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Timing and Predictors of Early Urologic and Infectious

Complications After Renal Transplant: An Analysis of a
New York Statewide Database
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Abstract Key words: .1:9@=62:98>87A >1@=.7A =62:9<>;2>?8>87

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Objectives: The most common complications after :=*<4)
renal transplant are urologic and are a cause of
significant morbidity in a vulnerable population. We Introduction

As of January 2014, there were more than 660 000

sought to characterize the timing and predictors of

patients living with end-stage renal disease (ESRD)

urologic complications after renal transplant using a
statewide database.
Materials and Methods: We queried the New York in the United States; of these, 29.2% had a functioning
Statewide Planning and Research Cooperative System renal transplant.1 Renal transplant is the criterion
database to identify patients who underwent renal standard treatment for patients with ESRD, with a
total of 17 500 renal transplant procedures taking
transplant from 2005 to 2013. Postoperative com-
place in the United States in 2012 alone.2
plications included hydronephrosis, ureteral stricture,
Urologic complications occur in 2.5% to 14% of
vesicoureteral reflux, nephrolithiasis, and urinary tract

renal transplants and are the most common technical

infections. Cox proportional hazards model was used

adverse events after renal transplant.3-7 These

to assess independent predictors of urologic com-

complications may result in significant morbidity

plications.

and graft loss, especially given the patients’ immuno-

Results: In total, 9038 patients were included in the
analyses. Urologic complications occurred in 11.3% of
patients and included hydronephrosis (12.0%), suppression and chronic comorbidities.8-10 A number
nephrolithiasis (2.8%), ureteral stricture (2.4%), and of posttransplant urologic complications have been
vesicoureteral reflux (1.5%). We found that 23% identified and may be categorized as immediate or
delayed complications. Immediate urologic com-
experienced at least one urinary tract infection. On
plications include hematuria, urinary extravasation,
multivariate analysis, predictors of urologic com-
and urinary obstruction. Potential long-term com-
plications included medicare insurance, hypertension,

plications include nephrolithiasis, vesicoureteral

and prior urinary tract infection. Graft recipients from

reflux (VUR), and ureteral stricture disease.11

living donors were less likely to experience urologic

The timing at which patients are at risk for

complications than deceased-donor kidney recipients

urologic complications is not well characterized, thus

(P < .001).
Conclusions: Urologic complications occur in a
significant proportion of renal transplants. Further
study is needed to identify risk factors for com-
plications after renal transplantation to decrease
morbidity in this vulnerable population.
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potentially limiting targeted follow-up care.12,13
Although the role of the urologist in the renal
transplant population has diminished over time, the
preoperative urologic assessment is crucial to
identify potential issues that may lead to graft
dysfunction or complications. During the post-

transplant period, technical complications may

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require specialized care by urologists as well.

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A number of studies have investigated urologic

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complications after renal transplant as well as
+(*+,)'&-',"-&*,* '&-(',$&',)')*%,--!#-!!! risk factors for the aforementioned complications.

