CLINICAL RESEARCH www.jasn.

org

Early Steroid Withdrawal in Deceased-Donor Kidney

Transplant Recipients with Delayed Graft Function
Sunjae Bae,1,2,3 Jacqueline M. Garonzik Wang,2 Allan B. Massie,1,2 Kyle R. Jackson ,2
Mara A. McAdams-DeMarco ,1,2 Daniel C. Brennan,4 Krista L. Lentine,5
Josef Coresh ,1,3,4 and Dorry L. Segev 1,2
Departments of 1Epidemiology and 3Biostatistics, Johns Hopkins School of Public Health, Baltimore, Maryland;
Departments of 2Surgery and 4Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland; and
5
Center for Abdominal Transplantation, Saint Louis University, St. Louis, Missouri

ABSTRACT
Background Early steroid withdrawal (ESW) is associated with acceptable outcomes in kidney transplant
(KT) recipients. Recipients with delayed graft function (DGF), however, often have a suboptimal allograft
milieu, which may alter the risk/benefit equation for ESW. This may contribute to varying practices across
transplant centers.
Methods Using the Scientific Registry of Transplant Recipients, we studied 110,019 adult deceased-donor KT
recipients between 2005 and 2017. We characterized the association of DGF with the use of ESW versus con-
tinued steroid maintenance across KT centers, and quantified the association of ESW with acute rejection,
graft failure, and mortality using multivariable logistic and Cox regression with DGF-ESW interaction terms.
Results Overall 29.2% of KT recipients underwent ESW. Recipients with DGF had lower odds of
ESW (aOR=0.600.670.75). The strength of this association varied across 261 KT centers, with center-
specific aOR of ,0.5 at 31 (11.9%) and .1.0 at 22 (8.4%) centers. ESW was associated with benefits and harms
among recipients with immediate graft function (IGF), but only with harms among recipients with DGF. ESW
was associated with increased acute rejection (aOR=1.09 1.161.23), slightly increased graft failure
(aHR=1.011.061.12), but decreased mortality (aHR=0.860.890.93) among recipients with IGF. Among recipients
with DGF, ESW was associated with a similar increase in rejection (aOR51.12; 95% CI, 1.02 to 1.23), a more
pronounced increase in graft failure (aHR51.16; 95% CI, 1.08 to 1.26), and no improvement in mortality
(aHR51.00; 95% CI, 0.94 to 1.07). DGF-ESW interaction was statistically significant for graft failure
(P50.04) and mortality (P50.003), but not for rejection (P50.6).
Conclusions KT centers in the United States use ESW inconsistently in recipients with DGF. Our findings
suggest ESW may lead to worse KT outcomes in recipients with DGF.

JASN 31: 175–185, 2020. doi: https://doi.org/10.1681/ASN.2019040416

Approximately 30% of deceased-donor kidney characteristics of individual KT recipients. In

transplant (KT) recipients in the United States un- particular, ESW may not achieve sufficient
dergo early steroid withdrawal (ESW), a mainte-
nance immunosuppression protocol that aims to
reduce the adverse effects from long-term steroid Received April 24, 2019. Accepted September 10, 2019.

use.1 Previous studies have suggested ESW leads to
no or minimal increases in acute rejection and graft
failure, 2–10 while reducing steroid-related side
effects such as new-onset diabetes, dyslipidemia,
and fracture.11–14 However, this risk/benefit equa-
tion of ESW can be altered by the clinical
Published online ahead of print. Publication date available at
www.jasn.org.
Correspondence: Dr. Dorry L. Segev, Department of Surgery,
Johns Hopkins Medical Institutions, 2000 E Monument Street,
Baltimore, MD 21205. Email: dorry@jhmi.edu
Copyright © 2020 by the American Society of Nephrology

JASN 31: 175–185, 2020 ISSN : 1046-6673/3101-175 175

 CLINICAL RESEARCH www.jasn.org
immunosuppression in certain subgroups, especially those
with higher immunologic risk.15
One subgroup that might be unsuitable for ESWis recipients
who develop delayed graft function (DGF). DGF is often a con-
sequence of a suboptimal allograft milieu, which subsequently
increases the risk of acute rejection and graft failure.16–19 This
milieu may necessitate potent immunosuppression regimens
that could also counterbalance the increased risks of acute re-
jection and graft failure,20 lending support to the use of con-
tinued steroid maintenance (CSM) over ESW in recipients
with DGF. Alternatively, given that DGF is often attributable
to ischemia-reperfusion injury rather than immune re-
sponse,16,20,21 the pathophysiology of DGF may have little
interaction with the pathway through which immunosuppres-
sion influences KT outcomes. In other words, DGF may not
indicate high “immunologic” risk in the context of individ-
ualizing steroid use, despite being a risk factor for rejection
and graft failure. There is no clinical evidence to support
either ESW or CSM in the context of DGF. This knowledge
gap may have negative implications for post-KT manage-
ment, given that DGF is a common condition with an in-
cidence of 25%–36% among recipients of deceased-donor
KTs.17,22
In this nationwide study, we sought to understand whether
DGF manifests a suboptimal allograft milieu in which ESW is
not desirable for maintenance immunosuppression after KT.
We first described the current practice by quantifying the
association between DGF and the use of ESW (versus
CSM) at each KT center across the country. We then inves-
tigated whether the association between ESW and post-KT
outcomes varies by DGF status using interaction term
analyses.
METHODS
Data Source
This study used data from the Scientific Registry of Trans-
plant Recipients (SRTR). The SRTR data system includes
data on all donors, wait-listed candidates, and transplant
recipients in the United States, which are submitted by the
members of the Organ Procurement and Transplantation
Network (OPTN). The Health Resources and Services
Administration, US Department of Health and Human
Services, provides oversight to the activities of the OPTN
and SRTR contractors.
Study Population
Using the SRTR data, we studied adult (.18 years) recipients of
deceased-donor kidney-alone transplants from January 1, 2005
to December 31, 2017 who received post-transplant mainte-
nance immunosuppression using tacrolimus and mycopheno-
late. Recipients whose immunosuppression records (n=2285,
2.0%) or DGF status (n=13, 0.01%) could not be retrieved, and
those who received maintenance agents other than tacrolimus
176 JASN
Significance Statement
Early steroid withdrawal (ESW) is a maintenance immunosuppres-
sion strategy to avoid the sequelae of long-term steroid use in kidney
transplant (KT) recipients. Recipients with delayed graft function
(DGF) may have a suboptimal allograft milieu, which may alter the
risk/benefit equation of ESW. In this nationwide study, the authors
found use of ESW in recipients with DGF varied at United States
transplant centers. The authors also identified differences in out-
comes after ESW in patients with and without DGF. Among recip-
ients with immediate graft function, ESW was associated with
possible harms such as increased rejection and benefits such as
decreased mortality. However, among recipients with DGF, ESW
was associated only with possible harms, including increased acute
rejection and graft failure. Recipients with DGF also saw no change
mortality with ESW. Our findings suggest ESW is harmful in KT re-
cipients with DGF.
and mycophenolate (n=16,188, 12.8%) were excluded.
DGF was defined as the need for dialysis within the first
week after transplant, as per the United Network for Organ
Sharing/OPTN Kidney Transplant Recipient Registration
form.23 For this reason, we excluded recipients who died or
developed graft failure within 7 days post-KT or discharge
(n=1154, 1.0%). Absence of DGF was termed immediate graft
function (IGF). ESW was defined as withdrawal of mainte-
nance steroid by the time of discharge from the KT admission;
all other recipients were considered CSM. As the exact date of
steroid withdrawal was not included in our data, we excluded
the recipients who were not discharged within 30 days post-KT
(n=1221, 1.1%) to exclude “late” steroid withdrawal cases
(i.e., beyond the first few weeks post-KT) and their CSM coun-
terparts. Our final study population included 110,019 recipients.
Use of ESW
To study nationwide temporal trends in ESWuse, we quantified
the proportion of recipients who underwent ESW by calendar
year of transplant. To study center-level variation in ESW use,
we quantified the proportion of recipients who underwent
ESW at each center. To determine if DGF was associated
with center-level decisions to use ESW, adjusting for recipient
and donor characteristics, we used a multilevel logistic model
that included a random slope term that estimates the associ-
ation between DGF and ESW use at each transplant center.
A large variance in this term indicates a large center-level var-
iation in practice. We fitted this model using a Gibbs sam-
pler with uninformative diffuse priors under the Bayesian
framework.24
ESW and Inverse Probability of Treatment Weights
For KT outcomes analyses (acute rejection, graft survival, and
patient survival), our primary exposure was ESW, as the initial
maintenance immunosuppression regimen, which was treated
as a time-fixed exposure. The time-fixed-exposure approach
aims to estimate the effect of ESW, i.e., that of withdrawing
steroid from the initial maintenance regimen, and does not
require additional assumptions. This design is analogous to
JASN 31: 175–185, 2020

