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38]

Saudi J Kidney Dis Transpl 2021;32(2):307-317

© 2021 Saudi Center for Organ Transplantation SaudiJournal
Saudi
Saudi Journal
Journal
ofKidney
of KidneyDiseases
Diseases
and
and ofTransplantation
Kidney Diseases
Transplantation
and Transplantation

Review Article

Urinary Tract Infection in Renal Transplant Recipient: A Clinical

Comprehensive Review
Priti Meena, Vinant Bhargava, Devinder Singh Rana, Anil Kumar Bhalla

Department of Nephrology, Institute of Renal Science, Sir Gangaram Hospital, New Delhi, India

ABSTRACT. Since the initial times of renal transplantation in the 1950s, understanding various
aspects influencing graft survival and outcome have been progressively improving. However,
infections especially urinary tract infections (UTIs), are an important factor leading to an increase in
morbidity and graft failure. UTI degrades the health-related quality of life and can potentially
impair graft function. UTI occurs in 25% of kidney transplant recipients within one year of
transplant and accounts for 45% of infectious complications. Asymptomatic bacteriuria (ASB),
uncomplicated UTI, and complicated UTI comprise 44%, 32%, and 24% of cases, respectively.
This article reviews important aspects regarding posttransplant UTI, including definition, incidence,
predisposing factors, recommendations, ASB, and controversies in management. UTI after renal
transplantation is still an under-estimated aspect, despite its degrading effects on allograft and
recipient health.

