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Approaches to the organ donor shortage1
Transplantation Approaches to the Organ Donor Shortage Guest Reviewer: John C. McDonald, MD REVIEWER COMMENTS
This is a good study demonstrating that the donor pool can be expanded by transplanting 2 kidneys from a donor whose renal function is too compromised to sustain 2 recipients into a single recipient. This policy increased the number of cadaver donor renal transplants performed by the Stanford group by 21% during the period of study. All dual-kidney donors had been turned down as conventional donors by all the centers in their sharing region. Thus, virtually none of these kidneys would have been used if not for this protocol. There are some disadvantages to this concept. It requires essentially 2 operations on each recipient, with the attendant increased morbidity as well as increased cost and use of resources. Also, it is possible that single kidneys from some of these donors could support some small recipients. Nevertheless, kidneys from hypertensive, elderly donors with reduced renal function are being discarded across the country with some frequency. The use of 2 kidneys for a single recipient in this context is sensible and deserves wider use.
DUAL KIDNEY TRANSPLANTATION: OLDER DONORS FOR OLDER RECIPIENTS. Lee CM, Carter JT, Weinstein RJ, et al. J Am Coll Surg 1999;189:82–92. Objective: To determine if the transplantation of both kidneys from a marginal or
so-called expanded criteria donor will yield satisfactory results. Design: A retrospective comparison of donor and recipient data between recipients of dual (n ⫽ 41) and single (n ⫽ 199) cadaveric renal transplants from February 1, 1995 to March 22, 1998. Setting: Stanford University School of Medicine, Stanford, California. Methods: The study group was 41 patients who each received dual renal transplants
from high-risk donors. Donors and recipients were matched for size and age. The kidneys from each donor had been refused for single transplants by all centers in their organ procurement area. All donors were older than 60 years and had a creatinine clearance of less than 90 ml/min or an elevated terminal serum creatinine. The results were compared to those obtained from 199 recipients of single transplants during the same time period. Results: Recipients of dual kidneys had donors who were older than single-kidney
donors (59 ⫾ 12 vs 42 ⫾ 17 years, respectively, p ⬍ 0.0001) and had more hypertension (51% vs 29%, p ⫽ 0.024). Average urine output was lower in the dual-kidney group (252 ⫾ 157 vs 191 ⫾ 70 ml/h, p ⫽ 0.036). Donors for dual-kidney recipients had a lower donor admission creatinine clearance of 82 ⫾ 28 ml/min versus 105 ⫾ 45 ml/min in the single-kidney group (p ⫽ 0.005). Recipients of dual kidneys were older (58 ⫾ 11 vs 47 ⫾ 12 years, p ⱖ 0.0001). Dual- and single-kidney recipients had similar serum creatinines up to 2 years posttransplant (1.6 ⫾ 0.3 vs 1.6 ⫾ 0.7 mg/dl at 2 years, p ⫽ not significant [NS]), a comparable incidence of delayed graft function (24% vs 33%, p ⫽ NS), and 3-month–posttransplant creatinine clearance (54 ⫾ 23 vs 57 ⫾ 25 ml/min, p ⫽ NS). One-year patient and graft survival were 97% and 90%, respectively, for single-kidney transplantation and 98% and 89% for dual-kidney transplantation (p ⫽ NS).
Conclusions: Dual-kidney donors were significantly older and had more hypertension, lower urine outputs, and lower donor admission creatinine clearance. Despite these differences, dual-kidney recipients had postoperative function, outcomes, and survival comparable to those of single-kidney recipients. We believe selective use of dual-kidney transplantation can provide excellent outcomes in recipients of kidneys from older donors with reduced renal function. REVIEWER COMMENTS
This article reflects great experience with non– heart beating cadaver kidneys from a single institution and demonstrates without doubt that many kidneys can be obtained in this fashion and provide good renal function for long periods. This is certainly a means of expanding
THE FATE OF 359 RENAL ALLOGRAFTS HARVESTED FROM NON-HEART BEATING CADAVER DONORS AT A SINGLE CENTER. Hoshinaga K, Shiroki R, Fujita T, Kanno T, Naide Y. Clin Transpl 1998;213–220. Objective: To evaluate the usefulness of non– heart beating cadavers as a source of kidneys for transplantation. Design: A retrospective review of the results obtained with 359 kidneys obtained from non– heart beating cadavers from a single institution.