the intention-to-treat approach in clinical trials.25 In addition,
reinitiations or late steroid withdrawals are often related to
rejection or steroid-associated side effects, which can be re-
garded as mediators between the initial treatment assign-
ment and the outcomes of interest under our conceptual
framework.
When studying KT outcomes, we used the inverse proba-
bility of treatment weights (IPTW) to control for confounders,
and confounding by indication (differences between the recip-
ients that might have influenced the decision for ESW). The
propensity score for undergoing ESW (psESW) was estimated
using a generalized estimating equation with logistic link
to account for clustering at transplant centers (Supplemental
Table 1). Based on the SRTR Risk Adjustment Model, we ad-
justed for recipient factors (age, race, sex, panel-reactive anti-
gen [PRA], previous transplants, body mass index, diabetes,
hypertension, cause of ESKD, pre-emptive transplant, time on
dialysis, serum albumin, symptomatic peripheral vascular dis-
eases, previous malignancy, hepatitis B and C infection, edu-
cation level, and primary payer), donor factors (age, race, sex,
body mass index, hepatitis C infection, donation after cardiac
death, diabetes, hypertension, stroke as the cause of death,
donor pulsatile perfusion, and terminal serum creatinine),
and transplant factors (HLA-A/-B/-DR mismatches, cold is-
chemic time, and induction immunosuppression agent).
1 1
IPTW was derived as psESW for the ESW group and 1 2 psESW
for the CSM group. We examined the distribution of the IPTW
values to detect any observations with extremely large weights
and found none.
Acute Rejection
The OPTN queries centers for information on acute rejec-
tion according to periods covered by specific reporting forms
(0–6 and 7–12 months, then annual periods), but exact dates
of acute rejection within reporting periods are not collected.
We defined acute rejection from SRTR records according to
center reports of an acute rejection event occurring in a re-
porting period, as per prior methods for identifying acute re-
jection from United States registry data.26,27 For this reason,
we studied acute rejection during the first year post-KT as a
binary outcome. We conducted logistic regression to com-
pare the odds of acute rejection between the ESW and CSM
groups. We weighted the recipients using the IPTW de-
scribed above to account for differences in recipient, donor,
and transplant factors. We included an interaction term for
DGF and ESW to test whether the association of ESW (versus
CSM) with acute rejection varied in recipients with DGF
versus IGF.
Graft and Patient Survival
Graft survival was defined as the time from transplant to graft
failure, censoring for death. Patient survival was defined as the
time from transplant to death. The date and cause of death were
ascertained from multiple sources, including follow-up reports
from transplant centers, Centers for Medicare and Medicaid
JASN 31: 175–185, 2020
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Services ESRD Death Notification Form (CMS 2746), and the
Social Security Death Master File. For both outcomes, all re-
cipients were censored at the end of study on December 31,
2017. Unlike acute rejection, we had the exact dates of graft
failure and patient death for all recipients until the end of the
study. The median length of follow-up was 4.2 years for graft
failure and 4.7 years for death. We conducted Cox proportional
hazard regression to compare the hazards of graft failure
and death between the ESW and CSM groups. As with the
rejection analysis, we weighted the recipients using the IPTW
described above to account for differences in recipient,
donor, and transplant factors, and we included an interaction
term for DGF and ESW to test whether the association of
ESW (versus CSM) with graft loss and death varied in recip-
ients with DGF versus IGF.
Cause-Specific Mortality and Stratified Analyses
We conducted additional analyses to explore the potential
mechanisms of the DGF-ESW interaction. First, we compared
the cause-specific hazards of death between ESW and CSM
groups to examine if the DGF-ESW interaction is primarily
driven by any specific pathophysiology. We conducted Cox
proportional hazard regression with IPTW weighting, treating
death due to other causes as censoring events.28 We separately
analyzed death due to cardiovascular diseases (including
stroke), infection, malignancy, and all other causes. Second,
we conducted stratified analysis by recipient age (19–64 versus
$65 years), year of transplant (2005–2011 versus 2012–2017),
induction immunosuppression agent (anti-thymocyte globu-
lin, IL-2 receptor antagonists, alemtuzumab, none, and others),29
immune sensitivity as measured in peak PRA (0–9, 10–79, and
80–100), donation after cardiac death, and the number of
HLA-A/-B/-DR mismatches.
Statistical Analysis
All analyses were performed using Stata 15.1/MP for Linux
(College Station, TX) and R version 3.4. Confidence intervals
are reported as per the method of Louis and Zeger.
RESULTS
Study Population
Among the 110,019 recipients included in the study sample,
27,608 (25.1%) developed DGF, of whom 7083 underwent
ESWand 20,525 underwent CSM. Among the 82,411 recipients
with IGF, 25,032 underwent ESWand 57,379 underwent CSM.
Compared with those with CSM, recipients who underwent
ESW were more likely to be white (48.5% versus 42.3% in IGF;
37.2% versus 32.8% in DGF), have diabetes as the cause of
ESKD (26.8% versus 24.3% in IGF; 35.7% versus 32.1% in
DGF), have lower (less than ten) peak PRA (62.7% versus
52.9% in IGF; 62.9% versus 55.7% in DGF), and were less
likely to have had a previous transplant (8.7% versus 15.0%
in IGF; 9.0% versus 14.3% in DGF) (Table 1).
Steroid and Delayed Graft Function 177
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Table 1. Population characteristics

