American Journal of Transplantation 2004; 4: 378–383
C Blackwell Munksgaard 2004
Blackwell Munksgaard
Lack of Improvement in Renal Allograft Survival
Despite a Marked Decrease in Acute Rejection Rates
Over the Most Recent Era
Herwig-Ulf Meier-Kriesche∗ , Jesse D. Schold,
Titte R. Srinivas and Bruce Kaplan
University of Florida, College of Medicine, Division of
Nephrology, Gainesville, FL
∗ 1996, both acute rejection rates and graft survival rates
Corresponding author: Herwig-Ulf Meier-Kriesche,
Meierhu@medicine.ufl.edu
Acute rejection is known to have a strong impact on
graft survival. Many studies suggest that very low
acute rejection rates can be achieved with current im-
munosuppressive protocols. We wanted to investigate
how acute rejection rates have evolved on a national
level in the U.S. and how this has impacted graft sur-
vival in the most recent era of kidney transplantation.
For this purpose, we analyzed data provided by the
Scientific Registry of Transplant Recipients regarding
all adult first renal transplants between 1995 and 2000.
We noted a significant decrease in overall acute rejec-
tion rates during the first 6 months, during the first
year, and also in late rejections during the second year
after transplantation. Despite this decrease in the rate
of acute rejection, there was no significant improve-
ment in overall graft survival; furthermore, we noted
a statistically significant trend towards worse death-
censored graft survival. There was also a trend for a
greater proportion of rejection episodes to fail to re-
cover to previous baseline function after treatment.
Our data suggest that decreasing acute rejection rates
between 1995 and 2000 have not led to an increase in
long-term graft survival. Part of this discordance might
be related to a higher proportion of acute rejections
which have not resolved with full functional recovery
in more recent years. However, the etiology of this con-
cerning trend for worse death censored graft survival
in recent years will warrant further investigation.
Key words: Acute rejection, era effect, graft survival,
kidney transplantation
Received 6 August 2003, revised and accepted for pub-
lication 8 October 2003
Introduction
Acute rejection has been shown to be one of the strongest
negative prognostic factors for long-term graft survival af-
378
Copyright 
doi: 10.1111/j.1600-6143.2004.00332.x
ter kidney transplantation (1–5). These studies implied that
a reduction in early acute rejection rates would lead to im-
provements in long-term graft survival (5). This led investi-
gators to postulate that early acute rejection could predict
long-term graft survival (1,4). From the era of 1988 until
were improving (6), lending support for this postulate.
On the other hand, new therapeutic regimens, while reduc-
ing the incidence of acute rejection, have often times failed
to show a significant beneficial effect on long-term graft
survival. In some cases this may be owing to trials pow-
ered to show a statistically significant difference in acute
rejection rates but not adequately powered for the rarer
and later end point of graft survival.
Numerous groups have attempted to develop clinical and
histopathological criteria to further characterize the relation
between acute rejection and graft survival (7–9). In most
clinical trials, acute rejection rates, histological grades and
steroid responsiveness are reported, while response to
therapy in terms of functional recovery is usually not re-
ported. In 1972, Silcott et al. reported that of those renal
allografts ‘which were unable to return the serum creati-
nine value to within 20% of the pre rejection levels, 93%
ultimately failed and 47% of the patients died’, compared
with a failure rate of 27% in patients with acute rejection
but no loss of function within 20%. More recent studies
reemphasize the concept that acute rejection might not
have any deleterious effect on long-term graft survival pro-
vided complete functional recovery is achieved (10,11).
With the present study, we first determined trends in
acute rejection rates and long-term graft survival and sub-
sequently proceeded to investigate whether continued im-
provements in acute rejection rates have translated into
improved graft survival.
Methods
We examined all 62 103 first solitary adult (age > 17 years) transplant re-
cipients included in the Scientific Registry of Transplant Recipients (SRTR)
database transplanted between 1995 and 2000. The year of transplant was
considered the main variable of interest to ascertain the change in outcomes
of graft survival, death-censored graft survival, and patient survival over the
modern era. We constructed univariate models for these outcomes by year

