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Results of single kidneys from donors aged 9 to 60 months: Results in 144 adult recipients
ELSEVIER
Results of Single Kidneys From Donors Aged 9 to 60 Months: Results in 144 Adult Recipients L.H. Banowsky,
J. Lackner,
R. Kothmann,
and F.H. Wright
T
HE INCREASING disparity between the number of potential recipients awaiting an organ transplant and the number of available cadaveric donor organs is the major problem in clinical transplantation today. Over 36,000 persons are currently awaiting kidney transplantation; while only 503.5 cadaveric donors were available in 1996. The renal waiting list has never decreased and has consistently grown larger each year. Liberalized acceptance criteria to include older donors, donors with medical conditions such as hypertension and diabetes, and donors with less than ideal renal function has resulted in some increase in organ recovery. The use of kidneys from donors over the age of 55 years has gained increased acceptance nationally and these donors have gone from 11% of the total in 1988 to 19% of the total for 1995.’ In contrast, the use of kidneys from pediatric donors younger than 5 years old has not increased and has not been promoted by the transplant community as an important source of cadaveric kidneys. United Network for Organ Sharing (UNOS) data have shown a decrease in pediatric donors from 330 (8.1% of total donors) in 1988 to 314 (5.9% of total donors) in 1995.’ From these donors, only 218 patients received renal transplants in 1988, indicating that 34% of the donors were not used and only 33% of the potential single-kidney utilization was achieved. This had marginally improved in 1995, with 231 patients receiving transplants, but still failing to use kidneys from some 24% of donors and reaching only 37% of the potential singlekidney utilization.’ This paper will report the San Antonio Community Hospital experience in transplanting single kidneys from donors younger than 4 years of age into adult recipients in 142 cases. Patient and allograft survival and renal function in these 142 transplants will be compared with UNOS data for transplants from donors 16 to 55 years of age, donors older than 55 years, and with reported en bloc transplants from donors younger than 5 years of age. A case will be made for increased recovery and utilization of kidneys from young donors. MATERIALS
AND
METHODS
From January 1986 through December 1996, 142 kidneys from cadaveric donors younger than 4 years of age were transplanted as single organs into adult recipients. Kidneys were allocated by
0 1997 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010 Transplantation
Proceedings,
29, 32713273
(1997)
Table 1. Donor and Recipient Characteristics Donor Characteristics Age: Mean = 23 mo 9-12 mo (n = 19) 13-24 mo (n = 74) 25-48 mo (n = 49) Weight: mean 27 lb (Q-51 lb) CMV Positive: 44% Preservation time: mean 37 h (18-52 h)
RecipientCharacteristics
Age: mean 41.2 y (16-66 y) Sex: 74 male and 68 female Weight: 136 lb (75-l 86 lb) Diabetes mellitus: 26% Previous transplant: 12% PRA: mean 12% (O-100%) 0 MM or 6-antigen: 7 (4.9%)
Abbreviations:CMV, cytomegalovirus,PRA, panel reactive antibody.
UNOS criteria with the stipulation that for medical reasons, recipient weight would be limited to approximately 160 lb. Unlike other series reported, no effort was made to exclude repeat transplants, sensitized patients, diabetics, or other potentially highrisk groups.’ Donor and recipient characteristics are shown in Table 1. The immunosuppressive regimens used from 1986 to 1989 and from 1990 to 1995 have been previously reported.3.4 In 1995, the regimen used from 1990 to 1995 was modified as follows: alternate patients received cyclosporine (CyA) or FK 506 and mycophenalate mofetil was used in all patients rather than azathioprine. Surgical technique has remained the same throughout the entire series and has been previously reported.5 Kidneys with single and multiple arteries were used as long as an aortic patch was available; failure of the donor surgeon to include a minimal aortic patch precluded use of the kidney. The venous anastomosis was done using an interrupted suture technique. Urinary reconstruction was by stented ureteroureterostomy or ureteropyeloneostomy. Patient follow-up included transplant renal ultrasound studies and calculation of renal volume on postoperative day 1 and at 1,3, 6, and 12 months. Serum creatinine and hematocrit levels were also obtained at these times. Allograft failure was defined as a return to chronic dialysis therapy or as any death with a functioning transplant. A patient death was considered as any death within 6 months of returning to chronic dialysis, or any death related to the transplant operation or immunosuppressive drugs. Calculation of actuarial patient and
From the Transplant Department, San Antonio Community Hospital, San Antonio, Texas, USA. Address reprint requests to Dr F.H. Wright, San Antonio Community Hospital, Transplant Dept, 8026 Floyd Curl Drive, San Antonio, TX 78229, USA.