Characteristics ESW; IGF (n=25,032) CSM; IGF (n=57,379) ESW; DGF (n=7083) CSM; DGF (n=20,525)
Recipient factors
Age (yr) 55 (45, 63) 53 (43, 62) 56 (46, 63) 55 (45, 63)
Female 39.3% 43.8% 29.3% 33.7%
Race
White 48.5% 42.3% 37.2% 32.8%
Black 28.6% 32.3% 35.9% 41.2%
Hispanic/Latino 14.4% 16.6% 17.0% 17.6%
Other/multiracial 8.5% 8.8% 9.9% 8.4%
Preemptive transplant 12.5% 12.1% 2.6% 3.1%
Years on dialysis 3.1 (1.3, 5.3) 3.3 (1.4, 5.5) 4.3 (2.6, 6.3) 4.5 (2.7, 6.8)
Cause of ESKD
GN 20.7% 24.1% 16.7% 19.6%
DM 26.8% 24.3% 35.7% 32.1%
HTN 23.6% 23.3% 23.9% 24.6%
Others 29.0% 28.3% 23.7% 23.7%
Peak PRA
0–9 62.7% 52.9% 62.9% 55.7%
10–79 24.7% 26.2% 25.7% 25.5%
80–100 12.6% 20.9% 11.4% 18.8%
BMI (kg/m2) 27.5 (24.1, 31.6) 27.3 (23.8, 31.2) 28.9 (25.2, 33.0) 28.6 (25.0, 32.7)
Previous transplants 8.7% 15.0% 9.0% 14.3%
HLA mismatches
0 9.8% 10.0% 5.9% 6.9%
1 18.9% 19.2% 17.3% 18.3%
2+ 71.4% 70.8% 76.8% 74.8%
Cold ischemic time (hr) 16.5 (11.2, 23.0) 16.0 (11.0, 21.9) 19.0 (13.0, 25.3) 18.0 (13.0, 24.0)
Donor factors
Age (yr) 39 (25, 51) 38 (24, 50) 44 (31, 53) 44 (30, 53)
Female 40.9% 40.3% 36.6% 37.2%
Race
White 70.8% 66.9% 70.5% 69.1%
Black 14.0% 14.7% 14.0% 13.7%
Hispanic/Latino 12.4% 14.9% 12.4% 13.5%
Other/multiracial 2.8% 3.5% 3.0% 3.7%
Serum creatinine (mg/dl) 0.9 (0.7, 1.3) 0.9 (0.7, 1.2) 1.1 (0.8, 1.6) 1.0 (0.7, 1.5)
DCD 13.0% 12.6% 25.8% 25.6%
ECD 16.4% 14.3% 20.5% 18.3%
Numbers are percentages for categorical variables and median (interquartile range) for continuous variables. DM, diabetes mellitus; HTN, hypertension; BMI, body
mass index; DCD, donation after cardiac death; ECD, expanded criteria donor.

Use of ESW
Overall 29.2% of the recipients underwent ESW. When strat-
ified by DGF status, 25.7% of the recipients with DGF and
30.4% of the recipients with IGF underwent ESW. These pro-
portions, overall (Figure 1A) as well as stratified by DGF status
(Figure 1B), remained relatively stable over the study period.
After adjusting for clinical factors and the variation among
transplant centers, DGF was associated with significantly lower
odds of ESW use (adjusted odds ratio [aOR]=0.600.670.75).
We found a substantial center-level variation in ESW use.
First, the overall tendency to use ESW varied among centers
(Figure 2A). For example, among 261 centers included in
this analysis, 102 (39.1%) centers used ESW in ,5% of their
recipients, whereas 36 (13.8%) used ESW in .75%. Second,
the association between DGF and ESW use also varied
among centers (Figure 2B). After adjusting for clinical
characteristics, recipients with DGF had half the odds of
ESW compared with recipients with IGF (aOR,0.5) at
31 (11.9%) centers, but had higher odds of ESW compared
with recipients with IGF (aOR.1.0) at 22 (8.4%) centers.
Finally, the overall tendency to use ESW (the random inter-
cept term) was not correlated (r=0.07) with the association
between DGF and ESW use (the random slope term): in
other words, how often a center uses ESW did not seem to
be correlated with how strongly DGF was associated with
ESW use at the center.
Acute Rejection, Graft Failure, and Patient Death
The association between ESW and transplant outcomes was
modified by DGF status. Among recipients with IGF, ESW was
significantly associated with increased odds of acute rejection
(aOR=1.091.161.23), a slightly increased hazard of graft failure

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A B
40 40
Recipients with ESW (%)

Recipients with ESW (%)

30 30

20 20

10 10

IGF
0 0 DGF

2005 2008 2011 2014 2017 2005 2008 2011 2014 2017
Year of Transplant Year of Transplant

Figure 1. Stable temporal trends in the use of ESW. (A) Entire population. (B) IGF versus DGF. After adjusting for recipient, donor, and
transplant factors, DGF was associated with significantly lower odds of using ESW (aOR=0.600.670.75).

(adjusted hazard ratio [aHR]=1.011.061.12), and a decreased
hazard of death (aHR=0.860.890.93). In contrast, there was no
beneficial association between ESW and KT outcomes among
recipients with DGF. ESW was associated with increased odds
of acute rejection (aOR=1.021.121.23), an increased hazard of
graft failure (aHR=1.081.161.26), and no difference in the haz-
ard of death (aHR=0.941.001.07) in this subgroup (Table 2)
(Supplemental Figure 1).
Although no interaction was found in the acute rejection
analysis (P=0.6), there was statistically significant interactions
between ESW and DGF in the graft failure (P=0.04) and death
(P=0.003) analyses. In other words, the association of ESW
with acute rejection did not differ by DGF status, whereas
those with graft failure and with death were more adverse
among recipients with DGF than they were among those
with IGF.
Cause-Specific Mortality
In our analyses on cause-specific mortality, DGF modified the
association of ESW with cardiovascular disease–related death,
but not those with infection- or malignancy-related death.
Among the 20,257 deaths included in our study, 3003
(14.8%) were related to cardiovascular disease, 1970 (9.7%)
were related to infection, 1508 (7.4%) were related to malig-
nancy, and 3647 (18.0%) were due to other causes. The re-
maining 10,129 (50.0%) did not have cause of death data in
our records. DGF modified the association between ESW and
cardiovascular disease–related death, with a decreased hazard

A B
100
4
Adjusted Odds Ratio (log scale)

2
Recipients with ESW (%)

75
1.0

50 0.5

0.25
25

0.1

0
Transplant Centers Transplant Centers

Figure 2. Large variation in the use of ESW across transplant centers. (A) Center-specific prevalence of ESW use. (B) Center-specific
aORs for ESW use in recipients with DGF, compared with those with IGF. Each marker indicates a single transplant center. Markers are
sorted along the x axis. (A) The y axis indicates the proportion of the recipients with ESW at the corresponding center. (B) The y axis
indicates the adjusted odds ratio for ESW use in recipients with DGF compared with those with IGF at the corresponding center. The
solid horizontal line indicates the adjusted odds ratio over the entire population (aOR=0.67). The dashed horizontal line indicates no
association (aOR=1.00).