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However, these are generally limited to single
institution studies with few transplant surgeons
included in the analyses. In this study, we sought to
utilize a statewide administrative database to
investigate the rate and timing of urologic
complications after renal transplant surgery in the
state of New York.
Materials and Methods
+*$,#*'
We utilized the New York Statewide Planning and
Research Cooperative System administrative
database, which collected data from 1994 to 2014 on
all inpatient stays and outpatient visits (ambulatory
surgery, emergency department, and outpatient
services) in the state of New York. We identified all
patients who underwent renal transplant surgery
between 2005 and 2014 using International
Classification of Disease, 9th edition (ICD-9) CM
procedure codes 00.91, 00.92, and 00.93. To define a
standard follow-up period for each patient, we
tracked patients for up to 2 years after their initial
presentation. Patients > 18 years old with at least 1
year of follow-up were included in the analysis.
* ,'
The primary outcome analyzed was urologic
complication rate after renal transplant. Urologic
complications were identified by ICD-9 codes and
included ureteral strictures, hydronephrosis, VUR,
and nephrolithiasis (Table 1). Urinary tract infections
(UTIs) within 2 years of transplant were similarly
abstracted. We relied on complications in the
inpatient, ambulatory, and emergency departments
for our analyses. Patients who did not develop a
complication within 2 years of transplant were
censored at the 24-month mark, and those with less
than 24 months of follow-up were censored at the last
&+%(,-) International Classification of Disease, 9th Edition, CM Codes Used to
Identify Comorbid Conditions and Urologic Complications
Disease Code
Urologic complication
Ureteral stricture 593.3
Hydronephrosis 592.0, 592.1, 592.9
Vesicoureteral reflux 593.70, 593.71, 593.72, 593.73
Nephrolithiasis 592.0, 592.1, 592.9
Comorbid condition
Urinary tract infection 599.0, 590.10, 590.11, 590.80, 590.81, 590.9
Hypertension 401.1 to 405.99
Diabetes 250.00 to 250.93
Polycystic kidney disease 753.11, 753.12, 753.13
Glomerulonephritis 580.0 to 583.9
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follow-up visit. Because only the month and year of
admission were available, the date of admission
was normalized to the 15th of the month for each
patient.
#,,#,#*-+$+%(,'
Patient comorbidity was defined using the Elixhauser
Comorbidity Index and specific conditions associated
with the development of ESRD were identified using
ICD-9 codes. These included history of UTIs, history
of nephrolithiasis, history of hypertension, history of
diabetes, history of polycystic kidney disease, and
history of glomerulonephritis. Patient characteristics
such as age, sex, race, ethnicity, and geographic
region were also included in the analysis.
*+*$'*$+(-+#+(','
Follow-up time was calculated from date of renal
transplant, and patients were censored at a
maximum of 2 years. A Cox proportional hazards
model was used to identify predictors of urologic
complications by 2 years after renal transplant.
Variables included donor of the transplanted kidney
(deceased donor, living related donor, or living
unrelated donor), history of UTI, glomerulonephritis,
polycystic kidney disease, hypertension, and
diabetes mellitus in addition to demographic
characteristics, including age, race, and insurance
status. Hazard ratios (HR) and 95% confidence
intervals (CI) were reported. < .05 was considered
significant. All statistical analyses were performed
using SPSS software (SPSS: An IBM Company,
version 23.0, IBM Corporation, Armonk, NY, USA).
Results
A total of 9038 patients were included in the final
analysis. Patient characteristics are listed in Table 2.
Mean age at the time of transplant was 51.5 ± 13.8
years, and our data showed that 61% of patients were
male. Most of the cohort were white (54%), with 22%
having African American (AA) ethnicity. Medicaid
was the primary insurance in 58% of patients, and
most transplants were performed in the New York
City area (67%). Most of the sample had an
Elixhauser Comorbidity Index of 1 or higher (74%),
with 21% having a score over 10. Deceased donor
renal transplant was performed in most of the
patients (57%). A total of 32% of patients had a
history of hypertension and 31% had a history of
 '><89@A(4>A=;A?<#)6=:>,=@;?<A?@1A/<>@>3?<A+:?@86<?@;?;>9@A&0- A5A55!50 667

diabetes. Polycystic kidney disease was found in 4%
and history of glomerulonephritis in 17%.
&+%(,- ) Demographic Characteristics of Patients Receiving Kidney
Transplant
were significant predictors of urologic complications.
Living related renal transplant (HR 0.74; 95% CI,
0.66-0.83) and living unrelated renal transplant (HR
0.72; 95% CI 0.63-0.82) were associated with a
significantly lower risk of urologic complications

(Table 4). Significant predictors of the development

Variable No. of Total Patients

of UTI after renal transplant included increasing age

(%) (N = 9038)

(HR 1.01; 95% CI, 1.09-1.01), female sex (HR 1.74; 95%
Age at transplant (mean ± standard deviation), y 51.49 ± 13.75
Sex

CI, 1.59-1.90), commercial pretransplant history of

Male 5542 (61.3)
Female 3496 (38.7)

UTI (HR 3.37; 95% CI, 3.03-3.75), history of

Race

hypertension (HR 1.14; 95% CI, 1.04-1.26), and history

White 4813 (53.7)
African American 1975 (22.0)

of type 2 diabetes mellitus (HR 1.22; 95% CI, 1.11-1.35).

