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Transplantation of single and paired pediatric kidneys into adult recipients
Transplantation of Single and Paired Pediatric Kidneys into Adult Recipients Lloyd E. Ratner, MD, FACS, Francisco G. Cigarroa, MD, Jeffrey S. Bender, MD, FACS, Thomas Magnuson, MD, FACS, and Edward S. Kraus, MD Background: The transplantation of kidneys from cadaveric donors <---5 years of age into adult recipients is controversial. The large disparity between donor renal mass and recipient body mass is feared to be problematic. Controversy also exists whether to transplant kidneys from these young donors individually or as a pair into a single recipient.
a measure o f erythropoiesis were similar for single pediatric, paired pediatric, and adult-donor recipients.
Conclusions: Kidneys from cadaveric donors --< 5 years of age are suitable for transplantation into adults. Pediatric kidneys provide excellent renal function despite an initially tremendous disparity between renal mass and recipient body mass. Rapid true renal growth probably occurs. No appreciable advantage is achieved by using two pediatric kidneys for a single recipient. (J Am Coil Surg 1997;185:437-445. © 1997 by the American College of Surgeons)
Study Design: We retrospectively reviewed our experience from January 1991 to January 1995 with 22 adult renal transplantations using kidneys from cadaveric donors --< 5 years of age. Ten patients received single allografts. Twelve received organs paired en bloc. Fiftytwo adult recipients from cadaveric donors aged 1 8 - 5 5 years served as controls. All patients received cyclosporine-based immunosuppression. Recipient characteristics did not differ significantly between the groups.
T h e transplantation of kidneys from pediatric donors --< 5 years of age into adult recipients is controversial (1). The large disparity between d o n o r renal mass and recipient body mass is feared to be problematic. Hyperfiltration injury with resulting glomerular sclerosis is t h o u g h t to occur u n d e r these conditions (2-5). T h e small caliber of the d o n o r renal vessels and the d o n o r ureter also places these recipients at greater risk for technical complications. Many investigators have reported decreased graft survival when using these young d o n o r kidneys (6-10). Additional controversy exists whether to transplant kidneys from these y o u n g donors individually or as a pair en bloc into a single recipient (11). By providing double the functional renal mass, it is hypothesized that the paired en bloc pediatric kidneys will obviate the potentially deleterious effects of the d o n o r / r e c i p i e n t size disparity (11, 12). Additionally, because the vascular anastomoses are p e r f o r m e d using the d o n o r aorta and inferior vena cava, vessels of relatively large caliber, the risk of vascular thrombosis is believed to be diminished (10, 13, 14). Unfortunately, few comparative series of single versus double pediatric kidney transplants have b e e n published (8, 15, 16). The severe shortage of organs for transplantation has p r o m p t e d reevaluation of the issues associated with the transplantation of kidneys from young pediatric cadaveric donors. Optimal use of
Results: Actuarial patient and graft survival rates were similar for the two groups. The incidence o f urinary complications was higher in the recipients of pediatric kidneys than in the adult-donor group (18.2% versus 3.8%, respectively, p = not significant). N o grafts were lost from urinary complications. Renal function, as determined by the calculated creatinine clearance, was significantly greater in the pediatric group (76.1 -- 4.0 versus 61.4 - 23.2 mL/min, p = 0.035) by 6 months after transplantation. Recipients of paired pediatric kidneys initially had better renal function (63.9 -- 21.4 mL/min) than those receiving single pediatric kidneys (38.2 -+ 11.6 mL/min) (p = 0.004), but by 6 months, no significant difference existed. At 2 years, renal function in the pediatric-donor group remained significantly better than in the adult-donor group. Hematocrit levels as Received June 30, 1997; Accepted July 25, 1997. From the Departments of Surgery and Medicine, Johns Hopkins Bayview Medical Center, and Johns Hopkins University School of Medicine, Baltimore, MD, and Organ Transplantation Programs and Department of Pediatric Surgery, University of Texas Health Science Center, San Antonio, TX. Presented as a poster at the 14th Annual Meeting of the American Society of Transplant Physicians, Chicago, IL, May 1995. Correspondence address: Lloyd E. Ratner, MD, Department of Surgery, Johns Hopkins University School of Medicine, 600 N. Wolfe St., Harvey 611, Baltimore, MD 21287-8611. © 1997 by the American College of Surgeons Published by Elsevier Science Inc.
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ISSN 1072-7515/97/$17.00 PII S1072-7515(97)100-2
438 J AM COLL sugG
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these pediatric kidneys could provide additional organs for transplantation. The overall objective of this study was to determine whether kidneys from pediatric cadaveric donors aged -< 5 years are suitable for transplantation into adult recipients. Additional objectives were to d e t e r m i n e whether renal dysfunction secondary to hyperfiltration injury occurs in these patients a n d to d e t e r m i n e whether there is an advantage to transplanting these kidneys as a pair en bloc into a single recipient rather than as a single organ into two recipients. Me~o~
Patient and organ selection. A retrospective study was c o n d u c t e d of all patients who received kidneys from cadaveric organ donors aged -< 5 years at the Johns Hopkins Medical Institutions (Johns Hopkins Hospital and J o h n s Hopkins Bayview Medical Center) from January 1991 to January 1995. The control g r o u p consisted of the recipients of 52 consecutive cadaveric transplants p e r f o r m e d at the J o h n s Hopkins Bayview Medical Center over the same time period using organs from adult donors aged 18-55 years. Pediatric kidneys were transplanted either as a single organ or as a pair en bloc d e p e n d i n g on whether the procuring surgeon h a d separated t h e m at the time of organ harvest. The decision to separate the kidneys was m a d e i n d e p e n d e n t of any input from the transplanting surgeon. In no instance did the procuring surgeon also p e r f o r m the transplantation for the pediatric-donor group. Operative technique. Kidneys from adult donors and single pediatric kidneys were transplanted in the standard fashion. Vascular anastomoses for all single pediatric kidneys used an aortic Carrel patch for the arterial anastomosis and a cuff of vena cava for the venous anastomosis. Paired pediatric kidneys were left en bloc on the aorta and inferior vena cava. T h e d o n o r proximal aorta and proximal inferior vena cava were oversewn with 7-0 polypropylene suture. The distal d o n o r aorta and inferior vena cava were anastomosed to the recipient iliac vessels in an end-to-side fashion. En bloc paired kidneys were positioned in the right iliac fossa with the d o n o r left kidney in the medial position. Ureteral anastomoses were p e r f o r m e d using a modification of the extravesicle ureteroneocystostomy described by Lich and associates (17). The one exception to this was in a patient who received a pair of en bloc pediatric kidneys with three ureters. In that patient, the ureteral a n a s t o m o s e s were accomplished using the
Politano-Leadbetter technique (18). Ureteral stents were n o t used routinely, b u t if there was concern about the ureteral vascular supply, a 6F, 16-cm double-J stent was left in place for 4 - 6 weeks. No attempt was made to pexy the kidneys in position in the retroperitoneum, and the peritoneal sack was n o t o p e n e d intentionally. Posttransplantation management. Most recipients of pediatric d o n o r kidneys were m a i n t a i n e d on intravenous heparin t h r o u g h o u t their postoperative hospitalization. The heparin dose was adj u s t e d to maintain an activated partial thromboplastin time of 1.3-1.5 times control. All recipients received cyclosporine-based i m m u n o s u p p r e s s i o n therapy a n d were cared for by the same physicians. Those patients with p o o r renal function in the early postoperative period received quadruple sequential i m m u n o s u p p r e s s i o n using either ATGAM (Upjohn, Kalamazoo, MI) or OKT3 (Ortho Biotech Inc., Raritan, NJ) before c o m m e n c i n g cyclosporine therapy. Calculation of creatinine clearance. Recipient creatinine clearance was calculated using the Cockroft-Gault formula (19) : [140 - age (y)] [weight (kg)]* 72 [serum creatinine ( m g / d L ) ] * (females × 0.85).