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Table 2. Association between ESW and KT outcomes in
recipients with IGF and with DGF
Outcomes IGF DGF
(ESW versus CSM) (n=82,411) (n=27,608)
Acute rejection (1-yr) 1.091.161.23 1.021.121.23
Death-censored graft 1.011.061.12 1.081.161.26
failure
Death (all cause) 0.860.890.93 0.941.001.07
Death (cause specific)
Cardiovascular 0.740.820.92 0.921.081.26
disease
Infection 0.650.750.86 0.670.821.00
Malignancy 0.860.991.13 0.771.011.31
Others 0.921.011.11 0.911.061.23
Acute rejection was treated as a binary variable at 1 yr post-KT. Other out-
comes were treated as time-to-event variables. The median length of follow-up
was 4.2 yr for graft failure and 4.7 for death. Estimates are aORs for acute re-
jection and aHRs for other outcomes, with 95% CIs in subscripts. A low (,0.05)
interaction P value indicates the association between ESW and the transplant
outcome was significantly different between the IGF and DGF populations.
among recipients with IGF (aHR=0.740.820.92) but not among
those with DGF (aHR=0.921.081.26; interaction P=0.004).
However, the association between ESW and death due to in-
fection, malignancy, or other causes did not vary significantly
between the IGF and DGF recipients (interaction P=0.5,
0.9, and 0.5, respectively) (Table 2).
Stratified Analyses
When stratified by recipient age, we observed the ESW-DGF
interaction in the younger (19–64 years; n=88,248) as well as in
the older ($65 years; n=21,770) recipients. In both sub-
groups, the association of ESW with increased acute rejection
did not vary by DGF status, that with increased graft failure
was more pronounced among recipients with DGF, and
that with decreased death was only observed among recipients
with IGF (Figure 3). Likewise, the ESW-DGF interaction was
similar across the calendar year strata (2005–2011 versus
2012–2017) (Figure 3).
Overall 55,884 (50.8%) recipients received anti-thymocyte
globulin, 18,785 (17.1%) received IL-2 receptor antagonists,
14,375 (13.1%) received alemtuzumab, 14,192 (12.9%) recip-
ients received no induction agent, and 6782 (6.2%) received
others. Our findings on the DGF-ESW interaction were gen-
erally consistent over induction agent strata (Figure 3). How-
ever, the ESW-DGF interaction was slightly different among
those who received IL-2 receptor antagonists for induction. In
this subpopulation, the ESW-DGF interaction on death was
more pronounced (aHR=0.810.911.01 in IGF versus 1.031.231.46
in DGF; interaction P=0.004) and the interaction on acute
rejection, although not statistically significant, appeared
to be in the opposite direction (aOR= 1.07 1.28 1.54 in IGF
versus 0.740.971.28 in DGF; interaction P=0.1).
When stratified by PRA, donation after cardiac death,
and HLA mismatches, the DGF-ESW interactions were overall
consistent over the strata (Figure 3). Nonetheless, the DGF-
ESW interaction on acute rejection was slightly more
pronounced among recipients with zero HLA-DR mis-
match (aOR=0.891.031.20 in IGF versus 1.231.561.98 in DGF;
Interaction interaction P=0.004) (Figure 3A). Similarly, the DGF-ESW
P Value interaction on graft failure was also slightly more pro-
0.6 nounced among those with zero HLA-B mismatch
0.04 (aHR=0.800.951.12 in IGF versus 1.021.351.79 in DGF; interac-
tion P=0.03), and among those with zero HLA-DR mismatch
0.003 (aHR= 0.86 0.97 1.09 in IGF versus 1.02 1.25 1.54 ; interaction
P=0.03) (Figure 3B).
0.004
0.5
DISCUSSION
0.9
0.5
In this nationwide registry analysis, we found that the asso-
ciations between ESW and KToutcomes vary by DGF status.
Among recipients with IGF, ESW was associated with a 6%
increase in the hazard of graft failure, offset by an 11% de-
crease in the hazard of death. However, among recipients
with DGF, ESW was associated with a 16% increase in the
hazard of graft failure and no difference in the hazard of
death. These interactions between ESW and DGF were sta-
tistically significant. Our findings suggest DGF alters the
risk/benefit equation of ESW, such that ESW might possibly
confer a mixture of beneficial and harmful effects among
recipients of KT with IGF, but overall harmful effects among
those with DGF.
Practice patterns regarding ESW among recipients with
DGF were substantially different among transplant centers.
Although DGF was associated with lower odds of ESW use
(aOR= 0.60 0.67 0.75 ) over the entire study population, the
strength of this association varied among transplant centers.
At some centers, recipients with DGF were at lower than half
the odds of undergoing ESW compared with recipients with
IGF, whereas recipients at other centers were treated similarly
regardless of their DGF status. This variation underscores the
lack of consensus in whether DGF should be regarded as a
contraindication to ESW. Resembling the inconsistent prac-
tice pattern observed in our study, previous clinical trials of
ESW have used mixed approaches on DGF. Some investiga-
tors viewed DGF as a contraindication for ESW. Woodle et al.2
excluded recipients with DGF at enrollment, stating it is a
known risk factor for acute rejection. The FREEDOM trial3
also excluded those with DGF from their per-protocol anal-
yses. In contrast, other trials did not restrict the study partic-
ipants by their DGF status. The ATLAS trial4 and a trial by
Laftavi et al.5 included those with DGF, who constituted about
30% of their study populations. Montagnino et al.6 included
those with DGF, using a more flexible protocol in which
the withdrawal of steroid could be delayed (beyond 7 days
post-KT) or cancelled based on the rate of graft function re-
covery. These variations, found both in practice and research,
demonstrates the knowledge gap in the interaction between
DGF and ESW.
The effect modification observed in our study supports that
DGF could be a reason to consider CSM over ESW for initial

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A Acute rejection, 1-year

IGF DGF
Subgroup N IGF DGF Interaction P

Overall 110018 1.16 (1.09−1.23) 1.12 (1.02−1.23) 0.6

Recipient age 19−64 88248 1.18 (1.10−1.27) 1.15 (1.03−1.27) 0.6

65+ 21770 1.04 (0.90−1.20) 1.04 (0.84−1.30) 1

Year of transplant 2005−2011 52626 1.12 (1.03−1.22) 1.08 (0.95−1.22) 0.6

2012−2017 57392 1.19 (1.08−1.30) 1.17 (1.02−1.35) 0.9

Induction agent ATG 55884 1.30 (1.20−1.42) 1.41 (1.24−1.61) 0.3

IL2RA 18785 1.28 (1.07−1.54) 0.97 (0.74−1.28) 0.1

Alem 14375 0.95 (0.82−1.11) 0.85 (0.68−1.05) 0.4

None 14192 1.01 (0.85−1.20) 0.89 (0.68−1.17) 0.5

Others 6782 0.70 (0.56−0.89) 1.03 (0.76−1.38) 0.04

Panel reactive antibody 0−9 58388 1.12 (1.03−1.22) 1.07 (0.95−1.21) 0.5

10−79 26661 1.00 (0.88−1.13) 1.03 (0.86−1.24) 0.7

80−100 18663 1.43 (1.24−1.64) 1.39 (1.11−1.75) 0.9

Donation after cardiac death No 92470 1.14 (1.07−1.22) 1.14 (1.03−1.27) 1

Yes 17548 1.26 (1.06−1.50) 1.07 (0.88−1.30) 0.2

HLA−A mismatches 0 17033 1.10 (0.92−1.31) 1.39 (1.05−1.84) 0.2

1 40840 1.22 (1.11−1.35) 1.22 (1.05−1.41) 0.9

2 52145 1.13 (1.03−1.23) 1.00 (0.88−1.14) 0.1

HLA−B mismatches 0 12575 1.32 (1.08−1.61) 1.39 (0.97−1.99) 0.8

1 26609 1.13 (0.99−1.28) 1.12 (0.92−1.36) 0.9

2 70834 1.15 (1.06−1.24) 1.12 (1.00−1.25) 0.7

HLA−DR mismatches 0 22938 1.03 (0.89−1.20) 1.56 (1.23−1.98) 0.004

1 49836 1.23 (1.13−1.35) 0.92 (0.80−1.06) <0.001

2 37244 1.14 (1.03−1.27) 1.23 (1.07−1.42) 0.4

0.70 0.80 1.0 1.25 1.5

Adjusted Odds Ratio for Acute Rejection

Figure 3. DGF-ESW interaction was generally homogeneous across subgroups and across KT outcomes. (A) Acute rejection, 1-year.
(B) Death-censored graft failure. (C) Death. Estimates are aORs for acute rejection and aHRs for other outcomes, followed by 95% CIs.
A low (,0.05) interaction P value indicates the association between ESW and the transplant outcome was significantly different be-
tween the IGF and DGF populations. Alem, alemtuzumab; ATG, anti-thymocyte globulin; IL2RA, IL-2 receptor antagonists.

