Pre-Emptive Pediatric Kidney Transplantation or Not?

C.D. Garciaa,b,*, V.B. Bittencourta, R.W. Rohdea, S. Dickela, I. Piresa, K. Tumbaa, S.P. Vitolac,
V. de Souzad,e, M. Wagnere, and V.D. Garciac
a
Pediatric Nephrology Unit, Departament of Nephrology, Hospital da Criança Santo Antonio, Santa Casa Porto Alegre, Brazil;
b
Nephrology Department, Universidade Federal Ciências da Saude Porto Alegre, Porto Alegre, Brazil; cTransplant Unit, Hospital Dom
Vicente Scherer, Santa Casa Porto Alegre, Porto Alegre, Brazil; dUniversidade de Caxias do Sul, Brazil; and ePrograma de Pós
graduação em Saúde da Criança e do Adolescente, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

ABSTRACT
Background. Kidney transplantation prior to dialysis (pre-emptive kidney transplantation,
PKT) has been controversial because of the paucity of clinical evidence to clarify the risks
and benefits of PKT. Several authors have confirmed a significant advantage of PKT in the
treatment of patients with end-stage renal disease (ESRD). The aim of this study was to
examine the characteristics of patients who received PKT or nonepre-emptive kidney
transplant (NPKT).
Methods. We used a cohort of 323 consecutive kidney-transplanted children (53% boys) from
Hospital da Criança Santo Antonio, Porto Alegre, Brazil, who underwent transplantation
between January 2000 and December 2010.
Results. The main causes of ESRD were congenital anomalies of the kidney and urinary
tract (CAKUT) (39%) and glomerulopathies (27.5%). The 12-, 36-, 60-, and 90-months
death-censored graft survival rates were 97%, 92%, 86%, and 76%, respectively, in the
PKT group, and 87%, 79%, 72%, and 65% in the NPKT group (P < .05).
Conclusions. The results of this study suggest that pre-emptive transplantation is
beneficial (hazard ratio ¼ 0.37; 95% confidence interval: 0.18e0.82). The main causes of
graft loss (n ¼ 67) were recurrence of primary disease (21%), chronic allograft injury
(17%), and death with a functioning graft (16%). We recommend PKT as a better
choice for transplantation whenever possible to minimize ESRD morbidity and provide
better long-term patient and graft survival.

O F the available renal replacement therapies for children

with end-stage renal disease (ESRD), only kidney
transplantation (KT) offers the possibility of restoring normal
renal function, thereby eliminating many of the manifestations
of significantly impaired kidney function [1].
The best results are seen in patients transplanted prior to
starting dialysis, otherwise known as pre-emptive kidney
transplant (PKT). Several authors have observed that the
time spent on dialysis decreases patient and graft survival
[2]. However, there are some theoretical disadvantages in
pre-emptive transplantation. These include the failure to
maximize the use of native kidney function, and it has been
suggested that adherence to immunosuppressive medica-
tions after transplantation may be reduced if patients do not
first experience the morbidity of dialysis.
The aim of this study was to examine the characteristics of
patients who receive PKT or nonepre-emptive kidney
transplant (NPKT) and to analyze the effect of pre-emptive
transplantation with the use of kidneys from living or
cadaveric donors on the outcomes.
METHODS
Patients
This cohort consisted of 323 consecutive kidney-transplanted children
from Hospital da Criança Santo Antônio, Porto Alegre, Brazil, who
underwent transplantation between January 2000 and December 2010.
*Address correspondence to Clotilde Druck Garcia, Correa
Lima 1493, Porto Alegre, Brazil 90850-250. E-mail:
cdruckgarcia@gmail.com

0041-1345/15 ª 2015 by Elsevier Inc. All rights reserved.

http://dx.doi.org/10.1016/j.transproceed.2015.03.019 360 Park Avenue South, New York, NY 10010-1710