Other 2177 (24.3)

Similar to the urologic complications, living donor

Ethnicity
Hispanic 1112 (12.5)

grafts were protective against UTIs (Table 4).

Non-Hispanic 7763 (87.5)
Insurance status
Commercial 3240 (35.8)
Medicaid 5262 (58.2)
&+%(,-) Urologic Complications After Renal Transplant
Medicare 406 (4.5)
Other 130 (1.4)
Region Variable Total No. of 1-Year Percent
1 + 2 (east) 1186 (13.1) Patients (%) Complication Occurring
3 + 4 (mid/north) 673 (7.4) (N = 9038) Rate, No. of Within
5 (close to New York City) 471 (5.2) Patients (%) Year 1
6 + 7 + 8 + 9 + 10 (New York City) 6059 (67.0) Hydronephrosis 843 (9.3) 740 (8.2) 67.7
11 (Long Island) 629 (7.2) Ureteral stricture 174 (1.9) 152 (1.7) 68.0
Elixhauser Comorbidity Index Nephrolithiasis 142 (1.6) 106 (1.2) 42.6
0 2381 (26.3) Vesicoureteral reflux 99 (1.1) 85 (0.9) 63.4
1 to 5 3019 (33.4) Urinary tract infection 2100 (23.2) 1857 (20.5) 88.4
6 to 10 1732 (19.2)
> 10 1906 (21.1)
$ ,-)-Kaplan-Meier Survival Plots Depicting Time to Complications After
Type of transplant
Renal Transplant
Living related donor 2397 (26.5)
Living unrelated donor 1527 (16.9)
Deceased donor 5114 (56.6)
Risk factor
Hypertension 2919 (32.3)
Diabetes mellitus 2795 (30.9)
History of urinary tract infection 787 (8.7)
History of nephrolithiasis 103 (1.1)
Polycystic kidney disease 381 (4.2)
Glomerulonephritis 1553 (17.2)

Overall, 11.3% of patients developed a urologic

complication (Table 3) with a median follow-up of
2 years. Hydronephrosis was found in 9.3% (843
patients), with 67.7% of those episodes diagnosed
within the first year after transplant. Ureteral
stricture, nephrolithiasis, and vesicoureteral reflux
were detected in 1.9% (174 patients), 1.6% (142
patients), and 1.1% (99 patients), respectively. Almost
a quarter of patients (23.2%) experienced a UTI, with
88% occurring within the first year after transplant.
Figure 1, A-E, shows Kaplan Meier curves of the
various urologic complications after transplant. Most
urologic complications occurred within the first year
after transplant.
On multivariate analysis, Medicare insurance
versus commercial insurance (HR 1.25; 95% CI, 1.01- !-Nephrolithiasis. !-Vesicoureteral reflux (VUR). !-Hydronephrosis. !
1.53), history of UTI (HR 1.57; 95% CI, 1.37-1.80), and Ureteral stricture. ! Urinary tract infection (UTI). Survival probability has
been scaled according to the relative rarity of these complications. Given the
history of hypertension (HR 1.16; 95% CI, 1.05-1.27) rare occurrence of these complications, the vertical axis was scaled accordingly.
668 '><89@A(4>A=;A?<#)6=:>,=@;?<A?@1A/<>@>3?<A+:?@86<?@;?;>9@A&0- A5A55!50 #)6A/<>@A+:?@86<?@;