of transplantation. We then generated models to quantify the impact of the
year of transplant for those recipients with a minimum 1-year follow up.
Subsequently, we analyzed the effect of transplantation year separately by
the presence of acute rejection within the first 6 months of transplant. To
examine the impact of year of transplantation in conjunction with donor
type (deceased donor or living), we utilized an interaction model in which
groupings were created for each year and donor type combination.
We measured the impact of renal function in the presence and absence of
acute rejection, analyzing 38 426 adult first transplant recipients from 1995
to 2001 from the SRTR database. We excluded recipients with less than
1 year of follow up or missing values of creatinine in the 6- and 12-month
post-transplantation intervals from the analysis. We then took a subset of
patients that had no acute rejection indicated within the first 6 months
of follow up and used their creatinine levels at 6 months and 12 months
as an indication of renal function. We recorded acute rejection incidents
for patients that had indications of treatment for acute rejection on their
follow-up forms. Patients were followed until graft loss, death, or their last
patient follow-up date as indicated in the registry.
We verified results by repeating analyses using (serum creatinine)−1 ,
glomerular filtration rate (GFR) as calculated both by Cockcroft Gault (12)
(adjusted for body surface area), and the modification of diet in renal disease
(MDRD) (13) formulae as measures of renal function. Calculations incorpo-
rating weight and height utilized imputed values. Our models incorporated
imputed values of weight and height, using nonmissing values of these
measurements along with age as predictors stratified by race and gender.
Baseline renal function measures were calculated at 6 months and com-
pared with levels at 12 months post-transplant follow up. We considered
return to baseline for patients with at least 95% renal function at 12 months
as they had at 6 months; this level of baseline function was conceived to
account for some degree of measurement error and intrapatient variability.
We compared outcomes of patient survival, death-censored graft survival,
and overall graft survival for those who did not have acute rejection in the
first 12 months, those who did not have acute rejection in the first 6 months
but did between 6 and 12 months and returned to baseline renal function
level, and those without acute rejection in their first 6 months and had acute
rejection between 6 and 12 months but failed to return to baseline level of
renal function. In subsequent analyses, groupings for patients with acute
rejection and who failed to return to baseline were further delineated into
85–95% baseline function, 75–85% baseline function, and <75% baseline
function to measure the relative impact on the hazard of outcomes with
more serious gradients of renal function reduction. Subsets of the patient
population were also separately analyzed to assess if the trends for out-
comes remained consis ent.
Outcomes were measured with univariate Kaplan-Meier models and over-
all strata comparisons measured by log-rank tests. Multivariate Cox pro-
portional hazard models were used to assess risk for groupings and adjust
for potential confounding factors. Cox models were corrected for induction
regimen, antiproliferative regimen, calcineurin inhibitor, cold ischemia time,
PRA level, HLA mismatches (separated into A, B and DR), donor and re-
cipient age, gender, and race, presence of delayed graft function, donation
type, and primary diagnosis of recipient. Proportional hazard assumptions
were tested by visually assessing log-log survival curves. Medication regi-
mens were considered solely on an intent-to-treat basis, without regard to
changes after the initial transplant period. We tested for linear trends for
demographic characteristics over the years of transplant with the Cochran-
Armitage trend test. The Efron method was used to handle tied outcome
occurrences. All analyses were conducted on SAS software (v. 8.02, Cary,
NC) and a type one error probability of 0.05 was utilized as an indication of
statistical significance.
American Journal of Transplantation 2004; 4: 378–383
Lack of Improvement in Renal Allograft Survival
Results
Demographic information by year of transplantation by do-
nation type is displayed in Tables 1. We demonstrated
over the study period, a significant linear positive trend for
2-HLA-A,B and DR mismatches, waiting time on dialysis
greater than 24 months, diabetes as primary diagnosis, re-
cipients older than 65 years, unrelated donations, and med-
ications at baseline including MMF, Neoral, Prograf, generic
cyclosporine, IL-2 induction, and Thymoglobulin for the liv-
ing transplant population. Significant negative trends in the
living population existed for patients with PRA > 30 and
for medications at baseline including AZA, cyclosporine,
OKT3, and ATG.
The 2-year survival estimates from univariate analy-
ses for overall graft survival by donation type for re-
cipients with and without indications of acute rejec-
tion within 6 months of transplant are displayed in
Table 2. The rates of early and late acute rejection
episodes are displayed in Figure 1; rates showed a
strong decline after 1996 in the follow-up periods that we
examined.
Cox model hazard estimates and 95% confidence intervals
adjusted for covariates for the outcome of overall graft loss
for deceased donor transplants 1995–2000 demonstrated
a slight elevation in risk, while living transplants seemed to
be rather flat in terms of risk estimates by year of transplant
(displayed in Figure 2). As displayed in Figure 3, death-
censored graft loss hazard estimates for the 1995–2000
period seem to suggest an increased risk in more recent
years for both cadaveric and living transplants. We also ex-
amined the outcome of patient death; hazard estimates
for this outcome for deceased donor transplant subset for
1996–2000 (with 1995 as reference) were 0.994 (0.902,
1.095), 1.134 (1.019 1.262), 0.984 (0.876, 1.105), 1.077
(0.952, 1.219), and 1.103 (0.963, 1.264). Living transplants’
relative risks for 1995–2000 with the same reference group
(cadaveric transplant 1995) were 0.752 (0.653, 0.865),
0.710 (0.606, 0.832), 0.740 (0.625, 0.876), 0.770 (0.646,
0.917), 0.660 (0.542, 0.803), and 0.660 (0.537, 0.810),
respectively.
To examine the impact of acute rejection, we analyzed
outcomes of those who experienced no acute rejection
in the 6–12-month period post transplant, those who ex-
perienced acute rejection and returned to baseline renal
function, and those who experienced acute rejection and
failed to return to baseline. Utilizing (serum creatinine)−1 as
the measure of renal function, 53.9% of patients returned
to their 6-month baseline renal function level (1237/2296)
at 12 months. This return rate depicted a negative trend by
year of transplant, as displayed in Table 3, peaking in 1996
at 68.4% and dipping to 40.6% in 2000. This linear trend
towards a reduced rate of returning to baseline was statis-
tically significant as tested by the Cochran-Armitage trend
379
Meier-Kriesche et al.