Introduction diagnostic criteria used in the studies. The risk

Following kidney transplantation, urinary tract
infection (UTI) is the most common infection
and the incidence varies from 35% to 60%. It
accounts for approximately 44%–47% of all
infectious complications.1 This considerable
variation in the incidence of UTI could be due
to variability in the local epidemiology, local
outbreaks and difference in the definitions and
Correspondence to:
Dr. Priti Meena,
Department of Nephrology,
Institute of Renal Science,
Sir Gangaram Hospital, New Delhi, India.
E-mail: pritimn@gmail.com
of UTI is highest in the 1st-month post-
transplantation and continues up to three months;
following which this risk reduces.2 UTI in the
post transplant patient is attributed to factors
associated with the host and the causative
organisms. Various predisposing factors for
UTI are shown in Figure 1 and are divided into
preoperative, intraoperative, and postoperative
factors.
Acute, uncomplicated UTIs in adults include
episodes of acute cystitis and acute pyelo-
nephritis in otherwise healthy individuals.
These UTIs are seen mostly in women without
structural and functional abnormalities within
the urinary tract, kidney diseases, or comor-
bidity. These could result in more severe
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308
Figure 1. Predisposing factors for urinary tract infection after renal transplantation.
UTI: Urinary tract infection, AR: Acute rejection, SLE: Systemic lupus erythematosus, CMV:
Cytomegalovirus.
outcomes and therefore need attention.3
A complicated UTI is an infection associated
with a structural or functional abnormality of
the genitourinary tract or in the presence of an
underlying disease, which increases the risks of
an infection or resistance to therapy.4
Host Factors
Some of the risk factors predisposing to UTI
in postrenal transplant patients are common to
the general population. As compared to males,
females are at higher risk due to a shorter
urethra and proximity to the anus. Multiple
studies have shown that the immunosuppressant
dose and depleting antibody agents used for
induction like anti-thymocyte globulin signifi-
cantly contribute to increasing UTI and risk for
other infections.5 The insertion of Foley’s
catheter is a routine practice during renal trans-
plantation surgery, which is a common cause of
UTI in the early post-transplantation period. As
the number of days with the urethral catheter in
situ increases, the risk of UTI increases. In the
general population, as the number of days with
the catheter in situ increases the risk of
bacteriuria increases by approximately 5% per
day.6 It is advisable to keep catheter for as short
as two days to prevent UTI.7
Meena P, Bhargava V, Rana DS, et al
Genetic Factors
Innate immunity is the first line of defense that
provides a barrier to pathogen invasion and is
responsible for host resistance against UTI.
Cells of innate immunity such as neutrophils,
macrophages, and natural killer cells, limit
penetration and damage by the pathogen.
Numerous studies have established the asso-
ciation of polymorphism in genes like toll-like
receptors (TLR4) and C-X-C Motif Chemokine
Receptor 1 (CXCR1) with asymptomatic bacte-
riuria (ASB) and acute pyelonephritis (APN).8
CXCR1 was the first identified human UTI
susceptibility locus, followed by polymorphisms
in other genes such as interferon regulatory
factor 3 and TLR4. Genetic variants lead to
impaired antibacterial defense by the host and
allowbacteria to establish infection in individual
hosts but not in others.9
Microbiological Factors
UTI in posttransplant patients can be caused
by viruses, bacteria, fungi and parasites. Gram-
negative bacteria, including Escherichia coli (E.
coli), Enterococcus sp., are the most common
organisms accounting for more than 70% of UTIs.
The strain of bacteria varies between centers as
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Urinary tract infection in renal transplant recipient
it depends on local epidemiology, immunosup-
pressive regimen, and antimicrobial protocol.
Pathogenicity of E. coli in urothelium increases
with P. fimbriae expressed on its surface to
facilitate its adherence to the urothelium.10
Patients with diabetes are predisposed to fungal
UTIs. Candida albicans is the most common
organism causing fungal UTIs. The fungus can
aggregate as fungal balls to obstruct and lead to
hydronephrosis.11 Common viruses causing UTIs
are the BK virus and cytomegalovirus (CMV)
virus. In countries like Africa, Schistosoma
hematobium is endemic. Its infection is often
associated with renal stones and ureteric
stricture.12 In developing countries, tuberculosis
(TB) mycobacteria is also a cause of UTI
(reactivated by immunosuppressive medication).
Allograft Factors
There is inconclusive evidence that as com-
pared to living kidney transplantation, trans-
plantation from deceased donors is at high risk
of postoperative UTI. The most likely cause of
lower incidence of UTI in kidneys from a living
donor could be due to shorter periods of cold
ischemia and less severe ischemia-reperfusion
as compared to cadaveric transplants.13 In
patients of autosomal dominant polycystic
kidneys, the native kidney serves as a reservoir
for microorganisms and can cause recurrent
UTI.
Some studies have found that because of the
use of more intense immunosuppression, acute
rejection (AR) episodes are linked to higher
episodes of UTIs.14
Ureteral Stents and Other Urinary Tract
Manipulations
History of instrumentation of the urinary tract
also predisposes transplant patients to UTI.15,16
Foreign material in the urinary tract, like stents
and Foley’s catheters can cause UTI. Loss of
glycosaminoglycans from the urothelium leads
to the invasion of pathogens into the cells of the
urothelium.17 Wilson et al have shown that
ureteric stents inserted during transplantation
309
surgery are associated with an increase in
relative risk of UTI up to 1.5-times.15 In a study
by Kamath et al, the odds ratio of ureteric stents
for UTI was as high as 4.6.18
AnatomicalFactors
In the renal transplant population, development
of urinary stasis due to urethral disease, pelvi-
ureteric obstruction, vesicoureteric junctions,
dysfunction of bladder or outflow obstruction,
and neurogenic bladder can lead to the develop-
ment of UTI. In renal transplantation surgeries,
the ureter is generally anastomosed to the
bladder by using an extravesical technique.19 In
this anastomosis, secondary reflux occurs,
which can affect both transplanted and native
kidneys. Unsterile infected urine, if present,
causes UTI and predisposes to graft pyelo-
nephritis.20 In the pediatric population disorders
like prune-belly syndrome, posterior urethral
valves, spina bifida, or any other urogenital
sinus abnormalities lead to any structural
changes or neurogenic bladder.21,22 Regular
posttransplant follow-up, and evaluation and
treatment of neurogenic bladder before kidney
transplantation is vital in these patients.23
Immunosuppression
Theoretically, the immunosuppression regimen
should impact UTI incidence and spectrum, but
there is insufficient evidence about the asso-
ciation of any specific immunosuppressant with
increased risk of UTI.24 However, anti-CD3 use
as induction treatment has been seen to increase
UTI incidence in numerous studies.25
Hence, multiple factors such as catheteri-
zation, manipulation of the urinary tract, lower
urinary tract dysfunction, and the impact of
antibody depleting agents are responsible for
UTI in the posttransplant period.
Clinical Presentation
As compared to the general population, trans-