0041-l 345/97/$17.00 PII so041 -1345(97)00907-X
3271
3272
BANOWSKY,
.‘..A 75 +
-.,.--
w
-
‘G
0” 50 B *
_
_-----
..‘.‘.........,
s
-7,
t-
--
Donor Age
---_
;:y.
.
25 0 -t--_-p--
r-1
0
~--~~-
1
1995-1996 N=20
Fig 1.
ET AL
Table 3. Effect of Donor Age on Allograft Survival UNOS Data: October 1987 through December 1994
100
d
LACKNER, KOTHMANN
3 2 Years Post-Op
1990-1995 --
N = 97
Modification of immunosuppressive
1
-1--
4
5
18-34 y 35-49 y 50-64 y 65+y Current series 9-48 mo
84.00 80.00 76.00 71 .oo
74.00 68.00 62.00 53.00
63.00 57.00 49.00 40.00
75.00
63.00
54.00
1996-1989 N = 25
regimen.
allograft survival were done as Kaplan-Meier product limit estimates. Comparison between Kaplan-Meier curves was performed with the log-rank test. A P value < .05 was considered statistically significant. RESULTS
Actuarial patient survival for the entire series at 1,3, and 5 years was 91%, 85%, and 80%, respectively. Actuarial allograft survival for the entire series at 1,3, and 5 years was 74%, 59%, and 54%, respectively. Modifications in the immunosuppressive regimens for each of the three time intervals (1986 to 1989, 1990 to 1995, and 1995 to 1996) consistently improved allograft survival (Fig 1). In particular, the use of mycophenolate mofetil has eliminated allograft losses due to early rejection episodes. Of 20 patients receiving mycophenolate mofetil, none have had immunologic graft loss during the first 2 posttransplant months. Ultrasound determination of renal volume has demonstrated near doubling of volume within the first month posttransplant, with continued growth up to 1 year posttransplant as shown in Table 2. This increase in size has occurred with CyA and with FK 506 therapies. Renal function as measured by serum creatinine level is shown in Table 2. Serum creatinine showed continued improvement as renal volume increased. Surgical complications occurred in 20 of 142 (13.8%) patients. Renal artery thrombosis occurred in seven cases (5.8%) and was the only complication resulting in graft loss. Renal artery stenosis occurred in nine cases (6.2%) and was successfully managed by balloon angioplasty in six cases and open saphenous vein grafting in three cases. Renal arteryrelated complications occurred almost exclusively with kidneys from donors younger than 24 months of age (P I .Ol).