Table 1: Demographic information by year of transplant

Year

1995 1996 1997 1998 1999 2000 Trend test1 (direction)

Living transplants
2 HLA-A MM percentage 10.5 12.8 12.8 15.5 16.1 18.3 Positive
2 HLA-B MM percentage 15.7 18.8 19.3 22.0 23.1 26.0 Positive
2 HLA-DR MM percentage 10.6 12.9 13.5 15.0 15.0 18.5 Positive
PRA ≥ 30% 8.2 7.3 6.7 6.3 6.1 6.7 Negative
Donor Age > 55% 8.4 8.4 9.4 9.8 8.9 9.1 None
Recipient Age > 65% 3.6 4.2 4.3 5.0 5.4 7.1 Positive
Waiting time on dialysis 24 months +% 15.8 16.2 15.8 15.5 15.7 16.3 None
AA Donor percentage 13.6 12.8 13.5 12.8 14.9 12.9 None
AA Recipient percentage 14.4 14.4 14.0 14.1 16.0 13.8 None
Diabetes as primary disease percentage 16.4 14.7 12.4 13.4 16.6 17.4 Positive
Hypertension as primary disease percentage 10.2 11.5 12.9 11.7 11.5 11.7 None
MMF percentage 10.1 44.4 61.9 70.9 77.0 71.7 Positive
AZA percentage 71.7 32.8 21.2 12.4 7.9 5.3 Negative
Neoral percentage 4.0 55.8 69.0 61.2 56.4 46.1 Positive
Prograf percentage 3.3 7.4 12.6 23.4 28.4 37.7 Positive
Cyclosporine percentage 79.8 17.1 7.5 4.9 3.9 2.9 Negative
Generic cyclosporine percentage 0.0 0.0 0.1 0.1 0.4 1.3 Positive
IL2% 0.3 1.1 0.1 12.4 26.6 34.8 Positive
Thymoglobulin percentage 0.0 0.0 0.0 0.2 2.9 5.5 Positive
OKT3% 18.6 14.0 11.1 6.9 3.2 2.2 Negative
ATG percentage 1.7 11.0 12.1 8.5 4.8 2.5 Negative
Unrelated donation percentage 13.5 15.9 17.2 20.2 22.2 27.0 Positive
Deceased donor transplants
2 HLA-A MM percentage 40.8 41.5 42.9 40.6 41.1 42.1 None
2 HLA-B MM percentage 36.0 36.8 38.1 37.3 39.2 41.4 Positive
2 HLA-DR MM percentage 18.5 19.4 21.0 20.8 22.9 22.8 Positive
PRA ≥ 30% 14.5 15.1 14.9 13.8 15.2 15.7 None
Donor Age > 55% 14.3 16.1 16.7 16.6 17.0 16.8 Positive
Recipient Age > 65% 7.2 8.1 8.3 10.0 10.1 12.2 Positive
Waiting time on dialysis 24 months +% 48.6 51.0 53.8 54.0 53.9 54.9 Positive
AA donor percentage 11.3 11.3 11.1 11.3 10.2 10.2 Negative
AA recipient percentage 27.3 27.5 28.4 27.8 28.1 29.7 Positive
Diabetes as primary disease percentage 10.8 10.4 10.3 10.4 13.0 15.7 Positive
Hypertension as primary disease percentage 15.5 16.6 18.2 17.8 17.7 18.4 Positive
Cold ischemia time > 24 h percentage 37.7 36.2 31.6 31.4 28.3 25.3 Negative
MMF percentage 10.2 42.8 62.5 68.4 74.8 72.4 Positive
AZA percentage 71.3 30.9 18.8 10.9 6.9 4.5 Negative
Neoral percentage 2.1 50.9 64.5 59.8 49.8 43.5 Positive
Prograf percentage 5.2 11.4 17.4 22.8 30.1 39.8 Positive
Cyclosporine percentage 79.9 16.0 6.5 4.7 5.4 2.3 Negative
Generic cyclosporine percentage 0.0 0.0 0.0 0.2 0.4 0.8 Positive
IL2% 0.3 1.0 0.2 11.4 30.7 41.0 Positive
Thymoglobulin percentage 0.0 0.0 0.0 0.4 6.2 12.8 Positive
OKT3% 32.8 28.0 23.8 14.2 5.7 2.9 Negative
ATG percentage 1.4 16.7 20.1 14.8 8.0 3.6 Negative
1 Cochran-Armitage trend test: indications for significant trends (a < 0.05 for two-sided test) over year of transplant.