Statistical analysis. Statistical analysis was perf o r m e d using SigmaStat (Jandel Inc., San Rafael, CA) and Statgraphics Plus 6.1 (Manugistics, Rockville, MD) statistical software packages. Differences between groups were calculated using the Student's t-test for parametric data and the MannWhitney rank-sum test for nonparametric data. Survival curves were d e t e r m i n e d using the KaplanMeier m e t h o d (20). Those patients who died with a functioning allograft were considered as a graft loss. Differences in survival between groups were d e t e r m i n e d using the log-rank test. Values of p < 0.05 were considered significant. Results
Recipient characteristics. The recipients in the pediatric- and adult-donor groups did n o t differ in regard to age, weight, gender, race, n u m b e r of patients with high panel reactive antibody, number of patients who had previous transplantations, or n u m b e r of diabetic recipients (Table 1). Eleven recipients (50%) of pediatric kidneys received quadruple sequential immunosuppression, as did 34 recipients (65%) in the adult-donor group (p = n o t significant).
Ratner Table 1. R e c i p i e n t Characteristics* Characteristic
Pediatric
Number Age (y) Weight (kg) Male Female Black White eRA > 10% Previous Tx Diabetes
Adult
22 45.2 ± 12.7 81.3 ± 23.7 15 (68.2%) 7 (31.8%) 13 (59.1%) 9 (40.9%) 1 (4.5%) 0 2 (9.1%)
52 44.6 + 11.7 75.4 -+ 17.2 31 (59.6%) 21 (40.4%) 26 (50.0%) 26 (50.0%) 1 (1.9%) 8 (15.4%) 13 (25.0%)
*There were no significant differences between the groups. PRA, panel reactive antibody; Tx, transplantation.
Pediatric-donor characteristics. Twenty-two patients received kidneys f r o m pediatric cadaveric organ d o n o r s aged -< 5 years. Ten o f these recipients received a single pediatric kidney a n d 12 received p a i r e d en bloc pediatric kidneys. Overall, the donors o f the kidneys transplanted as a pair en bloc t e n d e d to be y o u n g e r a n d smaller than the donors
e t al
TRANSPLANTATION OF PEDIATRIC KIDNEYS 4 3 9
of the kidneys transplanted as a single organ into a single recipient, but these differences in d o n o r age and size were not statistically significant (Table 2). Ischemic time and acute tubular necrosis. Cold ischemic time for the pediatric-donor group (29.30 -_ 8.25 hours) was significantly l o n g e r than that for the control group (23.88 _+ 11.53 hours) (p = 0.037). W h e n the pediatric group was stratified b e t w e e n recipients o f single a n d paired e n bloc kidneys, no difference in ischemic time was observed (Table 2). T h e incidence o f acute tubular necrosis (defined as the n e e d for dialysis d u r i n g the first week after transplantation) was 30.8% for the control group and 23.8% for the pediatric-donor c o h o r t (p = n o t significant). Patient and graft survival. T h e r e was no differe n c e in patient survival between the pediatricd o n o r a n d adult-donor groups. At 3 years, patient survival was 85.0% a n d 85.9% for the recipients o f
Table 2. C o m p a r i s o n o f P a t i e n t Characteristics a n d O u t c o m e s in t h e Two Groups*
Patient
Recipient race/ gender
Recipient weight (kg)
Donor race/ gender
Donor weight (kg)
Donor age (mo)
Cold ischemic time (h)
Acute tubular necrosis
Complication
Paired en bloc kidneys D.B.
W/F
45
W/F
20
45
35.35
No
W.C. J.C.
W/M B/M
95 78
W/M B/F
16 10.5
30 21
45.12 19.12
No Yes
D.F.
W/F
81
W/M
11
24
28.95
R.F. R.G. R.L. E.M. O.R. T.S.
B/M B/F B/M B/F W/F B/M
50 99 93 74 96 109
W/M W/F W/M W/M W/F W/F
14 15 17 12 15 12
36 36 42 33 47 36
23.00 33.47 26.78 30.83 39.75 27.57
No No No No No No
E.W.
B/M
79
B/M
8
26
18.60
Yes
E.W.
W/M 5W, 7B, 5F, 7M
94 82.8 ± 26.8
W/F 10W, 2B, 6F, 6M
20 14.2 -+ 3.7
52 35.7 -+ 9.6
22.92 29.0 + 7.6
No 18.2%
C.B. JJ. M.M. M.M.
W/M B/M B/F B/M
127 64 53 72
W/M W/M B/F B/F
16 20 32 20
51 69 61 38
28.75 35.95 8.30 26.32
No No No Yes
J.M. W.P. J.P. T.R. A.S.
B/M W/M B/M W/M B/F
112 79 70 69 54
B/F W/M W/F W/F W/F
11 18 16 12 20
24 70 30 31 71
42.63 25.38 38.48 28.17 28.85
Yes No No No No
B.S.
W/M 4W, 6B, 2F, 8M
116 81.6 -+ 26.8
W/F 8W, 2B, 7F, 3M
33.37 29.6 + 9.4
Yes 30.0
Mean
Acute rejection---~ graft thrombosis Cardiovascular death Hypotension--~graft thrombosis Ureteral stricture
Bladder leak (three ureters) Ureteral necrosis; late infectious death
Single pediatric kidneys
Mean
12 31 17.7 ± 6.1 47.6 ± 18.9
Focal segmental glomerulosclerosis
Ureteral necrosis; late infectious death
*The donors tended to be smaller and younger in the paired pediatric kidney group than in the single pediatric kidney group, but no statisticaldifference was observed for either weight or age. W, white; F, female; M, male; B, black.
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100 90 80 70 60
............Pediatric D o n o r (n=22) A d u l t D o n o r (n=52)
50 40 30
-
20 10 0
I
0
I
1
I
2
p=NS
I
3
I
4
5
Years
FIG 1. Patient survival was similar for recipients for pediatric-donor (age --< 5 years) and adult-donor (age 18-55 years) kidneys (log-rank test, p = not significant).
pediatric-donor and adult-donor kidneys, respectively (Fig. 1). Similarly, no differences were observed in graft survival between the adult- and pediatric-donor groups. At 3 years, the calculated allograft survival was 76.4% for the recipients of pediatric-donor kidneys and 69.9% for the recipients of kidneys from donors aged 18-55 years (p = not significant) (Fig. 2). All causes of graft failure and patient death are listed in Table 3. The leading cause of graft loss in both the pediatric- and adult-donor groups was
death with a functioning allograft. Technical complications were an unusual cause of graft loss. Graft thrombosis occurred in one recipient of a paired en bloc pediatric allograft when the patient became hypotensive in the immediate postoperative period. One adult kidney had a renal artery thrombosis, presumably for technical reasons. No graft thrombosis was observed in the recipients of single pediatric kidneys. Urinary complications. Four recipients (18.2 % ) of pediatric k i d n e y s had urinary complications.
100 90 80 70 60
m
.........Pediatric D o n o r (n=22) - A d u l t D o n o r (n=52)
50 40 30 20
m
10 0
I
0 p=NS
I
1
I
2
I
3
I
4
5
Years
FIG 2. Graft survival was comparable for recipients for pediatric-donor (age --< 5 years) and adult-donor (age 18-55 years) kidneys (log-rank test, p = not significant).
R a t n e r et al Table 3. Causes of Graft Loss* Pediatric Cause
no
Death Graft thrombosis Acute rejection C h r o n i c rejection Primary n o n f u n c t i o n R e c u r r e n t disease *There
were no significant
no
13.6 4.5 4.5
differences
function, as d e t e r m i n e d by the calculated creatin i n e clearance. By 6 m o n t h s after transplantation, the recipients in the pediatric-donor group h a d significantly greater creatinine clearances than recipients in the adult-donor group: 76.1 -+ 24.0 versus 61.4 -+ 23.2 m L / m i n , respectively (p = 0.035) (Fig. 3). At 1 year after transplantation, creatinine clearance rates were 89.1 _+ 33.6 a n d 63.0 _+ 27.8 m L / m i n for the --< 5-year d o n o r group a n d the 1 8 - 5 5 - y e a r d o n o r group, respectively (p = 0.008). Similarly, at 2 years postoperatively, the creatinine clearances were 107.8 _+ 25.3 and 60.0 _+ 23.4 m L / m i n for the pediatric- and adult-donor groups, respectively (p < 0.001). Recipients of paired pediatric kidneys initially had better renal function (63.9 +- 21.4 m L / m i n ) than recipients of single pediatric kidneys (38.2 - 11.6 m L / m i n ) (p = 0.004), but by 6 months, no significant difference existed (Fig. 4). Hematocrit levels as a measure of erythropoiesis were similar for single pediatric, paired pediatric, and adult-donor recipients (Fig. 5). Proteinuria d e v e l o p e d after transplantation in f o u r recipients o f pediatric kidneys. In two patients, the p r o t e i n u r i a resolved spontaneously a n d so it was p r e s u m e d to be o f native kidney origin. Proteinuria abated in one recipient after an angiotensin-converting enzyme inhibitor was a d d e d to his antihypertensive regimen. Renal allograft biopsy d e m o n s t r a t e d focal segmental glomerulosclerosis in the final patient with proteinuria, but that patient continues to have g o o d renal function a n d is d o i n g well without dialysis.