Urinary complications occurred in seven cases (5.8%) with six urine leaks and one obstruction, all of which were successfully repaired. None of the urine leaks were secondary to extensive ureteral necrosis. DISCUSSION
Allograft survival for adult cadaveric kidneys from donors aged 16 to 65+ years reported by UNOS is shown in Table 3.l Data on allograft survival for kidneys from donors younger than 5 years of age transplanted as en bloc pairs are shown in Table 4.6,7 Comparison of these data with the results reported here can provide answers as to whether pediatric donor kidneys should be recovered for transplantation and how can they be maximally utilized to benefit recipients. Results of transplants of single pediatric kidneys in our series are comparable to those of transplants from adult donors of an ideal age group and are equal or superior to those of transplants from older adult donors, especially when the most current immunosuppressive management is considered. In an evaluation of UNOS data on the impact of donor age on allograft survival, Alexander and Vaughn6 found that the worst outcome was in donors 12 to 24 months of age (1 year = 60%). In a previous report from our center, we found l-year allograft survival in this subset of patients to be 76% (n = 61),4 contradicting the prevailing opinion that single kidneys from donors in this age group cannot be safely transplanted into adult recipients.’ Surgical complications were reduced compared with other series, with allograft loss from technical reasons reduced to 5.8%. Urinary complications were reduced from 17.5% and 11% to 5.8%, all successfully managed.8,9 Single pediatric donor kidneys can be safely and effectively transplanted into adult recipients by patient selection, modification of surgical techniques to avoid vascular and urinary complications, and modification of immunosuppression to
Table 2. Renal Volume and Serum Creatinine
Postoperative Postoperative Postoperative Postoperative Postoperative
day day day day day
1 30 90 180 365
Mean Postoperative Renal Volume (ml)
Mean Postoperative Serum Creatinine (mg/dL)
51.9 98.9 119.7 162 163
9.3 2.7 2.2 2.0 1.6
Table 4. Allograft Survival in Adult Recipients of En Bloc Kidneys from Donors 5 Years or Younger Author
Nghiem’ Alexander and Vaughn’ Bretan et al’ Current series Kidneys 9-48 mo
i-y Allograft Survival (%)
72.00 60.00 88.00 (overall) 75.00 88.00% (mvcophenolate mofetil)
3273
PEDIATRIC DONORS
avoid early rejection episodes. Use of mycophenolate mofetil appears particularly beneficial in recipients of kidneys that are especially vulnerable to early rejection. Newer immunosuppressive agents may further improve results with pediatric donor kidneys. Transplantation as single organs rather than as en bloc pairs doubles the number of patients who can benefit from transplantation. Single transplantation may also provide better financial justification for organ recovery efforts since two renal acquisition charges are generated. En bloc transplantation does not appear to offer any advantages in terms of improved renal function, graft survival, or incidence of surgical complications.2~6~7 However, en bloc transplantation may have a role in the use of kidneys from donors younger than 12 months of age, and for use in larger recipients in circumstances such as O-mismatch or negative crossmatch in a sensitized individual. None of these options or benefits can be realized if kidneys are not recovered from young donors. It appears that in many areas of the country, these pediatric donors are not being identified and recovered, or they are recovered only for extrarenal organs. It has also been noted that kidneys have to be discarded because of transection of renal vessels or encroachment on the renal artery orifice by extrarenal teams who are not aware of the requirements for utilization of the kidneys. All of these factors should be addressed by the transplant community. The following conclusions from this study have been made: (I) Patient and allograft survival of adult recipients of single kidneys from donors 4 years or younger is acceptable; (2) the substitution of mycophenolate mofetil for
azathioprine virtually eliminated early graft loss to rejection and increased l-year actuarial allograft survival from 75% to 88%; (3) modifications in surgical techniques can reduce allograft loss from technical reasons to 5.8% and decrease ureteral complications from 17% and 11% to 5.8%; (4) single kidneys from the subset of donors 12 to 24 months of age can be safely transplanted into adult recipients; and (5) dramatic early growth of these kidneys can occur in patients receiving CyA or FK 506. The pediatric cadaveric organ donor is an underutilized resource and can represent an important contribution to the donor pool. It is up to the transplant community to make an effort similar to that made to expand the use of older donors. REFERENCES 1. United Network of Organ Sharing (UNOS): UNOS Data Base. Richmond, Va: UNOS, 1996 2. Bretan P, Friese C, Goldstein R, et al: Transplantation 63:233 3. Jacoby K, Lippman HR, Hura CE, et al: Clin Transplant 46:421, 1992 4. Banowsky LH, Wright FH, Kothmann R, et al: Transplant Proc 28:2121, 1996 5. Lippman H, Jacoby K, McFarlin L, et al: Clin Transplant 6:350, 1992 6. Alexander JW, Vaughn WK: Transplant Proc 51:135, 1991 7. Nghiem DD, Hsia S, Scholosser JD, et al: J Ural 153:326, 1995 8. Hayes JM, Novick AC, Steinmuller JR, et al: Transplant Proc 45:106, 1988 9. Satterwhite R, Aswad S, Sunga V, et al: Transplantation 63:1405, 1997