test (p < 0.001). The acute rejection rates for the entire
follow-up periods that we investigated indicated later acute
rejection rates were consistently higher in the group that
had initially displayed acute rejection in the second 6-month
post-transplant follow-up period. The rate of rejection in
the second year post-transplant for the no acute rejection
group was 5.7%, for the return to baseline group 16.3%,
and for the fail to return to baseline group 27.7%. In a sim-
ilar fashion, during the third year post transplant the rejec-
tion rates were 3.5% for the no acute rejection group, 6.4%
for the return to baseline group, and 11.3% for the fail to
return to baseline. Rates in the fourth year post-transplant
followed the same pattern; for the no acute rejection group
the rate of acute rejection was 3.0%, for the return to base-
line group 5.0%, and for the failure to return to baseline
group 8.1%.

380 American Journal of Transplantation 2004; 4: 378–383

 Lack of Improvement in Renal Allograft Survival

Table 2: Two-tier univariate overall graft survival rates for recip- 1.2 1.1 4
ients with and without indications of acute rejection within 6 1.10 1. 09 1.09
1.1
months post-transplant by donation type 1.2
Relative 1 1.00
Risk 1.00 1.03
No indication of acute rejection Acute rejection 0.9 1.1
0.9 7
0.8 0.9 6 0.9 4 1
Year of Deceased Deceased 0.89
0.7
transplant donor Living donor Living 0.88 0.9