maintenance immunosuppression. ESW has been deemed
viable because previous studies showed only marginal increases
in the risk of graft failure, accompanied by decreases in ad-
verse events.3,4,11–13,31–33 However, we found the increase in
the hazard of graft failure associated with ESW was more
pronounced (16% versus 6%) among recipients with DGF
than among those with IGF, and that the decrease in the
hazard of death associated with ESW was observed only
among recipients with IGF. Although the choice of ESW
versus CSM should be individualized according to the recip-
ient’s overall risk profile rather than a single risk fac-
tor,15,34,35 DGF appears to be an element of the risk profile
that suggests CSM over ESW. In addition, DGF is unique in
that it is a post-KT outcome that can still inform the initial
maintenance immunosuppression strategy. The withdrawal
of steroid can be postponed or cancelled according to the rate
of graft function recovery. A similar protocol was used by
Montagnino et al.6
Although the exact mechanism through which DGF mod-
ifies the association between ESW and KT outcomes remains
unclear, the findings from our cause-specific mortality anal-
yses and stratified analyses provide some implications. First,
the effect modification of DGF on the association between
ESW and patient death seems to have been primarily driven
by death due to cardiovascular disease. ESW was associated
with a decreased hazard of cardiovascular disease–related
death among those with IGF but not among those with
DGF. In contrast, the association of ESW with death due to

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 CLINICAL RESEARCH www.jasn.org

B Death-censored graft failure

IGF DGF
Subgroup N IGF DGF Interaction P

Overall 110018 1.06 (1.01−1.12) 1.16 (1.08−1.26) 0.04

Recipient age 19−64 88248 1.07 (1.01−1.13) 1.16 (1.06−1.26) 0.1

65+ 21770 1.04 (0.91−1.19) 1.19 (1.00−1.42) 0.2

Year of transplant 2005−2011 52626 1.07 (1.01−1.14) 1.20 (1.10−1.32) 0.03

2012−2017 57392 1.02 (0.90−1.14) 1.07 (0.92−1.24) 0.6

Induction agent ATG 55884 1.01 (0.94−1.09) 1.11 (0.99−1.24) 0.2

IL2RA 18785 1.18 (1.01−1.38) 1.29 (1.00−1.67) 0.5

Alem 14375 1.04 (0.92−1.19) 0.96 (0.80−1.14) 0.4

None 14192 1.24 (1.08−1.42) 1.46 (1.20−1.78) 0.2

Others 6782 0.91 (0.74−1.11) 1.26 (0.98−1.61) 0.04

Panel reactive antibody 0−9 58388 1.05 (0.98−1.12) 1.14 (1.03−1.26) 0.1

10−79 26661 1.03 (0.93−1.14) 1.23 (1.06−1.42) 0.04

80−100 18663 1.14 (1.00−1.30) 1.22 (0.99−1.51) 0.6

Donation after cardiac death No 92470 1.08 (1.02−1.14) 1.15 (1.05−1.25) 0.2

Yes 17548 0.90 (0.76−1.07) 1.21 (1.03−1.42) 0.01

HLA−A mismatches 0 17033 1.02 (0.88−1.17) 1.13 (0.89−1.43) 0.4

1 40840 1.09 (1.00−1.19) 1.23 (1.09−1.39) 0.1

2 52145 1.06 (0.98−1.14) 1.13 (1.01−1.26) 0.3

HLA−B mismatches 0 12575 0.95 (0.80−1.12) 1.35 (1.02−1.79) 0.03

1 26609 0.97 (0.87−1.09) 1.16 (0.98−1.37) 0.1

2 70834 1.12 (1.05−1.19) 1.15 (1.05−1.26) 0.6

HLA−DR mismatches 0 22938 0.97 (0.86−1.09) 1.25 (1.02−1.54) 0.03

1 49836 1.08 (1.00−1.17) 1.12 (1.00−1.26) 0.6

2 37244 1.10 (1.01−1.20) 1.19 (1.06−1.34) 0.3

0.70 0.80 1.0 1.25 1.5

Adjusted Hazard Ratio for Graft Failure

Figure 3. Continued.

infection, malignancy, or other causes did not significantly
vary by DGF status. However, this finding should be interpre-
ted with caution given that cause of death was unavailable in
our data set for 50% of the deaths. Second, our various strat-
ified analyses mostly showed a consistent DGF-ESW interac-
tion across the strata. For instance, despite being a possible
risk factor for DGF36 and arguably an indication for ESW,37
older recipient age does not seem to influence the DGF-ESW
interaction observed in our study. On the other hand, the
DGF-ESW interaction appeared slightly heterogeneous
when stratified by induction agent and by the number of
HLA mismatches.
Our study has several limitations. First, the findings from
this observational study do not directly signify causal effects.
Our findings are hypothesis generating but not confirmatory
because they are at risk of selection bias, confounding by
indication, and unmeasured confounders. We attempted
to minimize this limitation by using IPTW and controlling
for an extensive set of potential confounders. Second, we
treated acute rejection as a binary outcome and thus were
not able to capture any differences in timing, severity, or
recurrences of acute rejection. Additionally, we did not
have data on other relevant clinical information, such as
steroid dose or the duration or severity of DGF. Lastly, our
study population was restricted to those who received tacro-
limus and mycophenolate. Our finding might not be gener-
alizable to those who receive other agents for maintenance
immunosuppression.
In conclusion, ESW was associated with a minimal increase
in graft failure and a decrease in mortality among recipients of
KT with IGF, but with a more pronounced increase in graft
failure and no difference in mortality among those with DGF.

182 JASN JASN 31: 175–185, 2020

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C Death
IGF DGF
Subgroup N IGF DGF Interaction P

Overall 110018 0.89 (0.86−0.93) 1.00 (0.94−1.07) 0.003

Recipient age 19−64 88248 0.92 (0.87−0.97) 1.00 (0.93−1.09) 0.1

65+ 21770 0.86 (0.80−0.92) 1.00 (0.90−1.11) 0.02

Year of transplant 2005−2011 52626 0.90 (0.86−0.95) 0.99 (0.93−1.07) 0.02

2012−2017 57392 0.85 (0.77−0.94) 1.00 (0.87−1.14) 0.1

Induction agent ATG 55884 0.89 (0.84−0.94) 0.94 (0.86−1.03) 0.3

IL2RA 18785 0.91 (0.81−1.01) 1.23 (1.03−1.46) 0.004

Alem 14375 0.87 (0.78−0.97) 1.00 (0.85−1.18) 0.1

None 14192 0.95 (0.85−1.06) 0.99 (0.84−1.17) 0.7

Others 6782 0.84 (0.71−1.00) 1.07 (0.85−1.35) 0.1

Panel reactive antibody 0−9 58388 0.90 (0.86−0.95) 0.99 (0.91−1.07) 0.04

10−79 26661 0.89 (0.82−0.96) 1.05 (0.92−1.19) 0.02

80−100 18663 0.93 (0.82−1.05) 1.04 (0.85−1.26) 0.3

Donation after cardiac death No 92470 0.89 (0.86−0.93) 1.03 (0.96−1.10) <0.001

Yes 17548 0.92 (0.80−1.06) 0.91 (0.79−1.05) 0.9

HLA−A mismatches 0 17033 0.86 (0.77−0.95) 0.96 (0.81−1.14) 0.2

1 40840 0.93 (0.87−0.99) 1.02 (0.92−1.13) 0.1

2 52145 0.89 (0.84−0.94) 1.02 (0.93−1.12) 0.01

HLA−B mismatches 0 12575 0.86 (0.77−0.97) 0.95 (0.77−1.16) 0.4

1 26609 0.92 (0.85−1.00) 0.90 (0.79−1.03) 0.8

2 70834 0.90 (0.85−0.94) 1.06 (0.98−1.14) <0.001

HLA−DR mismatches 0 22938 0.83 (0.76−0.91) 0.96 (0.82−1.12) 0.1

1 49836 0.93 (0.87−0.99) 1.01 (0.92−1.11) 0.1

2 37244 0.90 (0.84−0.97) 1.03 (0.93−1.14) 0.03

0.70 0.80 1.0 1.25 1.5

Adjusted Hazard Ratio for Death

Figure 3. Continued.