Adult %
3 1 1 0 0 0
between
%
6 1 1 1 1 1
TRANSPLANTATIONOF PEDIATRIC KIDNEYS 441
11.5 1.9 1.9 1.9 1.9 1.9
the groups.
T h r e e of these patients had received paired e n bloc kidneys a n d one received a single pediatric kidney. T h e urinary complications in the paired en bloc group consisted of o n e ureteral stricture, o n e ureteral necrosis secondary to an invasive Candida infection, a n d one leak f r o m the anterior cystotomy in the patient who h a d a Po!itanoL e a d b e t t e r u r e t e r o n e o c y s t o s t o m y (18). The o n e urinary complication in a recipient o f a single pediatric kidney consisted o f a necrotic u r e t e r s e c o n d a r y to an invasive enterococcal infection. In the g r o u p that received allografts f r o m adult donors, ureteral distal tip necrosis developed in two patients (3.8%). In all cases, ureteral necrosis was treated p r o m p t l y by resection o f the allograft ureter, a n d a ureteropyelostomy was p e r f o r m e d using the ipsilateral native ureter. T h e one patient with a ureteral stricture h a d this c o r r e c t e d by percutaneous stenting. No grafts were lost f r o m urinary complications. Renal allograft function. Kidneys p r o c u r e d f r o m d o n o r s - 5 years o f age provided excellent renal 200 175
Pediatric
/x Adult
©
o 150 t'-
I I I..--'----.
o 125 ~D 0 CD c"
"~
[
IO0 75 5O
(D
25 0 *p=NS all others p
t
I [
1
i
i
i
i
i
i
, i
i
D
0.5
1.0
1.5
2.0
2.5
3.0
3.5
]-[me P o s t - T r a n s p l a n t (Years)
FIG 3. Comparison of pediatric- and adult-donor recipient calculated creatinine clearances (mL/min) over time. At the time of discharge, mean creatinine clearance was comparable between the groups, but by 6 months after transplantation, allograft renal function was significantly better in the pediatric-donor cohort.
442 J AM COLL SURe N O W M B E R 1997
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180 160
c~ 140 120 100 "E
~-~ Single
lPQired
[
T
l
80 60
(.3
40 20 0
*p=O.O04
e~
%
all others p=NS FIG 4. Calculated recipient creatinine clearance of the single-kidney pediatric-donor group versus the paired en bloc kidney pediatric-donor group. At the time of discharge, the paired kidneys provided approximately double the renal function of the single kidneys, but by 6 months after transplantation, there was no observable significant difference.
Discussion
The transplantation literature is replete with series from individual institutions a n d registry data that report p o o r e r results when kidneys from young pediatric donors are used (3, 5-10). Yet many authors have r e p o r t e d g o o d results when these kidneys are transplanted (14, 16, 21-23). There continues to be reluctance by many centers to transplant kidneys from donors aged -< 5 years into adult recipients. O n e major concern is the large disparity between d o n o r renal mass a n d recipient body mass. It has b e e n hypothesized that this large discrepancy between renal mass and body mass results in glomerular sclerosis secondary to hyperfiltration injury (2). There have been reports of focal segmental glomerulosclerosis developing in pediatric kidneys that were transplanted into adults (4, 5, 24, 25). In contrast, our experience indicates that the d e v e l o p m e n t of focal segmental glomerulosclerosis m pediatricd o n o r kidneys (4.5%) is probably an unusual occurrence. In addition, the judicious use of angiotensin-converting enzyme inhibitors in patients with systemic hypertension or proteinuria may be beneficial in preventing hyperfiltration lesions (26, 27). In any event, the progressive decline in renal function that would be predicted in the case of glomerular hyperfiltration injury was n o t observed. In our series, renal function c o n t i n u e d t o improve with time, and at 1 year after transplanta-
tion, the m e a n pediatric-kidney recipient creatinine clearance was greater than that obtained in the adult-donor group: 89.1 _+ 33.6 versus 63.0 + 27.8 m L / m i n , respectively (p = 0.008) (Fig. 4). Similar results were reported by N g h i e m and colleagues (12) for pediatric kidneys transplanted en bloc into adult recipients. In that study, the m e a n glomerular filtration rate increased from 22.5 + 14.2 to 85.3 +_ 52.3 m L / m i n by 6 m o n t h s a n d to 120.7 -+ 45.1 m L / m i n after 6 months. In the same series, renal allograft volume was n o t e d to have increased nearly threefold within 6 months. An incremental i m p r o v e m e n t in renal function was observed in both the single and paired en bloc pediatric cohorts in our series. Single pediatric kidneys initially provided approximately half the renal function of the en bloc paired kidneys, but rapidly achieved a similar level of function and c o n t i n u e d to perform well longterm. Primary n o n f u n c t i o n a n d acute rejection have been reported as problems in pediatric-donor kidneys (8, 10). This may reflect older series compiled before the introduction of current organpreservation techniques. An increased incidence of primary n o n f u n c t i o n was n o t observed in our patients. Alternatively, primary n o n f u n c t i o n may reflect severe acute rejection in the face of acute tubular necrosis. Indeed, rejection has been cited as the leading cause of graft loss for pediatricd o n o r kidneys (7, 10, 12, 15, 28). We used aggressive immunosuppressive therapy in the early post-
Ratner et al
TRANSPLANTATIONOF PEDIATRICKIDNEYS 443
55 50 45
•
Srngle Ped[Qtr[c
55
.
[
| /
- - - - - -
r
T
_..m ' ' m ' - n
.//Y--Y/Y
•c 40 o o
T
V Pc[red En Bloc
T
E 50 25 20 I
%
%
%
%
%
,--
FIG 5. Recipient hematocrit levels as an indication of erythropoiesis were not different between the single and paired pediatric renal allografts. No significant difference in posttransplant hematocrit was observed between the pediatric-donor group and the adult-donor group (data not shown).