1995 91.3 95.5 90.2 93.9 Deceased Donor 0.8

Transplants
1996 91.3 95.3 90.4 94.2 0.7
1997 91.5 96.0 91.0 94.6 2000
Living Transplants 1999
1998 92.1 95.6 90.7 94.9 1997
1998
1996
1999 91.5 94.9 90.7 95.7 1995 Year of Transplant
2000 88.9 93.8 89.0 95.6
Recipients utilized in calculations had a minimum 6-month follow-
up period. Figure 3: Relative risk for death-censored graft loss by donor
type. Model corrected for induction, antiproliferative, and inhibitor
43.7 medication regiments at baseline, cold ischemia time, PRA level,
35.7
40
HLA-A, -B, and -DR mismatches, recipient and donor gender, eth-
33.9 40
35 27.4 35 nicity, age, presence of delayed graft function, primary diagnosis,
30
22.5
21.4 30 % and waiting time on dialysis.
25 17.9 25 AR
20 15.3 20
14.6
15
7.2
15 Table 3: Rate of return to baseline function after acute rejection
10 10
6.1 6.7
7.4 5 by era
5 6.1
0 5.8 6 0
5.2
Year of Return to No return Rate of
1995 0−6 months
1996 transplant baseline to baseline return
1997 2.9 6−12 months
1998 1995 292 245 54.4%
1999 1996 561 259 68.4%
12−24 months
2000
1997 86 149 36.6%
1998 99 139 41.6%
Figure 1: Incidence of early and late acute rejection episodes 1999 116 144 44.6%
by era. Indications of rejection are not independent; patients may 2000 69 101 40.6%
have contributed repeated episodes of rejection in different follow- 2001 14 22 38.9%
up periods. Total 1237 1059 53.9%

1.2
Return to baseline function estimated by 1/Scr.
1.1 4
1.1 1
1.1 2 Significant linear trend (p < 0.001) towards no return to baseline
1.1
1.04
Relative 1.2 as tested by the Cochran-Armitage trend test.
Risk 1 1.00 0.99
0.9 1.1

0.8 1
0.7 0.8 5 0.8 4
0.79 0.9 unadjusted rates were 74.4%, 72.7%, and 50.4%, with
0.8 3 0.8 1
Deceased Donor
Transplants
0.8 2
0.8
an overall test for equality of strata being highly signifi-
cant also (p < 0.0001), when testing the model with the
0.7

Living
Transplants 1997
1996
1995
Figure 2: Relative risk for overall graft loss by donor type.
Model corrected for induction, antiproliferative, and inhibitor med-
ication regiments at baseline, cold ischemia time, PRA level, HLA-
A, -B, and -DR mismatches, recipient and donor gender, ethnicity,
and age, presence of delayed graft function, primary diagnosis,
and waiting time on dialysis.
We analyzed the impact of the acute rejection/renal func-
tion groupings on overall graft survival. Examining the out-
comes for the three group designations (no acute rejection,
rejection with return to baseline, and rejection without re-
turn to baseline) utilizing Cockcroft-Gault as an estimate
of GFR yield 3-year-unadjusted survival rates of 91.5%,
91.1%, and 72.1%, respectively, (see Table 4). The 6-year
1999
2000 first two strata only, there was no significant difference be-
1998
tween the groups with no acute rejection and with acute
Year of Transplant
rejection and return to baseline (p = 0.5289). Subsequently,
we examined the results using the MDRD estimate of GFR
and (serum creatinine)−1 and found very similar results. We
also analyzed the overall graft survival by use of five acute
rejection/renal function levels (no acute rejection, acute re-
jection and return to baseline, acute rejection and a return
to 85–95% renal function, acute rejection and return to 75–
85% renal function, and acute rejection and a return to less
than 75% renal function). The 6-year overall unadjusted
graft survival rates by functional status after rejection as
measured by Cockcroft-Gault as an estimate for GFR were
74.4%, 72.7%, 67.0%, 50.2%, 38.0% (see Figure 4), re-
spectively.
We were also interested in measuring the death-censored
graft survival for the same grouping levels. Utilizing the