plant patients with UTI are often asymptomatic
as symptoms and signs of UTI can be masked
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310
by immunosuppressive therapy. Especially pain
over the renal allograft is often absent because
of the denervated transplanted kidney.26
Symptomatic patients can present as acute
cystitis or graft pyelonephritis, sometimes with
native pyelonephritis. Symptoms depend on the
involvement of the upper urinary tract or lower
urinary tract, ranging from mild lower tract
irritative symptoms, for example, frequency,
urgency, dysuria, suprapubic tenderness, and
incontinence. However, there can be severe
systemic manifestations, such as bacteremia,
sepsis, and shock. Fever with costovertebral
angle pain and graft site tenderness are the
manifestations of APN. Sometimes, patients
can also complain of cloudy or foul-smelling
urine. Characteristic symptoms of UTI are
summarized in Table 1. A study by Valera et al2
on 172 transplant patients showed that uncom-
plicated acute bacterial cystitis is the most
common presentation and accounted for 77% of
UTIs. Another study on 189 renal transplant
patients reported APN in 10% of cases the
study showed that more than five episodes of
ASB after transplantation was as independent
predictors for APN.27 Infections with TB
manifest as low-grade prolonged fever and
renal impairment. BK virus infection can
present as symptomatic graft failure, urethral
stricture, and stenosis.26
Site of Infection
The most common site of involvement is the
urinary bladder (>95%), followed by renal allo-
graft. Occasionally, an infection of the native
kidneys can develop. Symptoms and signs of
UTI can be masked by immunosuppressive
therapy, especially pain over the graft is often
absent because of the denervated transplanted
kidney.26 Nevertheless, other atypical forms
Table 1. Symptoms of posttransplantation urinary tract infection
Lower urinary tract symptoms (cystitis)
Frequency
Urgency
Dysuria
Hematuria
Suprapubic pain
Meena P, Bhargava V, Rana DS, et al
must also be considered in a transplant
recipient. Prostatitis due to Cryptococcus,
Aspergillus, or Salmonella and epididymitis
with Klebsiella, Mycobacterium haemophilum,
CMV or TB have also been reported.28
Furthermore, orchitis due to salmonellosis and
CMV ureteritis have been described in the
context of renal transplantation.29 Recipients of
a combined pancreas-kidney transplant with
drainage of the exocrine pancreas to the bladder
might also develop (nonbacterial) urethritis.30
Pathogenesis
The pathogenesis of UTI typically begins with
uropathogenic bacteria ascending to the bladder
from the urethra. Pathologic invasion of the
urothelium is aided by bacterial virulence
structures, such as P. fimbriae, which promote
adhesion to the urothelium.31 Type 1 pili get
attached to mannose receptors on uroepithelial
cells lining the urinary tract.32 The absence of a
sphincter between the transplanted ureter and
the native bladder can predispose kidney trans-
plant recipients to develop transplant pyeloneph-
ritis. Transplant pyelonephritis can occasionally
occur by seeding of the kidney from blood-
stream infection or surgical site infection.33
Acute Effects of Urinary Tract Infection on
Graft Kidney
The acute effects of UTI on renal graft are
complex. Colonization of virulent microorga-
nisms in the renal pelvis can cause direct
cellular injury. Indirect damage can also occur
from inflammatory mediators. Sometimes metas-
tatic infection leads to renal infection, which
presents as cortical abscesses.34 Elevation of
inflammatory mediators and acute phase
reactants such as erythrocyte sedimentation rate
Upper urinary tract symptoms (pyelonephritis)
Rigors and/or pyrexia
Hematuria
Loin pain in the native kidney
Pain over graft
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Urinary tract infection in renal transplant recipient
and C-reactive protein (CRP) may be found.
Increased levels of serum interleukin-6 (IL-6)
and IL-8 are responsible for fever.35 The
secretion of tubular proteins in urine such as
α2-macroglobulin and N-acetyl-b-D-
glucosaminidase reflect tissue damage.
Bacteria can induce a serological immune
response to its various antigenic components
leading to damage to the renal parenchyma and
promote more permanent structural and
functional impairment.36
Asymptomatic Bacteriuria
Definition
The definition of ASB in patients without
indwelling catheters is ≥105 colony-forming
units (CFU)/mL in a voided urine specimen
without signs or symptoms attributable to
UTI.37 For women, two consecutive samples
should be obtained, within two weeks, to
confirm persistent bacteriuria. For men, a single
urine specimen meeting these quantitative
criteria is sufficient for diagnosis. Patients with
indwelling devices often have multiple
organisms isolated from the urine, some of
which are present at lower quantitative counts.38
ASB is a common finding in renal transplan-
tation patients. Risk factors for ASB are similar
to symptomatic UTI, such as female sex,
comorbidities, urologic abnormalities, and
immunosuppression. A retrospective analysis of
189 renal transplant patients on 36 months
follow-up showed that 51% of patients had one
or more episodes of ASB among these, 19% of
patients had one episode, 24% of patients had
2–5 episodes whereas 8% of patients had >5
episodes of ASB.27All episodes of bacteriuria in
these patients were consistently treated with
anti-microbials. More than two episodes of
ASB were reported as an independent risk
factor for APN. However, this finding was not
supported by other studies.39 In a study done by
Green et al analyzing a single episode of ASB
diagnosed in 112 patients following one year
after transplantation; antimicrobial treatment
for ASB was given to 19.6% of patients, no
difference was found in the increase in serum
311
creatinine, graft loss, pyelonephritis, or urosepsis
in treated and untreated patients.40 In various
other studies also no benefit of the treatment of
ASB was proved.34 Concern about the treatment
of ASB with antimicrobials is increasing the
risk of antimicrobial-resistant organisms, and
these resistant organisms are difficult to treat.41
There are high chances of promotion of re-
infection with organisms with the treatment of
ASB. High-quality evidence also suggests that
antimicrobial therapies are associated with
adverse effects.42
Recommendation
In renal transplant recipients who have had
renal transplant surgery >1 month prior, recom-
mendations are against screening or treating
ASB.37
Importance of First Three Months Post-
transplantation
Säemann and Hörl43 established that most
UTIs are diagnosed after renal transplantation
occurred within the first three months. A
retrospective cohort analysis involving 29,000
transplant patients reported a 17% cumulative
incidence of UTI during the initial three
months. So, it is essential to detect UTIs as
early as possible among transplant recipients,
particularly those who are within three months
of transplantation. According to Giral et al,
APN in the first three-month post-renal trans-
plant negatively affects graft survival.44
Diagnosis
History
Lower UTI present as burning micturition,
frequency, urgency, fever, allograft site pain,
and fatigue-like symptoms of systemic inflam-
mation. These are also common symptoms of
pyelonephritis. Careful clinical history is essen-
tial to distinguish between ASB and UTIs, more
importantly, APN.
Clinical examination
Patients presenting with UTI should be
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312 Meena P, Bhargava V, Rana DS, et al

