Kidney International, Vol. 40 (1991), pp.

752756

Long-term results of renal transplantation in children

DONALD E. POTTER, JOHN NAJARIAN,' FOLKERT BELZER,2 MALCOLM A. HOLLIDAY,
GLORIA HORNS, and OSCAR SALVATIERRA, JR.
Departments of Pediatrics and Surgery, University of California, San Francisco, San Francisco, California, USA

Long-term results of renal transplantation in children. The results of

renal transplantation in 37 children, 3 through 16 years of age, who
received transplants prior to June, 1970 in our center, were examined.
Twenty-three received kidneys from living-related donors and 14 re-

1964 and May 1970. Seven children were less than six years of
age. The causes of renal failure were chronic glomerulonephri-

ceived kidneys from cadaver donors. Patient survival rates were 78% at
10 years and 68% at 20 to 26 years. Graft survival rates were 56% at 10

tumor in 4, dysplasia in 3, rapidly progressive glomerulonephri-

years, 31% at 20 years, and 23% at 22 to 26 years. Twenty children

received on or more retranspiants. At follow-up, 23 (62%) of the

patients had functining grafts and two (5%) were undergoing dialysis.

Cataracts, hypertension, and aseptic necrosis of bone were the most

common medical complications and most of the patients were more
than two standard deviations below average height. Most enjoyed good
rehabilitation, however: more than 70% were employed or performing
full time housework, more than 50% were married, 24% had children,

and all had normal activity at least part of the time. These results,
achieved with immunosuppressive methods now considered obsolete,
indicate that renal transplantation is a satisfactory long-term treatment
for children with renal failure.

The first renal transplant between identical twins was performed in 1954, and the first successful transplant between
non-identical individuals was performed in 1959 [1]. Although
the results in the early years of transplantation were generally
poor, a number of patients have survived for prolonged periods
after receiving a transplant. some with the original kidney still
functioning. There is little information regarding the long-term

results of transplantation, in either children or adults. The

present report describes results in children who received transplants in our institution from 1964 to 1970, and therefore have

been followed for at least twenty years. Patient and graft

tis in 15 children, reflux nephropathy in 4, bilateral Wilms'

tis in 3, obstructive uropathy in 2, and HenOch-Schnlein

nephritis, hemolytic-uremic syndrome, cystinosis, congenital
nephrotic syndrome, medullary cystic disease, and nail-patella
syndrome in 1 each. Fourteen children received kidneys from
cadaver donors and 23 children received kidneys from living
related donors, of whom 17 were parents, 2, siblings (1 HLA
identical), 2, grandparents, 1, half-sibling, and 1, uncle.
Details of the surgical techniques and immunosuppressive
regimen have been published previously [2]. Immunosuppression at transplantation was azathioprine, 2 mg/kg, which was
continued indefinitely, and prednisone, 2 mg/kg, with subsequent tapering of the dose; recipients of cadaver kidneys also
received irradiation of the graft and actinomycin C for three
days. Rejection episodes were treated with increased doses of
prednisone, irradiation of the graft, and actinomycin C. Splenectomies were performed in 32 of the children.
Twenty patients received second transplants and three patients received third transplants. Nineteen of these transplants
were performed using cadaver grafts and immunosuppression
included cyclosporine after seven of the transplants.
All surviving patients were followed for at least twenty years.
Patient and graft survival rates were calculated for the 26 year

survival rates are analyzed, the status of children ten years after period of this report. Survival rates for the first 20 years

transplantation is examined and their subsequent course described, and the rehabilitation, growth, and renal function of
children surviving more than twenty years after transplantation
are considered.
Methods

represent actual rates whereas rates between 20 and 26 years

were calculated by actuarial methods [3]. In the analysis of graft
survival, patients dying with functioning grafts were considered
to have undergone graft failure.
Follow-up information was obtained on all surviving patients

in June 1990, and included assessments of general health,

Patients
Thirty-seven children (16 boys, 21 girls), ages 3 through 16 medical complications, serum creatinine level, height, employyears (mean 9.4 years) received renal transplants between April ment status, and marital status. All of the patients were
interviewed, either in person or by telephone, and were asked
to define their level of activity by one of the five categories
'Current address: Department of Surgery, University of Minnesota, described in the Karnovsky activity scale [4]. The ages of the
Minneapolis, MN.
2 Current
patients were 23 to 40 years (mean 32.0 years).
address: Department of Surgery, University of Wisconsin,
Growth was assessed by changes in standard deviation scores
Madison, WI.
Received for publication March 6, 1991
and in revised form May 17, 1991
Accepted for publication May 17, 1991

1991 by the International Society of Nephrology

for height [5]. The height of each child was measured at

transplantation and when he or she stopped growing and was
expressed as the number of standard deviations from the mean
height of normal children of the same age and sex.