&+%(,- ) Multivariate Predictors of Urologic and Infectious Complications After Renal Transplant
Variable Any Urologic Complication Urinary Tract Infection
HR (95% CI) P Value HR (95% CI) P Value
Age (continuous) 1.00 (0.99-1.00) .185 1.01 (1.00-1.01) < .001
Sex
Male 1.0 REF 1.0 REF
Female 0.99 (0.90-1.08) .762 1.74 (1.59-1.90) < .001
Race
White 1.0 REF 1.0 REF
Black 0.94 (0.84-1.05) .260 1.08 (0.96-1.20) .192
Other 0.96 (0.87-1.07) .501 1.04 (0.93-1.15) .528
Insurance
Commercial 1.0 REF 1.0 REF
Medicaid 1.01 (0.91-1.12) .852 1.25 (1.12-1.39) < .001
Medicare 1.25 (1.01-1.53) .036 1.33 (1.08-1.63) .006
Other 1.23 (0.88-1.72) .230 1.06 (0.73-1.54) .749
Type of transplant
Deceased 1.0 REF 1.0 REF
Living related 0.74 (0.66-0.83) < .001 0.62 (0.55-0.69) < .001
Living not related 0.72 (0.63-0.82) < .001 0.64 (0.56-0.74) < .001
Medical history
History of UTI (vs no) 1.57 (1.37-1.80) < .001 5.19 (4.67-5.78) < .001
History of glomerulonephritis (vs no) 0.99 (0.87-1.11) .806 0.92 (0.82-1.04) .189
History of PKD (vs no) 0.95 (0.76-1.17) .610 0.90 (0.73-1.10) .293
History of hypertension (vs no) 1.16 (1.05-1.27) .003 1.18 (1.08-1.30) < .001
History of DM (vs no) 0.92 (0.83-1.02) .119 1.17 (1.07-1.29) .001
 (+*')*%,$#-CI, confidence interval; DM, diabetes mellitus; HR, hazard ratio; PKD, polycystic kidney disease; REF, reference;
UTI, urinary tract infection