transplant period because pediatric kidneys may n o t tolerate a serious rejection episode as well as adult kidneys. An illustration of this was the one patient in our series who lost her allograft from acute cellular rejection. In that case, the allograft u n d e r w e n t thrombosis during an acute rejection episode > 1 m o n t h after transplantation, possibly because of increased resistance in small pediatric vessels. Allograft thrombosis and renovascular complications were n o t m a j o r problems in o u r series. O t h e r groups have reported an increased incidence of both allograft thrombosis (5) a n d renal artery stenosis (7, 10, 13). Like other investigators, we call attention to the importance of meticulous technical detail (13, 23, 29). For paired en bloc organs, a variety of techniques have been proposed to prevent torsion of the kidney on its vascular pedicle. These techniques have included fixi n g the allograft in Vicryl mesh (Ethicon, Somerville, NJ) (30), pexying the medial kidney to the bladder (13), and intraperitonealizing the medial kidney (23). We have n o t used these modifications and have n o t yet f o u n d torsion of the kidney to be a problem. Urinary complications have been n o t e d to be a p r o b l e m with these small kidneys (4, 5, 10, 13). In our series, 4 of 22 recipients (18.2%) of pediatric kidneys experienced urinary complications, but no grafts were lost after p r o m p t and aggressive m a n a g e m e n t . Hayes and coworkers (31) advocated the routine use of ureteral stents for renal
allografts p r o c u r e d from donors < 6 years of age. O u r experience indicates that this r e c o m m e n d a tion is prudent. O n the basis of this review, we have altered our practice to include the routine use of ureteral stents in pediatric-donor kidneys. The extreme shortage of organs for transplantation requires that use of these pediatric kidneys be optimized. The previous c o m p a r i s o n by Gruessner and colleagues (15) of single versus paired pediatric kidneys showed better graft survival in paired en bloc kidneys, but overall m o r e patients r e m a i n e d off dialysis with functioning kidneys if they received a single kidney. Other series have d e m o n s t r a t e d acceptable results with single pediatric kidneys (8, 10, 21, 22, 32, 33). The use of paired pediatric kidneys has r e m a i n e d theoretically attractive because of the concern about hyperfiltration injury. Yet pediatric kidneys have been d e m o n s t r a t e d to grow rapidly when transplanted into adults (12, 14). O u r data indicate that a good "low mileage" pediatric kidney may provide even better function than an adult kidney if allowed to grow without early insults such as acute rejection. Because comparable results can be obtained with single versus en bloc pediatric kidneys, there is little justification for using en bloc kidneys. O n e caveat is that in the present series, we did n o t randomize the en bloc and single pediatric donors. In general, the en bloc donors were slightly younger and smaller than the donors of kidneys transplanted individually (Table 2). Several reports have d e m o n s t r a t e d good results with
444 J AM COLL SURG NOVEMBER1997
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kidneys from children 3-5 years of age, but p o o r e r results with kidneys from donors -< 3 years o l d (6, 8-10). We would be cautious when using individual kidneys from very small donors. With the growing disparity between organ supply and d e m a n d , kidneys from donors > 60 years of age have been transplanted with increasing frequency and a c c o u n t e d for 6% of cadaveric renal transplantations in the United States in 1993, as o p p o s e d to 2% in 1988 (34). W h e n viewed from this perspective, pediatric d o n o r kidneys yield better results than those obtained with organs from older donors. United Network for Organ Sharing registry data have reported renal allograft halflives of 8.8 years a n d 5.0 years for donors --< 5 years and > 60 years of age, respectively (p < 0.001) (34). In fact, U n i t e d Network for Organ Sharing registry data indicated that the allograft half-life for organs from donors aged --- 5 years compares favorably with that obtained with donors aged 4 6 - 6 0 years, and is comparable to that resulting from transplanting cadaveric kidneys from adult donors 31-45 years of age (34). In summary, the transplantation of kidneys from young pediatric donors -< 5 years of age can result in both patient and allograft survival that is comparable to that achieved with organs p r o c u r e d from adult cadaveric donors. Allograft functional adaptation occurs rapidly for both single and paired pediatric kidneys when transplanted into adult recipients. In fact, pediatric d o n o r kidneys provide better recipient creatinine clearance than do adult-donor renal allografts. Ureteral complications were m o r e frequent in the pediatric-donor group but did n o t negatively affect graft survival. We conclude that kidneys from pediatric donors -< 5 years of age are suitable for transplantation into adults and should be used when available. There appears to be no advantage to transplanting these young d o n o r kidneys as a pair en bloc. To make optimal use of these kidneys, this practice should be discouraged and individual pediatric kidneys should be used for individual recipients. References 1. Fine RN. Renal transplantation of the infant and young child and the use of pediatric cadaver kidneys for transplantation in pediatric and adult recipients. Am J Kidney Dis 1988;12: 1-10. 2. Brenner BM, Cohen RA, and Milford EL. In renal transplantation, one size may not fit all.j Am Soc Nephrol 1992;3:162169. 3. Terasaki PI, Koyama H, Cecka JM, and Gjertson DW. The hyperfiltration hypothesis in human renal transplantation. Transplantation 1994;57:1450-1454. 4. Hayes JM, Steinmuller DR, Streem SB, and Novick AC. The
5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28.
development of proteinuria and focal-segmental glomerulosclerosis in recipients of pediatric donor kidneys. Transplantation 1991;52:813-817. Neumayer HH, Huls 8, Schreiber M, et al. Kidneys from pediatric donors: risk versus benefit. Clin Nephrol 1994;41: 94-100. Creagh TA, McLean PA, Spencer S, et al. Transplantation of kidneys from pediatric cadaver donors to adult recipients. J Urol 1991;146:951-952. Gourlay W, Stothers L, McLoughlin MG, et al. Transplantation of pediatric cadaver kidneys into adult recipients. J Urol 1995;153:322-325. Ildstad ST, Tollerud DJ, NoseworthyJ, et al. The influence of donor age on graft survival in renal transplantation.J Pediau Surg 1990;25:134-139. Ruder H, Schaefer F, Gretz N, et al. Donor kidneys of infants and very young children are unacceptable for transplantation. Lancet 1989;2:168. Wengerter K, Tellis V, Soberman R, et al. Transplantation of pediatric donor kidneys to adult recipients: is there a critical donor age? Ann Surg 1986;204:172-175. Schneider JR, Sutherland DER, Simmons RL, et al. Longterm success with double pediatric cadaver donor renal transplants. Ann Surg 1983;197:439-442. Nghiem DD, Hsia S, and SchlosserJD. Growth and function of en bloc infant kidney transplants: a preliminary study. J Urol 1995;153:326-329. Merkel FK, Matalon TAS, Bru.nner MC, et al. Short- and long-term results with en bloc transplantation of pediatric kidneys into adults. Transplant Proc 1993;25:2167-2169. Ratner LE, and Flye MW. Transplantation of en-bloc pediatric kidneys into adult recipients. Transplantation 1991;51: 273-274. Gruessner RWG, Matas AJ, Lloveras G, et al. A comparison of single and double pediatric cadaver donor kidneys for transplantation. Clin Transplant 1989;3:209-214. van der Vliet JA, Cohen B, and Kootstra G. Transplantation of pediatric cadaver kidneys. Transplant Proc 1982;14:74-76. Lich R, Howerton LW, and Davis LA. Recurrent urosepsis in children. J Urol 1961;86:554-558. Weil R, Simmons RL, Tallent MB, et al. Prevention of urological complications after kidney transplantation. Ann Surg 1971;174:155. Cockroft DW, and Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976;16:31-41. Kaplan EL, and Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958;53:457. Abouna GM, Kumar MSA, Brezin J, et al. Transplantation of single pediatric cadaveric kidneys into adult recipients. Transplant Proc 1993;25:2170-2171. Boczko S, Tellis V, and Veith F. Transplantation of children's kidneys into adult recipients. Surg Gynecol Obstet 1978;146: 387-390. Nghiem DD. En bloc transplantation of kidneys from donors weighing less than 15 kg into adult recipients. J Urol 1991; 145:14-16. Woolley AC, Rosenberg ME, Burke BA, and Nath KA. De novo focal glomerulosclerosis after kidney transplantation. AmJ Med 1988;8~4:310-314. Leunissen KML, Kootstra G, Bosman FT, and van HooffJP. Focal glomerulosclerosis in neonatal kidney grafts. Lancet 1987;2:1019-1020. Heeg JE, de Jong PE, van der Hem GK, and de Zeeuw D. Reduction of proteinuria by angiotensin converting enzyme inhibition. Kidney Int 1987;32:78-83. Anderson S, Meyer TW, Rennke HG, and Brenner BM. Control of glomerular hypertension limits glomerular injury in rats with reduced renal mass. J Clin Invest 1985;76:612=619. Smith AY, van Buren CT, Lewis RM, et al. Short-term and long-term function of cadaveric kidneys from pediatric donors in recipients treated with cyclosporlne. Transplantation 1988;45:360-367.
Ratner
29. HayesJM. The transplantation of difficult donor kidneys and recipients: helpful surgical techniques. J Urol 1993;149:250254. 30. Lowell JA, Cattral MS, Freel MS, et al. Use of a Vicryl mesh envelope to prevent vascular occlusion of pediatric donor kidney transplants. Transplant Proc 1994;26:39-41. 31. Hayes JM, Novick AC, Streem SB, et al. The use of single pediatric cadaver kidneys for transplantation. Transplantation 1988;45:106-110.
e t al
TRANSPLANTATION OF PEDIATRIC KIDNEYS 4 4 5
32. Glass NR, Stillman RM, Butt KMH, and Kountz SL. Results of renal transplantation using pediatric cadaver donors. Surgery 1979;85:504-508. 33. Kootstra G, West JC, Dryburgh P, et al. Pediatric cadaver kidneys for transplantation. Surget3~ 1978;83:333-337. 34. CeckaJM, and Terasaki PI. The UNOS scientific renal transplant registry. In: CeckaJM, Terasaki PI, eds. Clinical Transplants 1994. Los Angeles: UCLA Tissue Typing Laboratory; 1995:1-18.
a measure o f erythropoiesis were similar for single pediatric, paired pediatric, and adult-donor recipients.