CURRENT SURGERY • Volume 57/Number 5 • September/October 2000
427
Setting: Fujita Health University, Nagoya, Japan.
REVIEWER COMMENTS (Con’t)
Participants: One hundred eighty-one cardiac arrest kidney donors.
the donor supply. There are some peculiar findings from the study. Why there were poorer results when donors had CVD has to be determined by finding out what factors (ie, age, hypertension, etc) are important. The long-term outcome from these kidneys with delayed function is unexpected, because many studies have related the need for dialysis posttransplant to a poorer long-term outcome. Nevertheless, this technology is clearly an important method of expanding the donor supply.
Methods: Donor families were approached for permission for organ removal either
after brain death was diagnosed or after unsuccessful resuscitation after cardiac arrest. After consent was obtained, a triple-lumen catheter with 2 balloons was inserted through the femoral artery and a single-lumen catheter was placed in the femoral vein. When death occurred by cardiac arrest, the 2 balloons were inflated, thus isolating the aorta above and below the renal arteries. In situ cooling was begun with cold solutions. The kidneys were then removed in the operating room and preserved by hypothermia. Kidneys were removed from 181 donors. The causes of death were cerebrovascular disease (CVD) in 114 and non-CVD in 67. Donor age ranged from 7 months to 70 years. Results: Thirty-five of 359 kidneys retrieved were discarded for various reasons, and
324 transplanted. Before 1983, 29 grafts were transplanted into recipients treated with azathioprine and steroids. These grafts had a high incidence of primary nonfunction (20.5%). Subsequently recipients were treated with cyclosporine or tacrolimus and steroids, and statistical analysis was based on these 285 grafts. Warm ischemia times ranged from 1 to 71 minutes (mean 13.2 minutes). In situ ischemia time ranged from 35 to 137 minutes (mean 77.9 minutes). Total ischemia time ranged from 4 hours 4 minutes to 43 hours 23 minutes (mean 11 hours 45 minutes). None of these times were statistically important in long-term results. Immediate function occurred in 16.1%, delayed function in 77.9%, and primary nonfunction in 6.0%. There was a correlation between the posttransplant dialysis period and the lowest serum creatinine achieved. The quality of renal function ultimately obtained was correlated with donor age and cause of death, being better when donors were younger and when the cause of death was not CVD. In spite of these findings, longterm graft survival was reported as comparable to results in the United States with heart-beating cadaver donors and in Japan with living donors. Conclusions: Renal grafts harvested from non– heart beating cadavers using an in
situ cooling technique can recover good renal function and provide excellent long-term graft survival, especially when the donor is young and the cause of death is not CVD.
LIVING UNRELATED RENAL DONATION: THE UNIVERSITY OF WISCONSIN EXPERIENCE. D’Alessandro A, Pirsch J, Knechtle S, et al. Surgery 1998;124: 604 – 611. Objective: To examine the long-term results of 150 living unrelated renal donations
(LURDs) performed at 1 center during a 16-year period. Design: A retrospective multifactorial review of results of kidney allografts obtained
from LURDs. Setting: University of Wisconsin tertiary care center, Madison, Wisconsin. Participants: All patients receiving renal transplants during the study period at the
University of Wisconsin. Methods: From December 23, 1981 to February 1998, 150 LURDs, 219 HLA
identical, 577 haploidentical, and 1789 cadaveric kidney transplant procedures were performed. Surgical complications, rejection episodes, infectious complications, and the cause of graft loss and death were examined. Ten-year patient and graft survival rates were compared between groups.
REVIEWER COMMENTS
This article draws on probably the greatest experience of a single center with LURD kidney transplantation. Although rejection episodes seem high, this is probably because the study period covered 17 years. It would be less with current therapy. The long-term graft survival rate is surprisingly better than that of cadaveric donation. This lends credence to the concept that long-term success is related, in part, to the health of the organ at the time of implantation. The use of unrelated living donors has been widely accepted within the transplant community and is now a standard of practice.
Results: In LURDs the usual group of complications was observed. Rejection oc-
curred 123 times in 78 patients (52%), and 66 patients (44%) had 1 or more infec428
CURRENT SURGERY • Volume 57/Number 5 • September/October 2000
tions. Thirty-six allografts were lost, and 25 recipient deaths occurred. Allograft survival rates at 10 years for HLA identicals, haploidenticals, LURDs, and cadaver transplant procedures were 75%, 59%, 56%, and 44%, respectively. Conclusions: Long-term LURD allograft survival rates are lower than those for HLA-identical kidney transplantation, but equivalent to those of haploidentical kidney transplantation and better than those of cadaveric kidney transplantation. Spousal and nonspousal LURDs should be actively encouraged to help alleviate the current donor kidney shortage.