Results of Single Kidneys From Donors Aged 9 to 60 Months: Results in 144 Adult Recipients L.H. Banowsky,
J. Lackner,
R. Kothmann,
and F.H. Wright
T
HE INCREASING disparity between the number of potential recipients awaiting an organ transplant and the number of available cadaveric donor organs is the major problem in clinical transplantation today. Over 36,000 persons are currently awaiting kidney transplantation; while only 503.5 cadaveric donors were available in 1996. The renal waiting list has never decreased and has consistently grown larger each year. Liberalized acceptance criteria to include older donors, donors with medical conditions such as hypertension and diabetes, and donors with less than ideal renal function has resulted in some increase in organ recovery. The use of kidneys from donors over the age of 55 years has gained increased acceptance nationally and these donors have gone from 11% of the total in 1988 to 19% of the total for 1995.’ In contrast, the use of kidneys from pediatric donors younger than 5 years old has not increased and has not been promoted by the transplant community as an important source of cadaveric kidneys. United Network for Organ Sharing (UNOS) data have shown a decrease in pediatric donors from 330 (8.1% of total donors) in 1988 to 314 (5.9% of total donors) in 1995.’ From these donors, only 218 patients received renal transplants in 1988, indicating that 34% of the donors were not used and only 33% of the potential single-kidney utilization was achieved. This had marginally improved in 1995, with 231 patients receiving transplants, but still failing to use kidneys from some 24% of donors and reaching only 37% of the potential singlekidney utilization.’ This paper will report the San Antonio Community Hospital experience in transplanting single kidneys from donors younger than 4 years of age into adult recipients in 142 cases. Patient and allograft survival and renal function in these 142 transplants will be compared with UNOS data for transplants from donors 16 to 55 years of age, donors older than 55 years, and with reported en bloc transplants from donors younger than 5 years of age. A case will be made for increased recovery and utilization of kidneys from young donors. MATERIALS
AND
METHODS
From January 1986 through December 1996, 142 kidneys from cadaveric donors younger than 4 years of age were transplanted as single organs into adult recipients. Kidneys were allocated by
0 1997 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010 Transplantation
Proceedings,
29, 32713273
(1997)
Table 1. Donor and Recipient Characteristics Donor Characteristics Age: Mean = 23 mo 9-12 mo (n = 19) 13-24 mo (n = 74) 25-48 mo (n = 49) Weight: mean 27 lb (Q-51 lb) CMV Positive: 44% Preservation time: mean 37 h (18-52 h)
RecipientCharacteristics
Age: mean 41.2 y (16-66 y) Sex: 74 male and 68 female Weight: 136 lb (75-l 86 lb) Diabetes mellitus: 26% Previous transplant: 12% PRA: mean 12% (O-100%) 0 MM or 6-antigen: 7 (4.9%)
Abbreviations:CMV, cytomegalovirus,PRA, panel reactive antibody.
UNOS criteria with the stipulation that for medical reasons, recipient weight would be limited to approximately 160 lb. Unlike other series reported, no effort was made to exclude repeat transplants, sensitized patients, diabetics, or other potentially highrisk groups.’ Donor and recipient characteristics are shown in Table 1. The immunosuppressive regimens used from 1986 to 1989 and from 1990 to 1995 have been previously reported.3.4 In 1995, the regimen used from 1990 to 1995 was modified as follows: alternate patients received cyclosporine (CyA) or FK 506 and mycophenalate mofetil was used in all patients rather than azathioprine. Surgical technique has remained the same throughout the entire series and has been previously reported.5 Kidneys with single and multiple arteries were used as long as an aortic patch was available; failure of the donor surgeon to include a minimal aortic patch precluded use of the kidney. The venous anastomosis was done using an interrupted suture technique. Urinary reconstruction was by stented ureteroureterostomy or ureteropyeloneostomy. Patient follow-up included transplant renal ultrasound studies and calculation of renal volume on postoperative day 1 and at 1,3, 6, and 12 months. Serum creatinine and hematocrit levels were also obtained at these times. Allograft failure was defined as a return to chronic dialysis therapy or as any death with a functioning transplant. A patient death was considered as any death within 6 months of returning to chronic dialysis, or any death related to the transplant operation or immunosuppressive drugs. Calculation of actuarial patient and
From the Transplant Department, San Antonio Community Hospital, San Antonio, Texas, USA. Address reprint requests to Dr F.H. Wright, San Antonio Community Hospital, Transplant Dept, 8026 Floyd Curl Drive, San Antonio, TX 78229, USA.