954 Transplantation Proceedings, 47, 954e957 (2015)

PRE-EMPTIVE PEDIATRIC KIDNEY TRANSPLANTATION OR NOT? 955

Table 1. Baseline Characteristics of the Children With Kidney Transplant

Characteristics All PKT NPKT P

n 323 81 242 <.01

Male patients, n (%) 171 (53) 52 (64) 119 (49) .03
Age, years, median (IQR) 11.0 (7.0e14.0) 10.0 (7.0e13.5) 11.0 (7.0e14.0) .3
Primary diagnosis, n (%)
CAKUT 126 (39) 41 (50) 82 (35) .01
Glomerulopathy 89 (27.5) 13 (16) 76 (31) .01
Other 108 (33.5) 27 (34) 81 (34) .9
Deceased donor, n (%) 165 (51) 32 (40) 133 (55) .02
Graft loss, n (%) 67 (20) 7 (9) 60 (25) <.01
Recurrence disease 14 (21) 2 (28.5) 12 (20) .5
Death with a functioning graft 12 (18) 0 12 (20) .09
Chronic allograft nephropathy 11 (16) 2 (28.5) 9 (15) .8
Vascular thrombosis 5 (7) 2 (28.5) 3 (5) .8
Other 25 (37) 1 (14.5) 24 (40) .02
Abbreviations: IQR, interquartile range; PKT, pre-emptive kidney transplant; NPKT, nonepre-emptive kidney transplant.

We collected data on donor, recipient, and transplantation char- ESRD, and the remaining underwent peritoneal dialysis (55%)
acteristics that have previously been reported to influence allograft or hemodialysis (20%) before kidney transplant.
survival. Patient survival was defined as the time from transplant to
death or last follow-up. Death-censored graft survival was defined
as the time from transplant to the earliest time of graft loss, re- Graft Survival
transplantation, re-initiation of dialysis, or last follow-up with a Because the PKT group had just 90 months of follow-up,
functioning graft, censored for death. the survival analysis was censored at this time. The 12-,
36-, 60-, and 90-month death-censored graft survival rates
Statistical Analyses
adjusted by donor type were 97%, 92%, 86%, and 76%,
Statistical analyses reporting the demographic features of the respectively, in the PKT group, and 87%, 79%, 72%, and
recipients and donors was performed with descriptive statistics 65% in the NPKT group (P < .05). The median IQR
followed by 2-sided independent t tests for continuous variables and follow-up time was 36 (13e68) months in the PKT group
c2 analysis or Fisher exact test for categorical variables. The pri- and 42 (17e69) months in the NPKT group. The PKT
mary outcome of interest was graft survival, which was based on
group had 0.37 (95% confidence interval: 0.18e0.82) times
having pre-emptive transplantation or not having pre-emptive
the hazard of graft loss compared with those of the NPKT
transplantation. Secondary outcomes included donor status
(deceased or living). Data were presented as mean  standard group (P ¼ .03), adjusted for donor type, recipient sex and
deviation (SD), unless otherwise indicated. Differences in allograft age, and primary diagnosis. The rate of graft loss was on
survival rates were compared through the use of Kaplan-Meier average 12 months faster in the nonepre-emptive group.
curves, log-rank test, and Cox regression with hazard ratios, fol- There was also significant difference in patient survival
lowed by 95% confidence intervals. The Cox model was also used to
investigate whether the occurrence of graft loss could be explained
by differences at baseline. The variables considered for inclusion in
the model were donor type and age, recipient sex and age, and
primary diagnosis. All analyses were performed with the use of R
for windows, version 3.1.0. A value of P < .05 was considered sta-
tistically significant.