REVIEWER SUMMARY The shortage of organs for donation has become a national crisis. There are almost 70,000 patients now on the United States national list waiting for some organ. In 1998 about 4800 individuals died while on the list awaiting a lifesaving transplant. This crisis has created a great sense of urgency to find additional sources of transplantable organs. In this review I have concentrated on 3 efforts: the use of dual kidneys from donors whose kidneys would not otherwise be used, the use of non– heart beating cadavers, and the use of unrelated living donors. All of these are useful means of obtaining more organs, especially kidneys. However, pilot studies of the use of non– heart beating donors of livers are promising. All of these approaches need further refinement. The use of living donors of liver is now being expanded,1 and improved laparoscopic technology has greatly increased the willingness of living individuals to donate kidneys, because it is less morbid and loss of work is reduced.2 These are important initiatives, but we must remember that less than a third of patients who die in a way that would allow them to be organ donors actually become organ donors. Mostly this is because their survivors will not consent to donation. Convincing the population that the moral course of action for anyone dying with transplantable organs is to have the organs transplanted remains our greatest challenge.
JOHN C. MCDONALD, MD Department of Surgery Louisiana State University Health Sciences Center Shreveport, Louisiana PII S0149-7944(00)00250-6
REFERENCES 1. Lo C, Fan S, Liu C, et al. Applicability of living donor liver transplantation to
high-urgency patients. Transplantation 1999;67:73–77. 2. Ratner LK, Montgomery R, Kavoussi L. Laparoscopic live donor nephrectomy: the
four year Johns Hopkins University experience. Nephrol Dial Transplant 1999;14: 2090 –2093.
Transplantation Pediatric Liver Transplantation: Trends in Liver Transplantation in Children Guest Reviewers: Thomas D. Johnston, MD, Kunam S. Reddy, MD, Dinesh Ranjan, MD, and Robert M. Mentzer, Jr, MD CURRENT SURGERY • Volume 57/Number 5 • September/October 2000
429
This is a good study demonstrating that the donor pool can be expanded by transplanting 2 kidneys from a donor whose renal function is too compromised to sustain 2 recipients into a single recipient. This policy increased the number of cadaver donor renal transplants performed by the Stanford group by 21% during the period of study. All dual-kidney donors had been turned down as conventional donors by all the centers in their sharing region. Thus, virtually none of these kidneys would have been used if not for this protocol. There are some disadvantages to this concept. It requires essentially 2 operations on each recipient, with the attendant increased morbidity as well as increased cost and use of resources. Also, it is possible that single kidneys from some of these donors could support some small recipients. Nevertheless, kidneys from hypertensive, elderly donors with reduced renal function are being discarded across the country with some frequency. The use of 2 kidneys for a single recipient in this context is sensible and deserves wider use.
DUAL KIDNEY TRANSPLANTATION: OLDER DONORS FOR OLDER RECIPIENTS. Lee CM, Carter JT, Weinstein RJ, et al. J Am Coll Surg 1999;189:82–92. Objective: To determine if the transplantation of both kidneys from a marginal or
so-called expanded criteria donor will yield satisfactory results. Design: A retrospective comparison of donor and recipient data between recipients of dual (n ⫽ 41) and single (n ⫽ 199) cadaveric renal transplants from February 1, 1995 to March 22, 1998. Setting: Stanford University School of Medicine, Stanford, California. Methods: The study group was 41 patients who each received dual renal transplants
from high-risk donors. Donors and recipients were matched for size and age. The kidneys from each donor had been refused for single transplants by all centers in their organ procurement area. All donors were older than 60 years and had a creatinine clearance of less than 90 ml/min or an elevated terminal serum creatinine. The results were compared to those obtained from 199 recipients of single transplants during the same time period. Results: Recipients of dual kidneys had donors who were older than single-kidney
donors (59 ⫾ 12 vs 42 ⫾ 17 years, respectively, p ⬍ 0.0001) and had more hypertension (51% vs 29%, p ⫽ 0.024). Average urine output was lower in the dual-kidney group (252 ⫾ 157 vs 191 ⫾ 70 ml/h, p ⫽ 0.036). Donors for dual-kidney recipients had a lower donor admission creatinine clearance of 82 ⫾ 28 ml/min versus 105 ⫾ 45 ml/min in the single-kidney group (p ⫽ 0.005). Recipients of dual kidneys were older (58 ⫾ 11 vs 47 ⫾ 12 years, p ⱖ 0.0001). Dual- and single-kidney recipients had similar serum creatinines up to 2 years posttransplant (1.6 ⫾ 0.3 vs 1.6 ⫾ 0.7 mg/dl at 2 years, p ⫽ not significant [NS]), a comparable incidence of delayed graft function (24% vs 33%, p ⫽ NS), and 3-month–posttransplant creatinine clearance (54 ⫾ 23 vs 57 ⫾ 25 ml/min, p ⫽ NS). One-year patient and graft survival were 97% and 90%, respectively, for single-kidney transplantation and 98% and 89% for dual-kidney transplantation (p ⫽ NS).