Conclusions: Kidneys from cadaveric donors --< 5 years of age are suitable for transplantation into adults. Pediatric kidneys provide excellent renal function despite an initially tremendous disparity between renal mass and recipient body mass. Rapid true renal growth probably occurs. No appreciable advantage is achieved by using two pediatric kidneys for a single recipient. (J Am Coil Surg 1997;185:437-445. © 1997 by the American College of Surgeons)
Study Design: We retrospectively reviewed our experience from January 1991 to January 1995 with 22 adult renal transplantations using kidneys from cadaveric donors --< 5 years of age. Ten patients received single allografts. Twelve received organs paired en bloc. Fiftytwo adult recipients from cadaveric donors aged 1 8 - 5 5 years served as controls. All patients received cyclosporine-based immunosuppression. Recipient characteristics did not differ significantly between the groups.
T h e transplantation of kidneys from pediatric donors --< 5 years of age into adult recipients is controversial (1). The large disparity between d o n o r renal mass and recipient body mass is feared to be problematic. Hyperfiltration injury with resulting glomerular sclerosis is t h o u g h t to occur u n d e r these conditions (2-5). T h e small caliber of the d o n o r renal vessels and the d o n o r ureter also places these recipients at greater risk for technical complications. Many investigators have reported decreased graft survival when using these young d o n o r kidneys (6-10). Additional controversy exists whether to transplant kidneys from these y o u n g donors individually or as a pair en bloc into a single recipient (11). By providing double the functional renal mass, it is hypothesized that the paired en bloc pediatric kidneys will obviate the potentially deleterious effects of the d o n o r / r e c i p i e n t size disparity (11, 12). Additionally, because the vascular anastomoses are p e r f o r m e d using the d o n o r aorta and inferior vena cava, vessels of relatively large caliber, the risk of vascular thrombosis is believed to be diminished (10, 13, 14). Unfortunately, few comparative series of single versus double pediatric kidney transplants have b e e n published (8, 15, 16). The severe shortage of organs for transplantation has p r o m p t e d reevaluation of the issues associated with the transplantation of kidneys from young pediatric cadaveric donors. Optimal use of
Results: Actuarial patient and graft survival rates were similar for the two groups. The incidence o f urinary complications was higher in the recipients of pediatric kidneys than in the adult-donor group (18.2% versus 3.8%, respectively, p = not significant). N o grafts were lost from urinary complications. Renal function, as determined by the calculated creatinine clearance, was significantly greater in the pediatric group (76.1 -- 4.0 versus 61.4 - 23.2 mL/min, p = 0.035) by 6 months after transplantation. Recipients of paired pediatric kidneys initially had better renal function (63.9 -- 21.4 mL/min) than those receiving single pediatric kidneys (38.2 -+ 11.6 mL/min) (p = 0.004), but by 6 months, no significant difference existed. At 2 years, renal function in the pediatric-donor group remained significantly better than in the adult-donor group. Hematocrit levels as Received June 30, 1997; Accepted July 25, 1997. From the Departments of Surgery and Medicine, Johns Hopkins Bayview Medical Center, and Johns Hopkins University School of Medicine, Baltimore, MD, and Organ Transplantation Programs and Department of Pediatric Surgery, University of Texas Health Science Center, San Antonio, TX. Presented as a poster at the 14th Annual Meeting of the American Society of Transplant Physicians, Chicago, IL, May 1995. Correspondence address: Lloyd E. Ratner, MD, Department of Surgery, Johns Hopkins University School of Medicine, 600 N. Wolfe St., Harvey 611, Baltimore, MD 21287-8611. © 1997 by the American College of Surgeons Published by Elsevier Science Inc.
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ISSN 1072-7515/97/$17.00 PII S1072-7515(97)100-2
438 J AM COLL sugG
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these pediatric kidneys could provide additional organs for transplantation. The overall objective of this study was to determine whether kidneys from pediatric cadaveric donors aged -< 5 years are suitable for transplantation into adult recipients. Additional objectives were to d e t e r m i n e whether renal dysfunction secondary to hyperfiltration injury occurs in these patients a n d to d e t e r m i n e whether there is an advantage to transplanting these kidneys as a pair en bloc into a single recipient rather than as a single organ into two recipients. Me~o~
Patient and organ selection. A retrospective study was c o n d u c t e d of all patients who received kidneys from cadaveric organ donors aged -< 5 years at the Johns Hopkins Medical Institutions (Johns Hopkins Hospital and J o h n s Hopkins Bayview Medical Center) from January 1991 to January 1995. The control g r o u p consisted of the recipients of 52 consecutive cadaveric transplants p e r f o r m e d at the J o h n s Hopkins Bayview Medical Center over the same time period using organs from adult donors aged 18-55 years. Pediatric kidneys were transplanted either as a single organ or as a pair en bloc d e p e n d i n g on whether the procuring surgeon h a d separated t h e m at the time of organ harvest. The decision to separate the kidneys was m a d e i n d e p e n d e n t of any input from the transplanting surgeon. In no instance did the procuring surgeon also p e r f o r m the transplantation for the pediatric-donor group. Operative technique. Kidneys from adult donors and single pediatric kidneys were transplanted in the standard fashion. Vascular anastomoses for all single pediatric kidneys used an aortic Carrel patch for the arterial anastomosis and a cuff of vena cava for the venous anastomosis. Paired pediatric kidneys were left en bloc on the aorta and inferior vena cava. T h e d o n o r proximal aorta and proximal inferior vena cava were oversewn with 7-0 polypropylene suture. The distal d o n o r aorta and inferior vena cava were anastomosed to the recipient iliac vessels in an end-to-side fashion. En bloc paired kidneys were positioned in the right iliac fossa with the d o n o r left kidney in the medial position. Ureteral anastomoses were p e r f o r m e d using a modification of the extravesicle ureteroneocystostomy described by Lich and associates (17). The one exception to this was in a patient who received a pair of en bloc pediatric kidneys with three ureters. In that patient, the ureteral a n a s t o m o s e s were accomplished using the
Politano-Leadbetter technique (18). Ureteral stents were n o t used routinely, b u t if there was concern about the ureteral vascular supply, a 6F, 16-cm double-J stent was left in place for 4 - 6 weeks. No attempt was made to pexy the kidneys in position in the retroperitoneum, and the peritoneal sack was n o t o p e n e d intentionally. Posttransplantation management. Most recipients of pediatric d o n o r kidneys were m a i n t a i n e d on intravenous heparin t h r o u g h o u t their postoperative hospitalization. The heparin dose was adj u s t e d to maintain an activated partial thromboplastin time of 1.3-1.5 times control. All recipients received cyclosporine-based i m m u n o s u p p r e s s i o n therapy a n d were cared for by the same physicians. Those patients with p o o r renal function in the early postoperative period received quadruple sequential i m m u n o s u p p r e s s i o n using either ATGAM (Upjohn, Kalamazoo, MI) or OKT3 (Ortho Biotech Inc., Raritan, NJ) before c o m m e n c i n g cyclosporine therapy. Calculation of creatinine clearance. Recipient creatinine clearance was calculated using the Cockroft-Gault formula (19) : [140 - age (y)] [weight (kg)]* 72 [serum creatinine ( m g / d L ) ] * (females × 0.85).