examined for loin pain, suprapubic tenderness,
prostatomegaly, and atrophic vaginitis.
Specimen collection
As urine culture is crucial for the diagnosis of
UTI, accurate specimen collection is essential
to reduce the chances of contamination. A
specimen should be collected before the
administration of antibiotics. The Infectious
Diseases Society of America (IDSA) recom-
mends cleaning of perineum or glans with
antiseptic wipes and then collects mid-stream
clean catch urine in a sterile container.
Indwelling catheters increase the propensity of
colonizing flora due to biofilm formation;
therefore, specimens from urinary catheters in
place for >2 weeks are strongly discouraged,
but if necessary, the sample must be taken from
the sampling port of a newly inserted device.
The diagnostic recommendations by the IDSA
are presented in Table 2.
is the usual finding in UTIs. Its absence prompts
for consideration of an alternative diagnosis.45
The presence of a positive dipstick test for
leukocyte esterase and nitrite increases the
likelihood of a positive culture, but their
usefulness in renal transplant patients is limited.
The role of urine culture in the diagnosis of UTI
is indispensable. Typically, for symptomatic
UTI significant quantitative count of bacteria
(≥105 CFU/mL) is necessary. Definitions of
different UTIs according to urine culture are
given in Table 3.
In case of suspicion of pyelonephritis, blood
cultures should be sent before antibiotic
initiation. Raised CRP and leukocyte count
indicates systemic infection. To detect CMV
and BK virus, urine and blood polymerase
chain reaction and urine cytology for decoy
cells must be done. Suspected cases of TB
should be screened with the polymerase chain
reaction of early morning urine.