American Journal of Transplantation 2004; 4: 378–383 381

Meier-Kriesche et al.
Table 4: Unadjusted overall graft survival by acute rejection/renal
function group
3-year overall 6-year overall
Group graft survival graft survival
No acute rejection 91.5 74.4
Acute rejection and return 91.1 72.7
to baseline
Acute rejection and fail to 72.1 50.4
return to baseline
Figure 4: Kaplan-Meier plot of overall graft survival by acute
rejection/glomerular filtration rate grouping levels.
five grouping levels as stated previously and Cockcroft-
Gault estimated GFR as the measure of renal function the
6-year death-censored survival rates were 84.7%, 82.3%,
77.6%, 60.1%, 45.1%, respectively. After adjusting for the
relevant covariates in a Cox model, patients with acute re-
jection but functional recovery to within 5% from base-
line function had a relative risk of 1.046 (0.859, 1.273)
for death-censored graft failure and those who failed to
reach baseline following acute rejection had a relative risk
of 3.077 (2.691, 3.519) for death-censored graft loss when
compared with patients without acute rejection. For the
five renal function groupings following acute rejection, with
the no acute rejection group as the reference, the risk es-
timates were 1.067 (0.882, 1.291), 1.223 (0.874, 1.713),
2.739 (2.024, 3.705), and 5.130 (4.332, 6.076) (displayed
in Table 5). To confirm our findings were applicable in par-
ticular substrata, we repeated this portion of the analysis
by donor type, racial subsets, and for patients classified
by initial GFR function; the results were similar for each of
these.
Discussion
As immunosuppressive regimens have evolved, acute
rejection rates have progressively decreased after renal
transplantation. In addition, both short and long-term graft
survival had been improving from the period of 1988 un-
til 1996 (6). The data presented in our study suggest that
this improvement in graft survival has not continued in the
period of 1995–2000. Overall graft survival and patient sur-
vival have remained unchanged since 1995, while death-
382
censored graft survival shows a significant decrease in
the same time period. This lack of improvement has been
shown in the setting of an almost halving of early and late
acute rejection rates during the same time period. This po-
tential discordance between trends in acute rejection rates
and trends in long-term graft survival has been observed
in several recent clinical trials.
Acute rejection has been used in many studies as the pri-
mary endpoint, under the assumption that reduced acute
rejection rates would ultimately lead to better graft survival.
The data analyzed here would question this assumption
and furthermore would imply that the achievement of ever
lower rejection rates does not necessarily lead to improved
graft survival.
A partial explantation of this apparent paradox is that not all
acute rejections are the same. In fact, our data reempha-
sizes the idea that the functional response of the acute re-
jection episode to therapy is important in distinguishing be-
tween rejection episodes impacting graft survival vs. those
that do not. In fact, rejection episodes that did not affect
renal function did not seem to have any impact on graft
survival. The profound impact of acute rejection episodes
that do not return to a functional baseline, on graft sur-
vival, could be in part result from the immediate structural
damage the rejection episode inflicts on the graft. Addi-
tionally, acute rejection episodes that do not respond well
to treatment are possible markers for an increased risk for
subsequent late rejection. In fact, in our data the repeat
acute rejection rate was higher in patients with primary re-
jection who did not return to baseline, and the poor graft
survival rate was probably accentuated by this.
Our study indicated that since 1995 there has been a trend
towards fewer rejections returning to baseline function af-
ter treatment. That might in fact be part of the observed
discordance between rejection rates and graft survival. It
is possible that many of the acute rejection episodes that
were less severe in terms of effects on functional status
are those that were reduced in the more recent era while
rejections with stronger functional impact persisted. Pre-
vious registry analysis had suggested that in recent era
acute rejection episodes had a stronger impact on long-
term graft survival potentially secondary to a dispropor-
tionate in milder rejection episodes (14). However, it is un-
likely that this finding can completely account for the lack
of correlation between reduction in acute rejection rates
and trend in graft survival. Other potential reasons might
include transplantation of higher risk donors and recipients
in more recent years (note that an attempt was made to
correct for this in the multivariate analysis).
Additionally, other factors affecting graft survival might be
changing over time. It is conceivable that while acute re-
jection is becoming less frequent with more efficacious
immunosuppression, the effects of over immunosuppres-
sion, like polyomavirus, are becoming more frequent. It
American Journal of Transplantation 2004; 4: 378–383