Statistical analysis. Statistical analysis was perf o r m e d using SigmaStat (Jandel Inc., San Rafael, CA) and Statgraphics Plus 6.1 (Manugistics, Rockville, MD) statistical software packages. Differences between groups were calculated using the Student's t-test for parametric data and the MannWhitney rank-sum test for nonparametric data. Survival curves were d e t e r m i n e d using the KaplanMeier m e t h o d (20). Those patients who died with a functioning allograft were considered as a graft loss. Differences in survival between groups were d e t e r m i n e d using the log-rank test. Values of p < 0.05 were considered significant. Results
Recipient characteristics. The recipients in the pediatric- and adult-donor groups did n o t differ in regard to age, weight, gender, race, n u m b e r of patients with high panel reactive antibody, number of patients who had previous transplantations, or n u m b e r of diabetic recipients (Table 1). Eleven recipients (50%) of pediatric kidneys received quadruple sequential immunosuppression, as did 34 recipients (65%) in the adult-donor group (p = n o t significant).
Ratner Table 1. R e c i p i e n t Characteristics* Characteristic
Pediatric
Number Age (y) Weight (kg) Male Female Black White eRA > 10% Previous Tx Diabetes
Adult
22 45.2 ± 12.7 81.3 ± 23.7 15 (68.2%) 7 (31.8%) 13 (59.1%) 9 (40.9%) 1 (4.5%) 0 2 (9.1%)
52 44.6 + 11.7 75.4 -+ 17.2 31 (59.6%) 21 (40.4%) 26 (50.0%) 26 (50.0%) 1 (1.9%) 8 (15.4%) 13 (25.0%)
*There were no significant differences between the groups. PRA, panel reactive antibody; Tx, transplantation.
Pediatric-donor characteristics. Twenty-two patients received kidneys f r o m pediatric cadaveric organ d o n o r s aged -< 5 years. Ten o f these recipients received a single pediatric kidney a n d 12 received p a i r e d en bloc pediatric kidneys. Overall, the donors o f the kidneys transplanted as a pair en bloc t e n d e d to be y o u n g e r a n d smaller than the donors
e t al
TRANSPLANTATION OF PEDIATRIC KIDNEYS 4 3 9
of the kidneys transplanted as a single organ into a single recipient, but these differences in d o n o r age and size were not statistically significant (Table 2). Ischemic time and acute tubular necrosis. Cold ischemic time for the pediatric-donor group (29.30 -_ 8.25 hours) was significantly l o n g e r than that for the control group (23.88 _+ 11.53 hours) (p = 0.037). W h e n the pediatric group was stratified b e t w e e n recipients o f single a n d paired e n bloc kidneys, no difference in ischemic time was observed (Table 2). T h e incidence o f acute tubular necrosis (defined as the n e e d for dialysis d u r i n g the first week after transplantation) was 30.8% for the control group and 23.8% for the pediatric-donor c o h o r t (p = n o t significant). Patient and graft survival. T h e r e was no differe n c e in patient survival between the pediatricd o n o r a n d adult-donor groups. At 3 years, patient survival was 85.0% a n d 85.9% for the recipients o f
Table 2. C o m p a r i s o n o f P a t i e n t Characteristics a n d O u t c o m e s in t h e Two Groups*
Patient
Recipient race/ gender
Recipient weight (kg)
Donor race/ gender
Donor weight (kg)
Donor age (mo)
Cold ischemic time (h)
Acute tubular necrosis
Complication
Paired en bloc kidneys D.B.
W/F
45
W/F
20
45
35.35
No
W.C. J.C.
W/M B/M
95 78
W/M B/F
16 10.5
30 21
45.12 19.12
No Yes
D.F.
W/F
81
W/M
11
24
28.95
R.F. R.G. R.L. E.M. O.R. T.S.
B/M B/F B/M B/F W/F B/M
50 99 93 74 96 109
W/M W/F W/M W/M W/F W/F
14 15 17 12 15 12
36 36 42 33 47 36
23.00 33.47 26.78 30.83 39.75 27.57
No No No No No No
E.W.
B/M
79
B/M
8
26
18.60
Yes
E.W.
W/M 5W, 7B, 5F, 7M
94 82.8 ± 26.8
W/F 10W, 2B, 6F, 6M
20 14.2 -+ 3.7
52 35.7 -+ 9.6
22.92 29.0 + 7.6
No 18.2%
C.B. JJ. M.M. M.M.
W/M B/M B/F B/M
127 64 53 72
W/M W/M B/F B/F
16 20 32 20
51 69 61 38
28.75 35.95 8.30 26.32
No No No Yes
J.M. W.P. J.P. T.R. A.S.
B/M W/M B/M W/M B/F
112 79 70 69 54
B/F W/M W/F W/F W/F
11 18 16 12 20
24 70 30 31 71
42.63 25.38 38.48 28.17 28.85
Yes No No No No
B.S.
W/M 4W, 6B, 2F, 8M
116 81.6 -+ 26.8
W/F 8W, 2B, 7F, 3M
33.37 29.6 + 9.4
Yes 30.0
Mean
Acute rejection---~ graft thrombosis Cardiovascular death Hypotension--~graft thrombosis Ureteral stricture
Bladder leak (three ureters) Ureteral necrosis; late infectious death
Single pediatric kidneys
Mean
12 31 17.7 ± 6.1 47.6 ± 18.9
Focal segmental glomerulosclerosis
Ureteral necrosis; late infectious death
*The donors tended to be smaller and younger in the paired pediatric kidney group than in the single pediatric kidney group, but no statisticaldifference was observed for either weight or age. W, white; F, female; M, male; B, black.
440 J AM COLL SURe NOVEMBER1997
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100 90 80 70 60
............Pediatric D o n o r (n=22) A d u l t D o n o r (n=52)
50 40 30
-
20 10 0
I
0
I
1
I
2
p=NS
I
3
I
4
5
Years
FIG 1. Patient survival was similar for recipients for pediatric-donor (age --< 5 years) and adult-donor (age 18-55 years) kidneys (log-rank test, p = not significant).
pediatric-donor and adult-donor kidneys, respectively (Fig. 1). Similarly, no differences were observed in graft survival between the adult- and pediatric-donor groups. At 3 years, the calculated allograft survival was 76.4% for the recipients of pediatric-donor kidneys and 69.9% for the recipients of kidneys from donors aged 18-55 years (p = not significant) (Fig. 2). All causes of graft failure and patient death are listed in Table 3. The leading cause of graft loss in both the pediatric- and adult-donor groups was
death with a functioning allograft. Technical complications were an unusual cause of graft loss. Graft thrombosis occurred in one recipient of a paired en bloc pediatric allograft when the patient became hypotensive in the immediate postoperative period. One adult kidney had a renal artery thrombosis, presumably for technical reasons. No graft thrombosis was observed in the recipients of single pediatric kidneys. Urinary complications. Four recipients (18.2 % ) of pediatric k i d n e y s had urinary complications.
100 90 80 70 60
m
.........Pediatric D o n o r (n=22) - A d u l t D o n o r (n=52)
50 40 30 20
m
10 0
I
0 p=NS
I
1
I
2
I
3
I
4
5
Years
FIG 2. Graft survival was comparable for recipients for pediatric-donor (age --< 5 years) and adult-donor (age 18-55 years) kidneys (log-rank test, p = not significant).
R a t n e r et al Table 3. Causes of Graft Loss* Pediatric Cause
no
Death Graft thrombosis Acute rejection C h r o n i c rejection Primary n o n f u n c t i o n R e c u r r e n t disease *There
were no significant
no
13.6 4.5 4.5
differences
function, as d e t e r m i n e d by the calculated creatin i n e clearance. By 6 m o n t h s after transplantation, the recipients in the pediatric-donor group h a d significantly greater creatinine clearances than recipients in the adult-donor group: 76.1 -+ 24.0 versus 61.4 -+ 23.2 m L / m i n , respectively (p = 0.035) (Fig. 3). At 1 year after transplantation, creatinine clearance rates were 89.1 _+ 33.6 a n d 63.0 _+ 27.8 m L / m i n for the --< 5-year d o n o r group a n d the 1 8 - 5 5 - y e a r d o n o r group, respectively (p = 0.008). Similarly, at 2 years postoperatively, the creatinine clearances were 107.8 _+ 25.3 and 60.0 _+ 23.4 m L / m i n for the pediatric- and adult-donor groups, respectively (p < 0.001). Recipients of paired pediatric kidneys initially had better renal function (63.9 +- 21.4 m L / m i n ) than recipients of single pediatric kidneys (38.2 - 11.6 m L / m i n ) (p = 0.004), but by 6 months, no significant difference existed (Fig. 4). Hematocrit levels as a measure of erythropoiesis were similar for single pediatric, paired pediatric, and adult-donor recipients (Fig. 5). Proteinuria d e v e l o p e d after transplantation in f o u r recipients o f pediatric kidneys. In two patients, the p r o t e i n u r i a resolved spontaneously a n d so it was p r e s u m e d to be o f native kidney origin. Proteinuria abated in one recipient after an angiotensin-converting enzyme inhibitor was a d d e d to his antihypertensive regimen. Renal allograft biopsy d e m o n s t r a t e d focal segmental glomerulosclerosis in the final patient with proteinuria, but that patient continues to have g o o d renal function a n d is d o i n g well without dialysis.
