literature,8 showed that the 25-year survival curve of individuals with one kidney was equivalent to that of agematched controls with two kidneys. Many studies since then have also determined that there is no adverse impact, even 10 to 20 years after kidney donation. In our own studies,9 we find no difference in renal function, blood pressure, or the percentage of individuals with proteinuria. Finally, the most important aspect of living donor transplants is to make absolutely every effort to ensure that the donor is in optimal physical condition. We do not accept a
3594
donor who has an underlying adverse physical condition or who is on medications for hypertension or for any other reason. If these high standards are met, then a successful living donor program can be accomplished. Living donors almost always experience a boost in selfesteem, a heightened quality of life, and an increased sense of well-being. In our surveys,10 96% felt that donation was a positive experience. Given the operative mortality rate of 0.03%, low postoperative morbidity rate of 0.2%, and enhanced quality of life, we conclude that living donation (whether related or not) appears to be the best possible source of organs at the present time. Having said that, I just returned from Spain, where the deceased donor program is very successful, but where the living donor program unfortunately accounts for fewer than 10% of their total kidney transplants. I’m pleased to add that, little by little, most of Europe is coming around to living donor transplants, as did most of the Scandinavian countries early on.
NAJARIAN
REFERENCES 1. Murray JE, Merrill JP, Harrison JH: Kidney transplantation between seven pairs of identical twins. Ann Surg 148:343, 1958 2. Belzer FO, Ashby BS, Dunphy JE: 24-hour and 72-hour preservation of canine kidneys. Lancet 2:536, 1967 3. Collins GM, Bravo-Sugarman M, Tersaki PI: Kidney preservation for transplantation. Lancet 1:1219, 1969 4. DeShazo CV, Simmons RL, Bernstein DM, et al: Results of renal transplantation in 100 children. Surgery 75:461, 1974 5. Cecka MJ, Terasaki PI (eds): Clinical Transplants 2003. Los Angeles, Calif: UCLA Immunogenetics Center; 2003 6. Jacobs C, Roman D, Garvey C, et al: Twenty-two nondirected kidney donors: an update on a single center’s experience. Am J Transpl 4:1110, 2004 7. Bia MJ, et al: Evaluation of living renal donors. Transplantation 60:322, 1995 8. Anderson B, et al: Scand J Urol Nephrol 2:91, 1968 9. Kasiske BL, Ma JZ, Louis TA, et al: Long-term effects of reduced renal mass in humans. Kidney Intern 48:814, 1995 10. Johnson EM, Anderson JK, Jacobs C, et al: Long-term follow-up of living kidney donors: quality of life after kidney donation. Transplantation 67:717, 1999