Laboratory testing
Pyuria (>10 white blood cells/mL in the urine)
Table 2. Classification of urinary tract infection in renal transplant recipients.
Type Clinical Appearance Urine
1. Acute uncomplicated lower Dysuria, urgency, frequency  >103 CFU/mL
UTI, cystitis (woman)  10 WBC/mm3
2. Acute, uncomplicated Fever, flank pain, no urologic  >104 CFU/mL
upper UTI: pyelonephritis abnormalities  10 WBC/mm3
3. Complicated UTI Symptoms from 1 to 2 plus at least 1  10 WBC/mm3
complicating factor:  >105 CFU/mL (female)
 Operative or radiotherapeutic changes  >104 CFU/mL (male)
of urinary tract
 Immune deficiency
 Ureter stent/bladder catheter
 Intermittent self-catheterization
 Diabetes mellitus
 Residual volume >100 mL
 Neurogenic bladder
 Vesicoureteral reflux
 BOO
4. Asymptomatic bacteriuria No urologic symptoms  >105 CFU/mL in 2 urine
samples >24 h apart
5. Recurrent, uncomplicated Only female 3 episodes of uncomplicated  >103 CFU/mL
UTI UTI/1 year; no structural or functional
pathology including both reinfections and
relapses
UTI: Urinary tract infection, CFU: Colony-forming units, WBC: White blood cell.
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Urinary tract infection in renal transplant recipient 313

Table 3. Diagnostic recommendations by the Infectious Diseases Society of America.

Type
Gram -ve bacteria
 Enterobacteriaceae:
includes Escherichia coli, low sensitivity)
Klebsiella spp
 Proteus spp
 Other Pseudomonas spp,
other nonfermenting gram-
negative rods
Gram +ve bacteria
 Enterococcus spp
 Staphylococcus aureus
 Staphylococcus
saprophyticus
 Corynebacterium
urealyticum
 Streptococcus agalactiae
(group B streptococci)
Mycobacteria
 Mycobacterium
tuberculosis
Virus Adenovirus
BK polyomavirus
Clinical symptoms Collection Urine
Routine aerobic culture Midstream, clean- Closed sterile leak-
Gram stain (optional, catch, or straight- proof container;
catch urine refrigerate (4°C) or use
urine transport tube
unless delivery to lab ≤1
h is certain
Routine aerobic culture Midstream, clean- Closed sterile leak proof
Gram stain (optional, catch, or straight- container; refrigerate
low sensitivity) catch urine (4°C) or use urine
transport tube unless
delivery to lab ≤1 h is
certain
Mycobacterial culture First-void urine Prefer >20 mL urine,
refrigerate (4°C) during
transport
NAAT Midstream or Closed sterile container
clean-catch urine to the lab within 1 h
Quantitative NAAT Serum or blood Serum EDTA or citrate
from urine, plasma blood collection tube,
RT Clot tube, RT