0041-l 345/97/$17.00 PII so041 -1345(97)00907-X
3271
3272
BANOWSKY,
.‘..A 75 +
-.,.--
w
-
‘G
0” 50 B *
_
_-----
..‘.‘.........,
s
-7,
t-
--
Donor Age
---_
;:y.
.
25 0 -t--_-p--
r-1
0
~--~~-
1
1995-1996 N=20
Fig 1.
ET AL
Table 3. Effect of Donor Age on Allograft Survival UNOS Data: October 1987 through December 1994
100
d
LACKNER, KOTHMANN
3 2 Years Post-Op
1990-1995 --
N = 97
Modification of immunosuppressive
1
-1--
4
5
18-34 y 35-49 y 50-64 y 65+y Current series 9-48 mo
84.00 80.00 76.00 71 .oo
74.00 68.00 62.00 53.00
63.00 57.00 49.00 40.00
75.00
63.00
54.00
1996-1989 N = 25
regimen.
allograft survival were done as Kaplan-Meier product limit estimates. Comparison between Kaplan-Meier curves was performed with the log-rank test. A P value < .05 was considered statistically significant. RESULTS
Actuarial patient survival for the entire series at 1,3, and 5 years was 91%, 85%, and 80%, respectively. Actuarial allograft survival for the entire series at 1,3, and 5 years was 74%, 59%, and 54%, respectively. Modifications in the immunosuppressive regimens for each of the three time intervals (1986 to 1989, 1990 to 1995, and 1995 to 1996) consistently improved allograft survival (Fig 1). In particular, the use of mycophenolate mofetil has eliminated allograft losses due to early rejection episodes. Of 20 patients receiving mycophenolate mofetil, none have had immunologic graft loss during the first 2 posttransplant months. Ultrasound determination of renal volume has demonstrated near doubling of volume within the first month posttransplant, with continued growth up to 1 year posttransplant as shown in Table 2. This increase in size has occurred with CyA and with FK 506 therapies. Renal function as measured by serum creatinine level is shown in Table 2. Serum creatinine showed continued improvement as renal volume increased. Surgical complications occurred in 20 of 142 (13.8%) patients. Renal artery thrombosis occurred in seven cases (5.8%) and was the only complication resulting in graft loss. Renal artery stenosis occurred in nine cases (6.2%) and was successfully managed by balloon angioplasty in six cases and open saphenous vein grafting in three cases. Renal arteryrelated complications occurred almost exclusively with kidneys from donors younger than 24 months of age (P I .Ol).