Conclusions: Dual-kidney donors were significantly older and had more hypertension, lower urine outputs, and lower donor admission creatinine clearance. Despite these differences, dual-kidney recipients had postoperative function, outcomes, and survival comparable to those of single-kidney recipients. We believe selective use of dual-kidney transplantation can provide excellent outcomes in recipients of kidneys from older donors with reduced renal function. REVIEWER COMMENTS
This article reflects great experience with non– heart beating cadaver kidneys from a single institution and demonstrates without doubt that many kidneys can be obtained in this fashion and provide good renal function for long periods. This is certainly a means of expanding
THE FATE OF 359 RENAL ALLOGRAFTS HARVESTED FROM NON-HEART BEATING CADAVER DONORS AT A SINGLE CENTER. Hoshinaga K, Shiroki R, Fujita T, Kanno T, Naide Y. Clin Transpl 1998;213–220. Objective: To evaluate the usefulness of non– heart beating cadavers as a source of kidneys for transplantation. Design: A retrospective review of the results obtained with 359 kidneys obtained from non– heart beating cadavers from a single institution.
CURRENT SURGERY • Volume 57/Number 5 • September/October 2000
427
Setting: Fujita Health University, Nagoya, Japan.
REVIEWER COMMENTS (Con’t)
Participants: One hundred eighty-one cardiac arrest kidney donors.
the donor supply. There are some peculiar findings from the study. Why there were poorer results when donors had CVD has to be determined by finding out what factors (ie, age, hypertension, etc) are important. The long-term outcome from these kidneys with delayed function is unexpected, because many studies have related the need for dialysis posttransplant to a poorer long-term outcome. Nevertheless, this technology is clearly an important method of expanding the donor supply.
Methods: Donor families were approached for permission for organ removal either
after brain death was diagnosed or after unsuccessful resuscitation after cardiac arrest. After consent was obtained, a triple-lumen catheter with 2 balloons was inserted through the femoral artery and a single-lumen catheter was placed in the femoral vein. When death occurred by cardiac arrest, the 2 balloons were inflated, thus isolating the aorta above and below the renal arteries. In situ cooling was begun with cold solutions. The kidneys were then removed in the operating room and preserved by hypothermia. Kidneys were removed from 181 donors. The causes of death were cerebrovascular disease (CVD) in 114 and non-CVD in 67. Donor age ranged from 7 months to 70 years. Results: Thirty-five of 359 kidneys retrieved were discarded for various reasons, and
324 transplanted. Before 1983, 29 grafts were transplanted into recipients treated with azathioprine and steroids. These grafts had a high incidence of primary nonfunction (20.5%). Subsequently recipients were treated with cyclosporine or tacrolimus and steroids, and statistical analysis was based on these 285 grafts. Warm ischemia times ranged from 1 to 71 minutes (mean 13.2 minutes). In situ ischemia time ranged from 35 to 137 minutes (mean 77.9 minutes). Total ischemia time ranged from 4 hours 4 minutes to 43 hours 23 minutes (mean 11 hours 45 minutes). None of these times were statistically important in long-term results. Immediate function occurred in 16.1%, delayed function in 77.9%, and primary nonfunction in 6.0%. There was a correlation between the posttransplant dialysis period and the lowest serum creatinine achieved. The quality of renal function ultimately obtained was correlated with donor age and cause of death, being better when donors were younger and when the cause of death was not CVD. In spite of these findings, longterm graft survival was reported as comparable to results in the United States with heart-beating cadaver donors and in Japan with living donors. Conclusions: Renal grafts harvested from non– heart beating cadavers using an in
situ cooling technique can recover good renal function and provide excellent long-term graft survival, especially when the donor is young and the cause of death is not CVD.