Discussion colleagues retrospectively reviewed a cohort of 1698

Urologic and infectious complications after trans-
plant are essential to identify and treat given the risk
of graft failure and immunosuppressed state of
transplant patients. To our knowledge, we are the
first group to identify and characterize urologic and
infectious complications after renal transplant using
a population-level dataset. This has several advan-
tages over single-institution studies as it pools data
from all transplant centers in New York State,
allowing the analysis of a large sample of renal
transplant recipients and the creation of a standard
methodology to capture urologic complications.
Several single institution studies have inves-
tigated predictors of urologic complications using
different outcome measures. An analysis of 634
patients found that 4.6% of patients experienced a
urine leak or urinary obstruction after transplant,
requiring intervention.14 The median follow-up was
1012 days, and the median time to complication was
40 days. On multivariate analysis, only renal artery
multiplicity was found to be significantly associated
with developing complications. Similarly, in another
cohort of 2500 renal transplants, a 5.5% complication
rate was observed, including VUR in 3%, stricture
disease in 1.3%, urine leak in 0.9%, and ureteropelvic
junction obstruction in 0.3%.15 Of the 9038 patients in
our study, we found slightly lower rates of VUR
(1.5%) and higher stricture rates (2.4%). Englesbe and
renal transplants and identified an overall incidence
of urologic complications, defined as urine leak and
ureteral stricture, of 6.2%.10 On multivariate analysis,
they identified male sex, AA ethnicity, and “U” stitch
technique (vs Lich-Gregoir) as independent predic-
tors of complications. Our analyses also identified
male sex and AA as significant predictors of any
urologic complication.
Hydronephrosis of the graft is reported to occur
in 3% to 6.5% of cases with a variety of causes,
including extraluminal (hematoma or lymphocele)
or intraluminal (reflux, obstruction, or blood clot)
causes.3,7 Timing of this complication is dependent
on the associated cause. We were not able to identify
these secondary causes of hydronephrosis given the
limitations of the ICD-9 coding system. However,
within our cohort, most hydronephrosis complications
occurred within 1 year of transplant and the overall
rate was 12%, a rate higher than previously reported.
The incidence of urolithiasis in patients after renal
transplant is reported to be 0.23% to 3%.16-19 In a
single institution retrospective study of 2085 renal
transplants, 21 (1.0%) were found to be diagnosed
with urolithiasis at a mean follow-up of 3.7 years
(0.17-18 y).17 Most of these patients were successfully
treated with extracorporeal shock wave lithotripsy,
and all patients were found to be stone free on
follow-up. This incidence estimate is comparable to
our own of 1.6%. Predisposing risk factors for
 '><89@A(4>A=;A?<#)6=:>,=@;?<A?@1A/<>@>3?<A+:?@86<?@;?;>9@A&0- A5A55!50
urolithiasis in patients after renal transplant include
metabolic abnormalities such as hypocitraturia,
hyperparathyroidism, hypophosphatemia, and
hypercalcemia in addition to gout, female sex, and
recurrent UTI.16,17
Ureteral strictures are reported to occur in 0.6% to
12.5% of renal transplant procedures.20-23 Previously
identified risk factors include male sex, deceased
donor grafts, and the Politano-Leadbetter technique.21
In a study of 1298 renal transplant patients, 3.1%
developed ureteral stenosis, with 75% diagnosed
within the first year of surgery and 65% within the
first 3 months of surgery.24 A similar analysis of 1000
renal transplant patients found an overall incidence
of 3.6% ureteral strictures with a median time to
presentation of 16 weeks after transplant.5 There
have been several proposed mechanisms driving the
development of this complication, including
ischemia, technical issues, rejection, infection, and
external compression.5,23,24 Although our stricture
rate of 2.4% is slightly lower than quoted above,
many patients will still require surgical intervention
for this complication. Treatments include endoscopic
approaches (balloon dilation, chronic stenting,
laser/cold knife incision), which have a success rate
of 60%, and open surgical procedures (ureteral
reimplantation or ureteropelvic anastomosis), which
have success rates of 80% to 100%.20
The reported incidence of VUR ranges from 3.0%
to 12.4%, although notably several of these studies
involved the pediatric population.25-28 In a single
institution study of 2500 transplants over a 16-year
period by a single transplant urologist, symptomatic
VUR was reported in 3% (78 patients).21 The average
time to presentation was 3.5 years (0.5-15 y), and the
most common presentation was recurrent UTI. Most
of these patients were female (80%). A minority
(11.5%) was initially treated with antibiotic therapy
alone, with the remaining patients undergoing
deflux injection or reconstructive surgery. We
reported a VUR of 1.1% of total patients (n = 99),
almost 2% lower than previously reported. Despite
the lower percentage of patients with VUR in our
study, the associated risk of pyelonephritis with VUR
makes it important to monitor these immunosup-
pressed patients.26
The incidence of UTI has significant variability,
ranging from 23% to 75%,29-31 with 2.9% to 27%
experiencing recurrent UTI.29,32 Identification of
patients at risk for UTI may help improve outcomes
669
as it is associated with increased posttransplant
morbidity and worse graft and patient survival.32-34
In our study, the rate of UTI was 23%, similar to
previously reported rates. We identified risk factors
for UTI development including increasing age,
female sex, nonwhite race, pretransplant history of
UTI, hypertension, and type 2 diabetes mellitus,
which are factors similar to those previously
reported.32,35,36 Living donor transplant is associated
with a decreased risk of infectious complications,
which has also been reported.37 Although the reason
for increased UTI risk and complication rate remains
to be determined for deceased donor transplants, this
may be due to colonization in the deceased donor
graft, whereas living donors are extensively evalu-
ated before donation.
It is important to point out the limitations of this
study. The retrospective nature of the analysis
precludes from identifying causal relations between
the risk factor and the urologic complication at
question. Donor characteristics and operative
variables (technique of ureteral anastomosis, stitch
technique, placement of ureteral stents, and so forth)
could not be abstracted and may be associated with
the development of complications.10,14 Our study did
not capture complications that may have been
treated in the outpatient setting. Instead, we relied
on treatment of complications in the inpatient,
ambulatory, and emergency department settings.
This may affect the rate of capture of complications
that may be managed in an outpatient setting. In
addition, the database did not capture medication
information such as steroid use, which may have also
affected postoperative complications. This study also
relied on accurate documentation of postoperative
complications, which have been shown to be reliable
but may underestimate the comorbid condition.38,39
Finally, there is missing preoperative baseline
urologic information such as work-up completed for
voiding dysfunction or if patients required inter-
mittent catheterization. These uncaptured factors
may affect risk of infection. Despite its limitations,
this study identifies several important factors asso-
ciated with increased posttransplant complication
risks.
Conclusions
We identified specific demographic and socio-
economic factors associated with urologic com-
670 '><89@A(4>A=;A?<#)6=:>,=@;?<A?@1A/<>@>3?<A+:?@86<?@;?;>9@A&0- A5A55!50
plications in patients undergoing renal transplant,
including insurance type and history of hypertension
or UTI. This information can be used to help improve
care in this specific patient population and
potentially limit the morbidity associated with such
complications. Future studies identifying solutions
to decrease complications in this vulnerable
population are needed.
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