Urinary complications occurred in seven cases (5.8%) with six urine leaks and one obstruction, all of which were successfully repaired. None of the urine leaks were secondary to extensive ureteral necrosis. DISCUSSION
Allograft survival for adult cadaveric kidneys from donors aged 16 to 65+ years reported by UNOS is shown in Table 3.l Data on allograft survival for kidneys from donors younger than 5 years of age transplanted as en bloc pairs are shown in Table 4.6,7 Comparison of these data with the results reported here can provide answers as to whether pediatric donor kidneys should be recovered for transplantation and how can they be maximally utilized to benefit recipients. Results of transplants of single pediatric kidneys in our series are comparable to those of transplants from adult donors of an ideal age group and are equal or superior to those of transplants from older adult donors, especially when the most current immunosuppressive management is considered. In an evaluation of UNOS data on the impact of donor age on allograft survival, Alexander and Vaughn6 found that the worst outcome was in donors 12 to 24 months of age (1 year = 60%). In a previous report from our center, we found l-year allograft survival in this subset of patients to be 76% (n = 61),4 contradicting the prevailing opinion that single kidneys from donors in this age group cannot be safely transplanted into adult recipients.’ Surgical complications were reduced compared with other series, with allograft loss from technical reasons reduced to 5.8%. Urinary complications were reduced from 17.5% and 11% to 5.8%, all successfully managed.8,9 Single pediatric donor kidneys can be safely and effectively transplanted into adult recipients by patient selection, modification of surgical techniques to avoid vascular and urinary complications, and modification of immunosuppression to
Table 2. Renal Volume and Serum Creatinine
Postoperative Postoperative Postoperative Postoperative Postoperative
day day day day day
1 30 90 180 365
Mean Postoperative Renal Volume (ml)
Mean Postoperative Serum Creatinine (mg/dL)
51.9 98.9 119.7 162 163
9.3 2.7 2.2 2.0 1.6
Table 4. Allograft Survival in Adult Recipients of En Bloc Kidneys from Donors 5 Years or Younger Author
Nghiem’ Alexander and Vaughn’ Bretan et al’ Current series Kidneys 9-48 mo
i-y Allograft Survival (%)
72.00 60.00 88.00 (overall) 75.00 88.00% (mvcophenolate mofetil)
3273
PEDIATRIC DONORS
avoid early rejection episodes. Use of mycophenolate mofetil appears particularly beneficial in recipients of kidneys that are especially vulnerable to early rejection. Newer immunosuppressive agents may further improve results with pediatric donor kidneys. Transplantation as single organs rather than as en bloc pairs doubles the number of patients who can benefit from transplantation. Single transplantation may also provide better financial justification for organ recovery efforts since two renal acquisition charges are generated. En bloc transplantation does not appear to offer any advantages in terms of improved renal function, graft survival, or incidence of surgical complications.2~6~7 However, en bloc transplantation may have a role in the use of kidneys from donors younger than 12 months of age, and for use in larger recipients in circumstances such as O-mismatch or negative crossmatch in a sensitized individual. None of these options or benefits can be realized if kidneys are not recovered from young donors. It appears that in many areas of the country, these pediatric donors are not being identified and recovered, or they are recovered only for extrarenal organs. It has also been noted that kidneys have to be discarded because of transection of renal vessels or encroachment on the renal artery orifice by extrarenal teams who are not aware of the requirements for utilization of the kidneys. All of these factors should be addressed by the transplant community. The following conclusions from this study have been made: (I) Patient and allograft survival of adult recipients of single kidneys from donors 4 years or younger is acceptable; (2) the substitution of mycophenolate mofetil for
azathioprine virtually eliminated early graft loss to rejection and increased l-year actuarial allograft survival from 75% to 88%; (3) modifications in surgical techniques can reduce allograft loss from technical reasons to 5.8% and decrease ureteral complications from 17% and 11% to 5.8%; (4) single kidneys from the subset of donors 12 to 24 months of age can be safely transplanted into adult recipients; and (5) dramatic early growth of these kidneys can occur in patients receiving CyA or FK 506. The pediatric cadaveric organ donor is an underutilized resource and can represent an important contribution to the donor pool. It is up to the transplant community to make an effort similar to that made to expand the use of older donors. REFERENCES 1. United Network of Organ Sharing (UNOS): UNOS Data Base. Richmond, Va: UNOS, 1996 2. Bretan P, Friese C, Goldstein R, et al: Transplantation 63:233 3. Jacoby K, Lippman HR, Hura CE, et al: Clin Transplant 46:421, 1992 4. Banowsky LH, Wright FH, Kothmann R, et al: Transplant Proc 28:2121, 1996 5. Lippman H, Jacoby K, McFarlin L, et al: Clin Transplant 6:350, 1992 6. Alexander JW, Vaughn WK: Transplant Proc 51:135, 1991 7. Nghiem DD, Hsia S, Scholosser JD, et al: J Ural 153:326, 1995 8. Hayes JM, Novick AC, Steinmuller JR, et al: Transplant Proc 45:106, 1988 9. Satterwhite R, Aswad S, Sunga V, et al: Transplantation 63:1405, 1997