RESULTS
Patient Population
The characteristics of the 323 patients (53% men) are shown in
Table 1. The median age [interquartile range (IQR)] was 10.0
years [7.0e13.5] in the PKT group and 11.0 years [7.0e14.0] in
the NPKT group, and there was no difference between the
groups (Fig 1A). The proportion of living donors was higher in
the PKT group (60%) than in the NPKT group (45%, P ¼ .02) Fig 1. Frequency distribution of pre-emptive transplant (PKT)
(Fig 1B). The main causes of end-stage renal disease (ESRD) and nonepre-emptive kidney transplant (NPKT). (A) Box plot of
were congenital anomalies of the kidney and urinary tract age distribution between PKT and NPKT; (B) bar plot of PKT
(CAKUT) (39%) and glomerulopathy (27.5%). Eighty-one and NPKT groups according to donor type: living donor (LD) or
patients (25%) underwent KT as the first treatment for deceased donor (DD).
956
Fig 2. Graft survival curves of nonepre-emptive kidney trans-
plant (NPKT) and pre-emptive kidney transplant (PKT).
rates between the two groups (P ¼ .02), but there was no
difference in graft survival rates according to donor type
(living or deceased) (P ¼ .6). The main causes of graft loss
(n ¼ 67) were recurrence of primary disease (21%),
chronic allograft injury (17%), and death with a func-
tioning graft (16%). The main cause of death was infection,
which accounted for 50% of cases.
DISCUSSION
In this study, 323 pediatric patients received PKT (25%) or
NPKT (75%). Our findings demonstrated that the graft and
patient survival rates adjusted by donor type in NPKT at 90
months after transplant were significantly lower when
compared with PKT, as shown in Fig 2 (log-rank test, P <
.05). Occurrence of graft loss in the NPKT group was 12
months faster than that seen in the PKT group. The pop-
ulation studied here presented no difference in graft sur-
vival according to donor type; however, Pitt et al [3] found a
superior graft survival in a living donor group.
In the past 10 years, graft and patient survival rates have
been compared between recipients of PKT and those of
NPKT in different studies, and the outcomes have been
shown to be comparable or even better for PKT [4e7]. The
PKT for children avoids the complications associated with
acute or cuffed catheters and fistulas as well as minimizes
other morbidities associated with ESRD and dialysis, such as
bone disease, anemia, and growth failure. Pre-emptive
transplantation must be considered in every child at the
diagnosis of ESRD. Children with irreversible stage 4 chronic
kidney disease should be pushed for pre-emptive trans-
plantation unless there is a contraindication. The main
requisite for PKT is the availability of a donor. Until 2009 in
Brazil, children on the waiting list for a kidney transplant
received extra points compared with adults. After 2009, a
new government act gave priority to children when the donor
was 18 years of age or younger (“Share 18”) [8]. This act also
GARCIA, BITTENCOURT, ROHDE ET AL
permitted children to be wait-listed pre-emptively, with a
glomerular filtration rate of 15 mL/min or less, which favored
and increased pediatric renal transplantation in our country.
Children with congenital renal dysplasia are the best
candidates to undergo transplantation pre-emptively.
Exclusion criteria for pre-emptive transplantation include
heavy proteinuria, chronic infection, and resistant hyper-
tension. Evidence shows that patients who undergo trans-
plantation at the time of active nephrotic syndrome have a
greater chance of clotting their new allograft [9].
In conclusion, the results of this study strongly suggest
that pre-emptive transplantation is beneficial. However, the
benefits of pre-emptive transplantation do not appear to be
shared equally among transplant recipients. Thus, there are
reasons to encourage pre-emptive transplantation [10,11].
Although pre-emptive transplantation is associated with
less delayed graft function and better long-term patient and
graft survival, these statistical associations between pre-
emptive transplantation and improved outcomes do not
establish a causal relationship. Rather, the true effect of
pre-emptive transplantation on outcomes could only be
proven in randomized trials, and such trials are not likely to
be conducted [12].
CONCLUSIONS
Pre-emptive transplantation offered significantly better pa-
tient and graft survival in this group of patients, and the benefit
of avoiding or minimizing the morbidity of dialysis reinforces
the importance of early pre-emptive transplantation whenever
possible. There may also have other advantages or even dis-
advantages not addressed in the present study. In the absence
of randomized trials, multiple covariates to account for other
differences in pre-emptive transplantation, which could have a
more direct effect on graft survival, should be used. It should
be emphasized that pre-emptive transplantation is per se
beneficial, and we recommend it as the better choice whenever
possible.
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