Adult %
3 1 1 0 0 0
between
%
6 1 1 1 1 1
TRANSPLANTATIONOF PEDIATRIC KIDNEYS 441
11.5 1.9 1.9 1.9 1.9 1.9
the groups.
T h r e e of these patients had received paired e n bloc kidneys a n d one received a single pediatric kidney. T h e urinary complications in the paired en bloc group consisted of o n e ureteral stricture, o n e ureteral necrosis secondary to an invasive Candida infection, a n d one leak f r o m the anterior cystotomy in the patient who h a d a Po!itanoL e a d b e t t e r u r e t e r o n e o c y s t o s t o m y (18). The o n e urinary complication in a recipient o f a single pediatric kidney consisted o f a necrotic u r e t e r s e c o n d a r y to an invasive enterococcal infection. In the g r o u p that received allografts f r o m adult donors, ureteral distal tip necrosis developed in two patients (3.8%). In all cases, ureteral necrosis was treated p r o m p t l y by resection o f the allograft ureter, a n d a ureteropyelostomy was p e r f o r m e d using the ipsilateral native ureter. T h e one patient with a ureteral stricture h a d this c o r r e c t e d by percutaneous stenting. No grafts were lost f r o m urinary complications. Renal allograft function. Kidneys p r o c u r e d f r o m d o n o r s - 5 years o f age provided excellent renal 200 175
Pediatric
/x Adult
©
o 150 t'-
I I I..--'----.
o 125 ~D 0 CD c"
"~
[
IO0 75 5O
(D
25 0 *p=NS all others p
t
I [
1
i
i
i
i
i
i
, i
i
D
0.5
1.0
1.5
2.0
2.5
3.0
3.5
]-[me P o s t - T r a n s p l a n t (Years)
FIG 3. Comparison of pediatric- and adult-donor recipient calculated creatinine clearances (mL/min) over time. At the time of discharge, mean creatinine clearance was comparable between the groups, but by 6 months after transplantation, allograft renal function was significantly better in the pediatric-donor cohort.
442 J AM COLL SURe N O W M B E R 1997
VOLUME185:437--445
180 160
c~ 140 120 100 "E
~-~ Single
lPQired
[
T
l
80 60
(.3
40 20 0
*p=O.O04
e~
%
all others p=NS FIG 4. Calculated recipient creatinine clearance of the single-kidney pediatric-donor group versus the paired en bloc kidney pediatric-donor group. At the time of discharge, the paired kidneys provided approximately double the renal function of the single kidneys, but by 6 months after transplantation, there was no observable significant difference.
Discussion
The transplantation literature is replete with series from individual institutions a n d registry data that report p o o r e r results when kidneys from young pediatric donors are used (3, 5-10). Yet many authors have r e p o r t e d g o o d results when these kidneys are transplanted (14, 16, 21-23). There continues to be reluctance by many centers to transplant kidneys from donors aged -< 5 years into adult recipients. O n e major concern is the large disparity between d o n o r renal mass a n d recipient body mass. It has b e e n hypothesized that this large discrepancy between renal mass and body mass results in glomerular sclerosis secondary to hyperfiltration injury (2). There have been reports of focal segmental glomerulosclerosis developing in pediatric kidneys that were transplanted into adults (4, 5, 24, 25). In contrast, our experience indicates that the d e v e l o p m e n t of focal segmental glomerulosclerosis m pediatricd o n o r kidneys (4.5%) is probably an unusual occurrence. In addition, the judicious use of angiotensin-converting enzyme inhibitors in patients with systemic hypertension or proteinuria may be beneficial in preventing hyperfiltration lesions (26, 27). In any event, the progressive decline in renal function that would be predicted in the case of glomerular hyperfiltration injury was n o t observed. In our series, renal function c o n t i n u e d t o improve with time, and at 1 year after transplanta-
tion, the m e a n pediatric-kidney recipient creatinine clearance was greater than that obtained in the adult-donor group: 89.1 _+ 33.6 versus 63.0 + 27.8 m L / m i n , respectively (p = 0.008) (Fig. 4). Similar results were reported by N g h i e m and colleagues (12) for pediatric kidneys transplanted en bloc into adult recipients. In that study, the m e a n glomerular filtration rate increased from 22.5 + 14.2 to 85.3 +_ 52.3 m L / m i n by 6 m o n t h s a n d to 120.7 -+ 45.1 m L / m i n after 6 months. In the same series, renal allograft volume was n o t e d to have increased nearly threefold within 6 months. An incremental i m p r o v e m e n t in renal function was observed in both the single and paired en bloc pediatric cohorts in our series. Single pediatric kidneys initially provided approximately half the renal function of the en bloc paired kidneys, but rapidly achieved a similar level of function and c o n t i n u e d to perform well longterm. Primary n o n f u n c t i o n a n d acute rejection have been reported as problems in pediatric-donor kidneys (8, 10). This may reflect older series compiled before the introduction of current organpreservation techniques. An increased incidence of primary n o n f u n c t i o n was n o t observed in our patients. Alternatively, primary n o n f u n c t i o n may reflect severe acute rejection in the face of acute tubular necrosis. Indeed, rejection has been cited as the leading cause of graft loss for pediatricd o n o r kidneys (7, 10, 12, 15, 28). We used aggressive immunosuppressive therapy in the early post-
Ratner et al
TRANSPLANTATIONOF PEDIATRICKIDNEYS 443
55 50 45
•
Srngle Ped[Qtr[c
55
.
[
| /
- - - - - -
r
T
_..m ' ' m ' - n
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FIG 5. Recipient hematocrit levels as an indication of erythropoiesis were not different between the single and paired pediatric renal allografts. No significant difference in posttransplant hematocrit was observed between the pediatric-donor group and the adult-donor group (data not shown).