KT centers appear to have inconsistent practices regarding seen as an official policy of or interpretation by the SRTR or the US
the use of ESW in recipients with DGF. Our findings suggest Government.
that DGF is a reason to consider CSM over ESW for initial
maintenance immunosuppression after KT.
DISCLOSURES

Dr. McAdams-DeMarco reports grants from the National Institutes of

ACKNOWLEDGMENTS
The analyses described here are the responsibility of the authors
alone and do not necessarily reflect the views or policies of the
Department of Health and Human Services, nor does mention of
trade names, commercial products, or organizations imply en-
dorsement by the US Government. The data reported here have been
supplied by the Minneapolis Medical Research Foundation as the
contractor for the SRTR. The interpretation and reporting of these
data are the responsibility of the author(s) and in no way should be
Health (NIH), during the conduct of the study. Dr. Coresh reports grants
from the NIH and grants from the National Kidney Foundation, during the
conduct of the study. Dr. Segev reports honoraria from Sanofi, honoraria from
Novartis, and honoraria from CSL Behring, outside the submitted work.
FUNDING
This work was supported by the American Society of Nephrology and Mogam
Science Scholarship Foundation (Dr. Bae), and the National Institute of Diabetes
and Digestive and Kidney Diseases (K23DK115908 to Dr. Garonzik Wang,

JASN 31: 175–185, 2020 Steroid and Delayed Graft Function 183
 CLINICAL RESEARCH www.jasn.org
F32DK113719 to Dr. Jackson, R01DK120518 to Dr. McAdams-DeMarco,
R01DK102981 to Dr. Brennan, Dr. Lentine, and Dr. Segev, and K24DK101828
to Dr. Segev).
SUPPLEMENTAL MATERIAL
This article contains the following supplemental material
online at http://jasn.asnjournals.org/lookup/suppl/doi:10.1681/
ASN.2019040416/-/DCSupplemental.
Supplemental Figure 1. Kaplan-Meier cumulative incidence plot
for death-censored graft failure and death.
Supplemental Table 1. Coefficients from the inverse probability of
treatment weights model.
REFERENCES
1. Hart A, Smith JM, Skeans MA, Gustafson SK, Wilk AR, Robinson A, et al.:
OPTN/SRTR 2016 annual data report: Kidney. Am J Transplant 18
[Suppl 1]: 18–113, 2018
2. Woodle ES, First MR, Pirsch J, Shihab F, Gaber AO, Van Veldhuisen P;
Astellas Corticosteroid Withdrawal Study Group: A prospective, ran-
domized, double-blind, placebo-controlled multicenter trial compar-
ing early (7 day) corticosteroid cessation versus long-term, low-dose
corticosteroid therapy. Ann Surg 248: 564–577, 2008
3. Vincenti F, Schena FP, Paraskevas S, Hauser IA, Walker RG, Grinyo
J; FREEDOM Study Group: A randomized, multicenter study of
steroid avoidance, early steroid withdrawal or standard steroid
therapy in kidney transplant recipients. Am J Transplant 8: 307–
316, 2008
4. Vítko S, Klinger M, Salmela K, Wlodarczyk Z, Tydèn G, Senatorski G,
et al.: Two corticosteroid-free regimens-tacrolimus monotherapy
after basiliximab administration and tacrolimus/mycophenolate
mofetil-in comparison with a standard triple regimen in renal trans-
plantation: Results of the Atlas study. Transplantation 80: 1734–
1741, 2005
5. Laftavi MR, Stephan R, Stefanick B, Kohli R, Dagher F, Applegate M, et al.:
Randomized prospective trial of early steroid withdrawal compared with
low-dose steroids in renal transplant recipients using serial protocol bi-
opsies to assess efficacy and safety. Surgery 137: 364–371, 2005
6. Montagnino G, Sandrini S, Iorio B, Schena FP, Carmellini M, Rigotti P,
et al.: A randomized exploratory trial of steroid avoidance in renal
transplant patients treated with everolimus and low-dose cyclosporine.
Nephrol Dial Transplant 23: 707–714, 2008
7. Rostaing L, Cantarovich D, Mourad G, Budde K, Rigotti P, Mariat C,
et al.; CARMEN Study Group: Corticosteroid-free immunosuppression
with tacrolimus, mycophenolate mofetil, and daclizumab induction in
renal transplantation. Transplantation 79: 807–814, 2005
8. Cantarovich D, Rostaing L, Kamar N, Saint-Hillier Y, Ducloux D, Mourad G,
et al.; FRANCIA Study Trial Investigators Group: Corticosteroid avoidance
in adult kidney transplant recipients under rabbit anti-T-lymphocyte
globulin, mycophenolate mofetil and delayed cyclosporine micro-
emulsion introduction. Transpl Int 23: 313–324, 2010
9. Matas AJ, Kandaswamy R, Gillingham KJ, McHugh L, Ibrahim H, Kasiske
B, et al.: Prednisone-free maintenance immunosuppression-a 5-year
experience. Am J Transplant 5: 2473–2478, 2005
10. Rizzari MD, Suszynski TM, Gillingham KJ, Dunn TB, Ibrahim HN, Payne
WD, et al.: Ten-year outcome after rapid discontinuation of predni-
sone in adult primary kidney transplantation. Clin J Am Soc Nephrol
7: 494–503, 2012
11. Knight SR, Morris PJ: Steroid avoidance or withdrawal after renal
transplantation increases the risk of acute rejection but decreases
184 JASN
cardiovascular risk. A meta-analysis. Transplantation 89: 1–14,
2010
12. Rike AH, Mogilishetty G, Alloway RR, Succop P, Roy-Chaudhury P,
Cardi M, et al.: Cardiovascular risk, cardiovascular events, and
metabolic syndrome in renal transplantation: Comparison of early
steroid withdrawal and chronic steroids. Clin Transplant 22: 229–
235, 2008
13. Nikkel LE, Mohan S, Zhang A, McMahon DJ, Boutroy S, Dube G, et al.:
Reduced fracture risk with early corticosteroid withdrawal after kidney
transplant. Am J Transplant 12: 649–659, 2012
14. Dharnidharka VR, Schnitzler MA, Chen J, Brennan DC, Axelrod D,
Segev DL, et al.: Differential risks for adverse outcomes 3 years after
kidney transplantation based on initial immunosuppression regimen:
A national study. Transpl Int 29: 1226–1236, 2016
15. Sprangers B, Kuypers DR, Vanrenterghem Y: Immunosuppression:
Does one regimen fit all? Transplantation 92: 251–261, 2011
16. Siedlecki A, Irish W, Brennan DC: Delayed graft function in the kidney
transplant. Am J Transplant 11: 2279–2296, 2011
17. Wu WK, Famure O, Li Y, Kim SJ: Delayed graft function and the risk of
acute rejection in the modern era of kidney transplantation. Kidney Int
88: 851–858, 2015
18. Yarlagadda SG, Coca SG, Formica RN Jr., Poggio ED, Parikh CR: As-
sociation between delayed graft function and allograft and patient
survival: A systematic review and meta-analysis. Nephrol Dial Trans-
plant 24: 1039–1047, 2009
19. Tapiawala SN, Tinckam KJ, Cardella CJ, Schiff J, Cattran DC, Cole EH,
et al.: Delayed graft function and the risk for death with a functioning
graft. J Am Soc Nephrol 21: 153–161, 2010
20. Perico N, Cattaneo D, Sayegh MH, Remuzzi G: Delayed graft function
in kidney transplantation. Lancet 364: 1814–1827, 2004
21. Schröppel B, Legendre C: Delayed kidney graft function: From mech-
anism to translation. Kidney Int 86: 251–258, 2014
22. Irish WD, Ilsley JN, Schnitzler MA, Feng S, Brennan DC: A risk pre-
diction model for delayed graft function in the current era of de-
ceased donor renal transplantation. Am J Transplant 10: 2279–2286,
2010
23. United Network for Organ Sharing: Adult kidney transplant recipient
registration worksheet. Available at: https://unos.org/wp-content/
uploads/unos/Adult_TRR_Kidney.pdf. Accessed September 25, 2019
24. Gilks WR, Clayton DG, Spiegelhalter DJ, Best NG, McNeil AJ, Sharples
LD, et al.: Modelling complexity: Applications of Gibbs sampling in
medicine. J R Stat Soc B 55: 39–52, 1993
25. Hernán MA, Alonso A, Logan R, Grodstein F, Michels KB, Willett WC,
et al.: Observational studies analyzed like randomized experiments: An
application to postmenopausal hormone therapy and coronary heart
disease. Epidemiology 19: 766–779, 2008
26. Lentine KL, Gheorghian A, Axelrod D, Kalsekar A, L’italien G, Schnitzler
MA: The implications of acute rejection for allograft survival in con-
temporary U.S. kidney transplantation. Transplantation 94: 369–376,
2012
27. Massie AB, Kucirka LM, Segev DL: Big data in organ transplantation:
Registries and administrative claims [published correction appears in
Am J Transplant 14: 2673, 2014]. Am J Transplant 14: 1723–1730,
2014
28. Lau B, Cole SR, Gange SJ: Competing risk regression models for epi-
demiologic data. Am J Epidemiol 170: 244–256, 2009
29. Ravindra KV, Sanoff S, Vikraman D, Zaaroura A, Nanavati A, Sudan D,
et al.: Lymphocyte depletion and risk of acute rejection in renal trans-
plant recipients at increased risk for delayed graft function. Am J
Transplant 19: 781–789, 2019
30. Louis TA, Zeger SL: Effective communication of standard errors and
confidence intervals. Biostatistics 10: 1–2, 2009
31. Pascual J, Royuela A, Galeano C, Crespo M, Zamora J: Very early
steroid withdrawal or complete avoidance for kidney transplant re-
cipients: A systematic review. Nephrol Dial Transplant 27: 825–832,
2012
JASN 31: 175–185, 2020