752

753

Potter et a!: Renal transplantation in children

100
29

80

29
26

25

a,

>

Patient survival

60
'1)

C
a,

40

20

15

10

25

20

Time, years post-transplant

Table 1. Causes of death in relation to time after transplantation

No. of deaths by time period after
transplantation
Cause

<1 year

13 years

Infection
5
ia

I
Operative

Wilms' tumor
1

Cerebral hemorrhage

Skin cancer

Hyperkalemia (dialysis)
a Occurred < one year after a second transplant

1026 years

Fig. 1. Patient and graft survival rates for 37

children after transplantation. Numbers above the
lines refer to number of patients or grafts at risk.

Status
Functioning first

Number of patients at
10 years

2026 years

20

10

graft

Statistical analysis
Data are expressed as means so. Comparison of means
between groups was by Students unpaired t-test and comparison of means within groups was by Student's paired t-test.

7
5

Functioning second 6
or third graft

Dialysis

Results
Twenty-five of the 37 children were alive at follow-up, 20 to
26 years after transplantation. Cumulative patient survival rates

were 78% at 10 years and 68% at 20 to 26 years (Fig. 1). The

survival rate at 20 years was 78% for children who received

living-related donor transplants and 50% for children who

received cadaver donor transplants.
Infection was the primary cause of death, accounting for six
deaths occurring within the first three years after transplanta-

Dead

Fig. 2. The status of37 children ten years after transplantation and at
follow-up.

tion and one death occurring 13 years after transplantation ing grafts decreased only slightly during the second decade,
(Table 1). Seven deaths occurred in recipients of cadaver from 70% to 62%.
kidneys, five of whom were less than six years of age. Three of
In the patients whose primary grafts continued to function,
these children had previous Wilms' tumors.
the mean serum creatinine level increased from 1.18 0.24
Cumulative graft survival rates were 56% at 10 years, 31% at
20 years, and 23% at 22 to 26 years (Fig. 1). The survival rate at

mg/dl at ten years to 2.06

1.53

mgldl at follow-up (P = 0.10).

Two of the patients, one who received a graft from an HLAidentical donor, and the other who received a graft from a
haplo-identical donor, had taken no immunosuppressive drugs
for ten years. The mean serum creatinine level of the patients
with functioning second or third transplants at follow-up was

20 years was 35% for living-related donor grafts and 21% for
cadaver grafts. Actuarial graft survival rates of the 23 retransplants were 49% at 10 years and 37% at 15 years.
The status of the children ten years after transplantation and
at follow-up is shown in Figure 2. Ten of the 20 primary grafts 1.22 0.36 mg/dl.
functioning at ten years subsequently failed, in three instances
The medical complications in the 25 surviving patients at
after patients discontinued immunosuppressive drugs. Most of follow-up are listed in Table 2. Five of the 23 patients with
the patients whose grafts failed received successful retrans- functioning grafts had symptomatic medical problems, aseptic
plants, however, and the percentage of children with function- necrosis of bone in four and relapsing pancreatitis in one, and

754

Potter et a!: Renal transplantation in children

Table 2. Complications in the 25 patients at follow-up

Number of patients

Cataracts
Hypertension
Aseptic necrosis
Relapsing pancreatitis
Ureteral obstruction
Skeletal deformities
Urinary tract infection
Arrhythmia
Seizure disorder

14
5

4
I
I
I

Polymyositis
Depression

Table 3. Physical activity of the 25 patients at follow-up according to

Karnovsky category
Patients with Patients
Patients
on
with
primary
grafts
retransplants dialysis
Number of patients
Activity scale
90100

1
1
1

8089

7079

the 23 patients with functioning grafts and one of the two

patients undergoing dialysis were employed or performing
full-time housework (Table 4). More than one-half of the
patients were married and six had children (Table 4).
The mean height standard deviation score of the children at
transplantation was 1.82 1.77 and at follow-up was 2.43
1.40, a change which just reached statistical significance (P =
0.05). The mean height standard deviation score did not change
between transplantation and follow-up in the patients whose
primary grafts continued to function (2.14 1.64 and 2.17
1.76, respectively), but decreased significantly in those who
required retransplants or were undergoing dialysis (1.61
1.88 and 2.60
1.17, respectively, P <0.05).