Table 5: Multivariate risk estimates for death-censored graft survival by acute rejection status and functional return to baseline
Acute rejection and return to functional baseline group
No acute rejection
Acute rejection and return to within 95% of baseline
Acute rejection and return to within 85–95% of baseline
Acute rejection and return to within 75–85% of baseline
Acute rejection and return to within < 75% of baseline
Return to baseline function estimated by calculated creatinine clearance (Cockroft-Gault).
is likely that maintenance immunosuppression has also
changed during this time period, particularly given the re-
cent emphasis on immunosuppression minimization and
withdrawal trials.
In summary, despite impressive reductions in acute rejec-
tion rates since 1995, the favorable trend in graft survival
observed in previous years has not continued during the
same time period. Changes in acute rejection rates do not
seem to reliably correlate with the later end point of graft
loss. However, as the risk for graft loss is different be-
tween acute rejections that lead to functional deterioration
as opposed to those that do not, this distinction should
be reported when novel therapeutic regimens are studied.
The reason for the lack of graft survival improvements in
more recent era needs to be investigated in more detail.
In this era of more novel therapies, some caution may be
needed in extrapolating improvements in intermediate end
points and improvements in long-term outcomes.
Acknowledgments
The data reported here were supplied by the U.S. Scientific Renal Trans-
plant Registry (SRTR). The interpretation and reporting of these data are
the responsibility of the authors and in no way represent an official policy
or interpretation of the U.S. Government.
Part of this data was presented at the annual meeting of the American
Society of Transplantation in Washington 2003.
We would like to express our appreciation to Suzanne C. Johnson who has
helped with the editing and reviewing of the paper.
References
1. Tesi RJ, Elkhammas EA, Henry ML, Davies EA, Salazar A, Fer-
guson RM. Acute rejection episodes. best predictor of long-term
primary cadaveric renal transplant survival. Transplant Proc 1993;
25: 901–902.
American Journal of Transplantation 2004; 4: 378–383
Lack of Improvement in Renal Allograft Survival
Reference group
Hazard Confidence interval
1.067 (0.882, 1.291)
1.223 (0.874, 1.713)
2.739 (2.024, 3.705)
5.130 (4.332, 6.076)
2. Pirsch JD, Ploeg RJ, Gange S et al. Determinants of graft survival
after renal transplantation. Transplantation 1996; 61: 1581–1586.
3. Almond PS, Matas A, Gillingham K et al. Risk factors for chronic
rejection in renal allograft recipients. Transplantation 1993; 55:
752–756.
4. Ferguson RM. Acute rejection episodes – Best predictor of long-
term primary cadaveric renal transplant survival. Clin Transplant
1994; 8: 328–331.
5. Flechner SM, Modlin CS, Serrano DP et al. Determinants of
chronic renal allograft rejection in cyclosporine-treated recipients.
Transplantation 1996; 62: 1235–1241.
6. Hariharan S, Johnson CP, Bresnahan BA, Taranto SE, McIntosh
MJ, Stablein D. Improved graft survival after renal transplantation
in the United States, 1988–96. N Engl J Med 2000; 342: 605–612.
7. McKenna R, Stern E, Jeffery J, Ru DN. Computerized image anal-
ysis of Sirius Red-stained renal allograft biopsies as a surrogate
marker to predict long-term allograft function.J Am Soc Nephrol
2003; 14: 1662–1668.
8. Haas M, Kraus ES, Samaniego-Picota M, Racusen LC, Ni W, Eu-
stace JA. Acute renal allograft rejection with intimal arteritis: his-
tologic predictors of response to therapy and graft survival. Kidney
Int 2002; 61: 1516–1526.
9. Takeuchi K, Tei K, Mannami M, Toshino A, Oka A, Ohoka H, Ito
H. Histopathology of a human allografted kidney with clinically
sufficient function. Clin Transplant 2000; 14: 25–29.
10. Vereerstraeten P, Abramowicz D, de Pauw L, Kinnaert P. Absence
of deleterious effect on long-term kidney graft survival of rejec-
tion episodes with complete functional recovery. Transplantation
1997; 63: 1739–1743.
11. Madden RL, Mulhern JG, Benedetto BJ et al. Completely re-
versed acute rejection is not a significant risk factor for the devel-
opment of chronic rejection in renal allograft recipients. Transpl
Int 2000; 13: 344–350.
12. Cockcroft DW, Gault MH. Prediction of creatinine clearance from
serum creatinine. Nephron 1976; 16: 31–41.
13. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A
more accurate method to estimate glomerular filtration rate from
serum creatinine: a new prediction equation. Modification of Diet
in Renal Disease Study Group. Ann Intern Med 1999; 130: 461–
470.
14. Meier-Kriesche HU, Ojo AO, Hanson JA et al. Increased impact
of acute rejection on chronic allograft failure in recent era. Trans-
plantation 2000; 70: 1098–1100.
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