32. Haller MC, Royuela A, Nagler EV, Pascual J, Webster AC: Steroid
avoidance or withdrawal for kidney transplant recipients. Cochrane
Database Syst Rev CD005632, 2016
33. Cantarovich D, Rostaing L, Kamar N, Ducloux D, Saint-Hillier Y, Mourad
G, et al.; FRANCIA Study Trial Investigators Group: Early corticosteroid
avoidance in kidney transplant recipients receiving ATG-F induction:
5-year actual results of a prospective and randomized study. Am J
Transplant 14: 2556–2564, 2014
34. Kidney disease: Improving Global Outcomes (KDIGO) transplant work
Group: KDIGO clinical practice guideline for the care of kidney trans-
plant recipients. Am J Transplant 9: S1–S155, 2009
35. Wavamunno MD, Chapman JR: Individualization of immunosuppression:
Concepts and rationale. Curr Opin Organ Transplant 13: 604–608, 2008
JASN 31: 175–185, 2020
www.jasn.org CLINICAL RESEARCH
36. Giral M, Bertola JP, Foucher Y, Villers D, Bironneau E, Blanloeil Y, et al.:
Effect of brain-dead donor resuscitation on delayed graft function:
Results of a monocentric analysis. Transplantation 83: 1174–1181,
2007
37. Krenzien F, ElKhal A, Quante M, Rodriguez Cetina Biefer H, Hirofumi U,
Gabardi S, et al.: A rationale for age-adapted immunosuppres-
sion in organ transplantation. Transplantation 99: 2258–2268,
2015
See related editorial, “When Less Becomes More: Life and Losses without the
‘Roids’?” on pages 6–8.
Steroid and Delayed Graft Function 185
Supplemental material to:
Bae S, et al. Early Steroid Withdrawal in Deceased-Donor Kidney Transplant Recipients with Delayed
Graft Function.

Table of Contents
Supplemental Figure 1. Kaplan-Meier cumulative incidence plot for death-censored graft failure and
death. .................................................................................................................................................... 1
Supplemental Table 1. Coefficients from the inverse probability of treatment weights model. .............. 2
Supplemental Figure 1. Kaplan-Meier cumulative incidence plot for death-censored graft
failure and death.

(a) Death-censored graft failure

(b) Death

ESW, early steroid withdrawal; CSM, conventional steroid maintenance; DGF, delayed graft function;
and IGF, immediate graft function.

1
Supplemental Table 1. Coefficients from the inverse probability of treatment weights model.

Factor Log(OR) 95% CI

Constant -0.892 (-1.300, -0.483)
Recipient factors
Age (<40) -0.003 (-0.007, 0.001)
Age (≥40) 0.003 (0.001, 0.004)
Race (Ref: White)
Black -0.187 (-0.223, -0.151)
Hispanic -0.080 (-0.123, -0.037)
Other -0.027 (-0.078, 0.024)
Female -0.046 (-0.073, -0.019)
Panel reactive antibody (Ref: 0-9)
10-79 -0.230 (-0.264, -0.196)
80-100 -0.667 (-0.729, -0.604)
Missing -0.157 (-0.222, -0.091)
Previous transplant -0.547 (-0.611, -0.483)
BMI, kg/m2 (Ref: 18.5-25)
<18.5 -0.006 (-0.121, 0.109)
25-30 -0.010 (-0.042, 0.022)
≥30 0.010 (-0.023, 0.043)
Missing 0.076 (-0.058, 0.209)
Diabetes (Ref: No)
Yes -0.004 (-0.053, 0.046)
Missing -0.090 (-0.259, 0.078)
Hypertension (Ref: No)
Yes -0.003 (-0.049, 0.043)
Missing -0.138 (-0.195, -0.081)
Cause of ESRD (Ref: Diabetes)
Glomerulonephritis -0.150 (-0.209, -0.091)
Hypertension 0.010 (-0.045, 0.066)
Others -0.054 (-0.111, 0.002)
Preemptive transplant 0.010 (-0.054, 0.074)
Years on dialysis (<2) 0.030 (-0.001, 0.061)
Years on dialysis (≥2) 0.000 (-0.006, 0.005)
Years on dialysis, missing -0.014 (-0.164, 0.136)
Serum albumin, g/dl (<3) -0.053 (-0.167, 0.061)
Serum albumin, g/dl (≥3) 0.030 (0.001, 0.060)
Serum albumin, missing -0.077 (-0.153, -0.002)
Periphreral artery disease (Ref: No)
Yes 0.062 (0.009, 0.116)
Unknown/missing 0.156 (0.058, 0.254)
Malignancy (Ref: No)
Yes -0.033 (-0.089, 0.022)
Unknown/missing 0.078 (-0.037, 0.192)