10

least part of the

4069

one of the two patients undergoing chronic dialysis was symptomatic with polymyositis and a mild depressive disorder. All of
the patients were active, achieving activity ratings of 90 to 100
or 80 to 89 on the Karnovsky activity scale (Table 3). Fifteen of

Almost normal
physical activity
Normal activity at

139

time
Only self-care
activities
Requires help in
self-care
Institutionalized

Table 4. Employment and marital status of the 25 patients at

follow-up
Patients
Patients
Patients with
on
with
primary
retransplants
dialysis
grafts
Number of patients
Employment status
Employed
Full-time housework
Unemployed
Marital status
Married
Divorced
Single
Patients with children

7
0
6
3

4
3

0
1

Discussion

In our center, 68% of children who had received renal

transplants more than twenty years previously were alive, 27% may also have contributed to the high mortality rate, but there
with the original kidney still functioning. Most of the patients was no difference in the incidence of infectious deaths in
were healthy and leading productive lives, demonstrating that splenectomized and non-splenectomized patients, and after we
transplantation can be a successful long-term treatment for adopted a policy limiting the amount of immunosuppression
children with renal failure.
used to treat rejection episodes [19], the mortality rate following
A number of transplant centers have reported their results second and third transplants was low.
extending more than ten years after transplantation [616], but
The late mortality rate, in patients surviving more than ten
there is little information on survival past twenty years, either years after transplantation, was also low, 14%, which compares
in adults or children. The longest reported experience is that of with mortality rates of 20% to 30% reported in adult patients
transplants between identical twins in Boston [91; for thirty during the second decade after transplantation [10, 12, 14, 15].

patients who received transplants between 1954 and 1976, The lower mortality rate in our patients could simply be the
actuarial patient and graft survival rates at 25 years were 66% result of sampling error in a small group or could reflect the
and 55%, respectively. For recipients of non-twin transplants, younger age of our patients, since cardiovascular disease,
20-year actuarial patient and graft survival rates of 53% and which is the most frequent cause of late deaths in adults
19%, respectively, have been reported [15]. In the most extensive pediatric experience [16], 45% of patients were alive and
26% of grafts were functioning 10 to 25 years after transplantation.
In our center, the mortality rate was high during the first year
after transplantation, in an era when high doses of corticoste-

roids were used to treat rejection episodes and infections

complications were common. Most of the early deaths occurred
in recipients of cadaver grafts, and the highest mortality rates
were in groups known to be at greatest risk, children less than
six years of age [17] and children with previous Wilms' tumors
[181. The fact that most of the children underwent splenectomy

following transplantation [1012, 14, 15] was the cause of death

in only one of our children. In the only report of long-term

pediatric survivors [16], the mortality rate after ten years was
21%, and although none of the deaths was attributed to cardio-

vascular causes, three patients had either coronary artery

disease or cerebrovascular disease at follow-up.
Although the mortality rate after ten years was low, graft loss
after ten years, primarily from chronic rejection, was a continu-

ing problem. It has previously been shown that there is a

constant rate of graft loss after the second year following
transplantation [20] although these calculations were based on

data extending less than ten years. The results in our small

Potter et a!: Renal transplantation in children

series suggest that the same rate of graft loss continues through
the second decade after transplantation, and might imply that
all grafts will eventually be lost. Other centers have reported a
lower rate of graft loss during the second decade, however, and

the maintenance of stable renal function in the majority of

755

proved short-term outcomes are extended into the second

decade after transplantation, it can be anticipated that children
currently undergoing transplantation will enjoy even better
long-term survival and rehabilitation than the subjects of this
report.

long-term survivors [11, 12, 14, 15]. In comparing our results

Acknowledgments
with those from adult programs, it may be pertinent that 30% of
We are indebted to the late Dr. Samuel Kountz for his outstanding
late graft losses in our center occurred in patients who discon- contributions
to this program and to the many other physicians and

tinued immunosuppressive therapy, reflecting the fact that

nurses who provided care to the children.

patient non-compliance is particularly prevalent in the pediatric

population [21]. Two of our patients who had discontinued

Reprint requests to Donald E. Potter, M.D., University of California,

Francisco, 533 Parnassus Avenue, Room U585, San Francisco,

immunosuppressive drugs ten years previously had good renal San
California 94143-0314, USA.
function at follow-up, however, indicating that immunologic
tolerance to transplanted kidneys can develop.
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