transplant period because pediatric kidneys may n o t tolerate a serious rejection episode as well as adult kidneys. An illustration of this was the one patient in our series who lost her allograft from acute cellular rejection. In that case, the allograft u n d e r w e n t thrombosis during an acute rejection episode > 1 m o n t h after transplantation, possibly because of increased resistance in small pediatric vessels. Allograft thrombosis and renovascular complications were n o t m a j o r problems in o u r series. O t h e r groups have reported an increased incidence of both allograft thrombosis (5) a n d renal artery stenosis (7, 10, 13). Like other investigators, we call attention to the importance of meticulous technical detail (13, 23, 29). For paired en bloc organs, a variety of techniques have been proposed to prevent torsion of the kidney on its vascular pedicle. These techniques have included fixi n g the allograft in Vicryl mesh (Ethicon, Somerville, NJ) (30), pexying the medial kidney to the bladder (13), and intraperitonealizing the medial kidney (23). We have n o t used these modifications and have n o t yet f o u n d torsion of the kidney to be a problem. Urinary complications have been n o t e d to be a p r o b l e m with these small kidneys (4, 5, 10, 13). In our series, 4 of 22 recipients (18.2%) of pediatric kidneys experienced urinary complications, but no grafts were lost after p r o m p t and aggressive m a n a g e m e n t . Hayes and coworkers (31) advocated the routine use of ureteral stents for renal
allografts p r o c u r e d from donors < 6 years of age. O u r experience indicates that this r e c o m m e n d a tion is prudent. O n the basis of this review, we have altered our practice to include the routine use of ureteral stents in pediatric-donor kidneys. The extreme shortage of organs for transplantation requires that use of these pediatric kidneys be optimized. The previous c o m p a r i s o n by Gruessner and colleagues (15) of single versus paired pediatric kidneys showed better graft survival in paired en bloc kidneys, but overall m o r e patients r e m a i n e d off dialysis with functioning kidneys if they received a single kidney. Other series have d e m o n s t r a t e d acceptable results with single pediatric kidneys (8, 10, 21, 22, 32, 33). The use of paired pediatric kidneys has r e m a i n e d theoretically attractive because of the concern about hyperfiltration injury. Yet pediatric kidneys have been d e m o n s t r a t e d to grow rapidly when transplanted into adults (12, 14). O u r data indicate that a good "low mileage" pediatric kidney may provide even better function than an adult kidney if allowed to grow without early insults such as acute rejection. Because comparable results can be obtained with single versus en bloc pediatric kidneys, there is little justification for using en bloc kidneys. O n e caveat is that in the present series, we did n o t randomize the en bloc and single pediatric donors. In general, the en bloc donors were slightly younger and smaller than the donors of kidneys transplanted individually (Table 2). Several reports have d e m o n s t r a t e d good results with
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kidneys from children 3-5 years of age, but p o o r e r results with kidneys from donors -< 3 years o l d (6, 8-10). We would be cautious when using individual kidneys from very small donors. With the growing disparity between organ supply and d e m a n d , kidneys from donors > 60 years of age have been transplanted with increasing frequency and a c c o u n t e d for 6% of cadaveric renal transplantations in the United States in 1993, as o p p o s e d to 2% in 1988 (34). W h e n viewed from this perspective, pediatric d o n o r kidneys yield better results than those obtained with organs from older donors. United Network for Organ Sharing registry data have reported renal allograft halflives of 8.8 years a n d 5.0 years for donors --< 5 years and > 60 years of age, respectively (p < 0.001) (34). In fact, U n i t e d Network for Organ Sharing registry data indicated that the allograft half-life for organs from donors aged --- 5 years compares favorably with that obtained with donors aged 4 6 - 6 0 years, and is comparable to that resulting from transplanting cadaveric kidneys from adult donors 31-45 years of age (34). In summary, the transplantation of kidneys from young pediatric donors -< 5 years of age can result in both patient and allograft survival that is comparable to that achieved with organs p r o c u r e d from adult cadaveric donors. Allograft functional adaptation occurs rapidly for both single and paired pediatric kidneys when transplanted into adult recipients. In fact, pediatric d o n o r kidneys provide better recipient creatinine clearance than do adult-donor renal allografts. Ureteral complications were m o r e frequent in the pediatric-donor group but did n o t negatively affect graft survival. We conclude that kidneys from pediatric donors -< 5 years of age are suitable for transplantation into adults and should be used when available. There appears to be no advantage to transplanting these young d o n o r kidneys as a pair en bloc. To make optimal use of these kidneys, this practice should be discouraged and individual pediatric kidneys should be used for individual recipients. References 1. Fine RN. Renal transplantation of the infant and young child and the use of pediatric cadaver kidneys for transplantation in pediatric and adult recipients. Am J Kidney Dis 1988;12: 1-10. 2. Brenner BM, Cohen RA, and Milford EL. In renal transplantation, one size may not fit all.j Am Soc Nephrol 1992;3:162169. 3. Terasaki PI, Koyama H, Cecka JM, and Gjertson DW. The hyperfiltration hypothesis in human renal transplantation. Transplantation 1994;57:1450-1454. 4. Hayes JM, Steinmuller DR, Streem SB, and Novick AC. The
5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28.
development of proteinuria and focal-segmental glomerulosclerosis in recipients of pediatric donor kidneys. Transplantation 1991;52:813-817. Neumayer HH, Huls 8, Schreiber M, et al. Kidneys from pediatric donors: risk versus benefit. Clin Nephrol 1994;41: 94-100. Creagh TA, McLean PA, Spencer S, et al. Transplantation of kidneys from pediatric cadaver donors to adult recipients. J Urol 1991;146:951-952. Gourlay W, Stothers L, McLoughlin MG, et al. Transplantation of pediatric cadaver kidneys into adult recipients. J Urol 1995;153:322-325. Ildstad ST, Tollerud DJ, NoseworthyJ, et al. The influence of donor age on graft survival in renal transplantation.J Pediau Surg 1990;25:134-139. Ruder H, Schaefer F, Gretz N, et al. Donor kidneys of infants and very young children are unacceptable for transplantation. Lancet 1989;2:168. Wengerter K, Tellis V, Soberman R, et al. Transplantation of pediatric donor kidneys to adult recipients: is there a critical donor age? Ann Surg 1986;204:172-175. Schneider JR, Sutherland DER, Simmons RL, et al. Longterm success with double pediatric cadaver donor renal transplants. Ann Surg 1983;197:439-442. Nghiem DD, Hsia S, and SchlosserJD. Growth and function of en bloc infant kidney transplants: a preliminary study. J Urol 1995;153:326-329. Merkel FK, Matalon TAS, Bru.nner MC, et al. Short- and long-term results with en bloc transplantation of pediatric kidneys into adults. Transplant Proc 1993;25:2167-2169. Ratner LE, and Flye MW. Transplantation of en-bloc pediatric kidneys into adult recipients. Transplantation 1991;51: 273-274. Gruessner RWG, Matas AJ, Lloveras G, et al. A comparison of single and double pediatric cadaver donor kidneys for transplantation. Clin Transplant 1989;3:209-214. van der Vliet JA, Cohen B, and Kootstra G. Transplantation of pediatric cadaver kidneys. Transplant Proc 1982;14:74-76. Lich R, Howerton LW, and Davis LA. Recurrent urosepsis in children. J Urol 1961;86:554-558. Weil R, Simmons RL, Tallent MB, et al. Prevention of urological complications after kidney transplantation. Ann Surg 1971;174:155. Cockroft DW, and Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976;16:31-41. Kaplan EL, and Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958;53:457. Abouna GM, Kumar MSA, Brezin J, et al. Transplantation of single pediatric cadaveric kidneys into adult recipients. Transplant Proc 1993;25:2170-2171. Boczko S, Tellis V, and Veith F. Transplantation of children's kidneys into adult recipients. Surg Gynecol Obstet 1978;146: 387-390. Nghiem DD. En bloc transplantation of kidneys from donors weighing less than 15 kg into adult recipients. J Urol 1991; 145:14-16. Woolley AC, Rosenberg ME, Burke BA, and Nath KA. De novo focal glomerulosclerosis after kidney transplantation. AmJ Med 1988;8~4:310-314. Leunissen KML, Kootstra G, Bosman FT, and van HooffJP. Focal glomerulosclerosis in neonatal kidney grafts. Lancet 1987;2:1019-1020. Heeg JE, de Jong PE, van der Hem GK, and de Zeeuw D. Reduction of proteinuria by angiotensin converting enzyme inhibition. Kidney Int 1987;32:78-83. Anderson S, Meyer TW, Rennke HG, and Brenner BM. Control of glomerular hypertension limits glomerular injury in rats with reduced renal mass. J Clin Invest 1985;76:612=619. Smith AY, van Buren CT, Lewis RM, et al. Short-term and long-term function of cadaveric kidneys from pediatric donors in recipients treated with cyclosporlne. Transplantation 1988;45:360-367.
Ratner
29. HayesJM. The transplantation of difficult donor kidneys and recipients: helpful surgical techniques. J Urol 1993;149:250254. 30. Lowell JA, Cattral MS, Freel MS, et al. Use of a Vicryl mesh envelope to prevent vascular occlusion of pediatric donor kidney transplants. Transplant Proc 1994;26:39-41. 31. Hayes JM, Novick AC, Streem SB, et al. The use of single pediatric cadaver kidneys for transplantation. Transplantation 1988;45:106-110.
e t al
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32. Glass NR, Stillman RM, Butt KMH, and Kountz SL. Results of renal transplantation using pediatric cadaver donors. Surgery 1979;85:504-508. 33. Kootstra G, West JC, Dryburgh P, et al. Pediatric cadaver kidneys for transplantation. Surget3~ 1978;83:333-337. 34. CeckaJM, and Terasaki PI. The UNOS scientific renal transplant registry. In: CeckaJM, Terasaki PI, eds. Clinical Transplants 1994. Los Angeles: UCLA Tissue Typing Laboratory; 1995:1-18.