2
HCV(+) 0.067 (-0.002, 0.136)
HBV(+) -0.016 (-0.065, 0.033)
HBV, missing 0.102 (0.056, 0.148)
Education level (Ref: Below high school)
Above high school -0.002 (-0.029, 0.025)
Missing 0.082 (0.027, 0.136)
Medicare as primary payer -0.050 (-0.078, -0.021)
Donor factors
Age (<25) 0.002 (-0.002, 0.006)
Age (≥25) -0.001 (-0.002, 0.000)
Female 0.007 (-0.020, 0.034)
Race (Ref: White)
Black 0.017 (-0.021, 0.055)
Hispanic -0.049 (-0.089, -0.009)
Other -0.035 (-0.109, 0.038)
BMI, kg/m2 (Ref: 18.5-25)
<18.5 -0.005 (-0.070, 0.061)
25-30 -0.011 (-0.042, 0.020)
≥30 -0.026 (-0.059, 0.008)
Missing -0.142 (-0.241, -0.043)
HLA-A mismatches (Ref: 0)
1 0.001 (-0.049, 0.050)
2 -0.011 (-0.060, 0.039)
HLA-B mismatches (Ref: 0)
1 -0.088 (-0.148, -0.028)
2 -0.087 (-0.145, -0.028)
HLA-DR mismatches (Ref: 0)
1 -0.028 (-0.067, 0.011)
2 -0.060 (-0.102, -0.019)
Induction agent (Ref: ATG)
None 0.006 (-0.039, 0.052)
IL2RA -0.551 (-0.609, -0.493)
Alem 0.973 (0.915, 1.031)
Others 0.217 (0.119, 0.315)
HCV(+) 0.117 (0.024, 0.211)
Donation after cardiac death -0.088 (-0.130, -0.045)
Diabetes (Ref: No)
Yes 0.035 (-0.016, 0.086)
Missing -0.056 (-0.272, 0.161)
Hypertension (Ref: No)
Yes 0.002 (-0.031, 0.036)
Missing 0.007 (-0.185, 0.199)
Stroke as the cause of donor death -0.016 (-0.047, 0.016)
Machine perfusion (Ref: No)
Yes -0.037 (-0.070, -0.004)
Missing -0.034 (-0.115, 0.048)
3
Terminal serum creatinine, mg/dl (<0.8) 0.016 (-0.096, 0.129)
Terminal serum creatinine, mg/dl (≥0.8) -0.012 (-0.029, 0.006)
Terminal serum creatinine, missing 1.118 (0.434, 1.801)
Cold ischemic time, Hr -0.002 (-0.004, -0.001)
Cold ischemic time, missing 0.307 (0.155, 0.460)
Delayed graft function -0.474 (-1.282, 0.335)
Among those with delayed graft function, add the terms below
Age (<40) 0.010 (0.000, 0.019)
Age (≥40) -0.002 (-0.005, 0.001)
Race (Ref: White)
Black 0.005 (-0.064, 0.073)
Hispanic 0.033 (-0.050, 0.116)
Other 0.083 (-0.019, 0.185)
Female -0.042 (-0.102, 0.018)
Panel reactive antibody (Ref: 0-9)
10-79 0.071 (0.006, 0.136)
80-100 0.114 (0.013, 0.215)
Missing 0.055 (-0.077, 0.187)
Previous transplant 0.114 (0.005, 0.223)
2
BMI, kg/m (Ref: 18.5-25)
<18.5 0.009 (-0.285, 0.303)
25-30 0.030 (-0.041, 0.101)
≥30 0.016 (-0.055, 0.087)
Missing -0.042 (-0.322, 0.239)
Diabetes (Ref: No)
Yes 0.013 (-0.087, 0.112)
Missing 0.111 (-0.238, 0.461)
Hypertension (Ref: No)
Yes 0.025 (-0.072, 0.121)
Missing 0.060 (-0.055, 0.175)
Cause of ESRD (Ref: Diabetes)
Glomerulonephritis -0.015 (-0.135, 0.105)
Hypertension -0.028 (-0.136, 0.080)
Others -0.029 (-0.142, 0.083)
Preemptive transplant -0.060 (-0.254, 0.134)
Years on dialysis (<2) -0.046 (-0.121, 0.029)
Years on dialysis (≥2) -0.003 (-0.013, 0.007)
Years on dialysis, missing -0.311 (-0.683, 0.061)
Serum albumin, g/dl (<3) -0.037 (-0.267, 0.193)
Serum albumin, g/dl (≥3) 0.052 (-0.008, 0.111)
Serum albumin, missing -0.006 (-0.153, 0.142)
Peripheral artery disease (Ref: No)
Yes -0.064 (-0.166, 0.039)
Unknown/missing -0.230 (-0.449, -0.012)
Malignancy (Ref: No)
Yes 0.068 (-0.046, 0.182)
4
 Unknown/missing 0.305 (0.058, 0.551)
HCV(+) -0.107 (-0.245, 0.031)
HBV(+) -0.043 (-0.138, 0.052)
HBV, missing -0.154 (-0.241, -0.066)
Education level (Ref: Below high school)
Above high school -0.018 (-0.074, 0.038)
Missing -0.155 (-0.268, -0.043)
Medicare as primary payer 0.038 (-0.016, 0.093)
Age (<25) 0.000 (-0.009, 0.009)
Age (≥25) 0.000 (-0.003, 0.003)
Female 0.010 (-0.046, 0.067)
Race (Ref: White)
Black 0.011 (-0.069, 0.090)
Hispanic 0.058 (-0.024, 0.139)
Other 0.030 (-0.118, 0.178)
BMI, kg/m2 (Ref: 18.5-25)
<18.5 -0.029 (-0.190, 0.132)
25-30 0.013 (-0.055, 0.081)
≥30 0.038 (-0.032, 0.107)
Missing 0.203 (0.006, 0.401)
HLA-A mismatches (Ref: 0)
1 -0.021 (-0.126, 0.084)
2 0.013 (-0.092, 0.117)
HLA-B mismatches (Ref: 0)
1 0.050 (-0.083, 0.183)
2 0.063 (-0.066, 0.192)
HLA-DR mismatches (Ref: 0)
1 0.013 (-0.072, 0.098)
2 0.026 (-0.063, 0.115)
Induction agent (Ref: ATG)
None 0.173 (0.085, 0.260)
IL2RA -0.145 (-0.241, -0.049)
Alem 0.018 (-0.053, 0.088)
Others 0.140 (-0.025, 0.304)
HCV(+) -0.003 (-0.199, 0.192)
Donation after cardiac death -0.035 (-0.112, 0.041)
Diabetes (Ref: No)
Yes -0.031 (-0.132, 0.069)
Missing -0.048 (-0.476, 0.379)
Hypertension (Ref: No)
Yes -0.049 (-0.115, 0.017)
Missing 0.112 (-0.268, 0.491)
Stroke as the cause of donor death 0.023 (-0.041, 0.087)
Machine perfusion (Ref: No)
Yes 0.034 (-0.029, 0.097)
Missing -0.129 (-0.321, 0.063)
5
Terminal serum creatinine, mg/dl (<0.8) -0.170 (-0.416, 0.075)
Terminal serum creatinine, mg/dl (≥0.8) 0.033 (0.007, 0.059)
Terminal serum creatinine, missing -0.608 (-2.004, 0.788)
Cold ischemic time, Hr 0.001 (-0.002, 0.004)
Cold ischemic time, missing -0.242 (-0.561, 0.076)