LIVING UNRELATED RENAL DONATION: THE UNIVERSITY OF WISCONSIN EXPERIENCE. D’Alessandro A, Pirsch J, Knechtle S, et al. Surgery 1998;124: 604 – 611. Objective: To examine the long-term results of 150 living unrelated renal donations
(LURDs) performed at 1 center during a 16-year period. Design: A retrospective multifactorial review of results of kidney allografts obtained
from LURDs. Setting: University of Wisconsin tertiary care center, Madison, Wisconsin. Participants: All patients receiving renal transplants during the study period at the
University of Wisconsin. Methods: From December 23, 1981 to February 1998, 150 LURDs, 219 HLA
identical, 577 haploidentical, and 1789 cadaveric kidney transplant procedures were performed. Surgical complications, rejection episodes, infectious complications, and the cause of graft loss and death were examined. Ten-year patient and graft survival rates were compared between groups.
REVIEWER COMMENTS
This article draws on probably the greatest experience of a single center with LURD kidney transplantation. Although rejection episodes seem high, this is probably because the study period covered 17 years. It would be less with current therapy. The long-term graft survival rate is surprisingly better than that of cadaveric donation. This lends credence to the concept that long-term success is related, in part, to the health of the organ at the time of implantation. The use of unrelated living donors has been widely accepted within the transplant community and is now a standard of practice.
Results: In LURDs the usual group of complications was observed. Rejection oc-
curred 123 times in 78 patients (52%), and 66 patients (44%) had 1 or more infec428
CURRENT SURGERY • Volume 57/Number 5 • September/October 2000
tions. Thirty-six allografts were lost, and 25 recipient deaths occurred. Allograft survival rates at 10 years for HLA identicals, haploidenticals, LURDs, and cadaver transplant procedures were 75%, 59%, 56%, and 44%, respectively. Conclusions: Long-term LURD allograft survival rates are lower than those for HLA-identical kidney transplantation, but equivalent to those of haploidentical kidney transplantation and better than those of cadaveric kidney transplantation. Spousal and nonspousal LURDs should be actively encouraged to help alleviate the current donor kidney shortage.
REVIEWER SUMMARY The shortage of organs for donation has become a national crisis. There are almost 70,000 patients now on the United States national list waiting for some organ. In 1998 about 4800 individuals died while on the list awaiting a lifesaving transplant. This crisis has created a great sense of urgency to find additional sources of transplantable organs. In this review I have concentrated on 3 efforts: the use of dual kidneys from donors whose kidneys would not otherwise be used, the use of non– heart beating cadavers, and the use of unrelated living donors. All of these are useful means of obtaining more organs, especially kidneys. However, pilot studies of the use of non– heart beating donors of livers are promising. All of these approaches need further refinement. The use of living donors of liver is now being expanded,1 and improved laparoscopic technology has greatly increased the willingness of living individuals to donate kidneys, because it is less morbid and loss of work is reduced.2 These are important initiatives, but we must remember that less than a third of patients who die in a way that would allow them to be organ donors actually become organ donors. Mostly this is because their survivors will not consent to donation. Convincing the population that the moral course of action for anyone dying with transplantable organs is to have the organs transplanted remains our greatest challenge.
JOHN C. MCDONALD, MD Department of Surgery Louisiana State University Health Sciences Center Shreveport, Louisiana PII S0149-7944(00)00250-6
REFERENCES 1. Lo C, Fan S, Liu C, et al. Applicability of living donor liver transplantation to
high-urgency patients. Transplantation 1999;67:73–77. 2. Ratner LK, Montgomery R, Kavoussi L. Laparoscopic live donor nephrectomy: the
four year Johns Hopkins University experience. Nephrol Dial Transplant 1999;14: 2090 –2093.
Transplantation Pediatric Liver Transplantation: Trends in Liver Transplantation in Children Guest Reviewers: Thomas D. Johnston, MD, Kunam S. Reddy, MD, Dinesh Ranjan, MD, and Robert M. Mentzer, Jr, MD CURRENT SURGERY • Volume 57/Number 5 • September/October 2000
429