Imaging statement regarding posttransplant UTI prophy-

Role of different imaging modalities is as
follows:
 Ultrasound of transplanted kidney, native
kidney and bladder: Dilated pelvicocalyceal
system, stones
 Plain X-ray/computed tomography (CT)
kidney, ureter, and bladder: Stones in trans-
planted or native kidneys, pyelonephritis,
 CT–positron emission tomography:
Localized infection of polycystic kidneys,
 Micturatingcystogram: Suspected reflux,
 Urodynamics: Bladder dysfunction and
outflow obstruction,
 Static renogram (DMSA scan): Renal
scarring.
Prophylaxis and Challenges in Treatment of
Urinary Tract Infection
Although there is no consensual universal
laxis, however, most centers prescribe anti-
microbial therapy for three to six months but
follow variable regimens. Antimicrobial therapy
prophylaxis for the long term is effective in
reducing the incidence of UTIs, but its benefit
in the improvement of patient and graft survival
is not established. A meta-analysis by Green et
al showed that antimicrobial prophylaxis therapy
lowered the risk of developing bacteriuria by
60%. Trimethoprim/sulfamethoxazole (TMP/
SMX) was well tolerated, and a daily dose of
320/1600 mg provided optimal benefit.46 TMP/
SMX is the first-line recommended therapy for
prophylaxis against Pneumocystis jirovecii
pneumonia (PJP) for the first 6–12 months
posttransplant. In a prospective, double-blinded
randomized control trial by Khosroshahi et al,
done on 95 renal allograft recipients, two groups
were analyzed. Group 1 (n = 63) received low-
to-moderate doses of TMP/SMX (either 80/400
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314
mg or 160/800 mg, daily) and group 2 (n = 32),
high doses of TMP/SMX (320/1600 mg, daily
in two divided doses). The high dose group had
UTI in about 25% of patients, whereas UTI was
found in 49.2% in low- to moderate-dose
group.47 An increase in serum creatinine and
hyperkalemia are two important side effects of
TMP/SMX.
In numerous studies, fluoroquinolones were
also used as prophylaxis for renal transplant
recipients, but their use has been linked to
surges in fluoroquinolone-resistant Pseudomonas
aeruginosa. Other agents that can be used as an
alternative to TMP-SMX are nitrofurantoin
(only if estimated GFR >60 mL/min), cephalos-
porins (e.g., cephalexin) or fluoroquinolones.
Recommendations
TMP-SMX prophylaxis for six months is
recommended for PJP prophylaxis, and it
decreases UTI and bacteremia in renal allograft
recipients (evidence: strong, high).
If TMP-SMX cannot be used for primary
prophylaxis of UTI after renal transplant,
alternative agents with limited data include
nitrofurantoin (avoid if GFR <60 mL/min),
cephalexin, or fluoroquinolones.
For secondary prophylaxis of UTI in renal
allograft recipients with recurrent UTI, non-
antimicrobial prevention strategies are
preferred. Antimicrobial prophylaxis may be
appropriate for selected patients who have
severe episodes of recurrent UTIs such as
pyelonephritis (evidence: weak, low).
Ureteral Stent Removal
Ureteral stents are placed at ureteral-vesicular
anastomosis to prevent complications such as
urine leak, ureteral necrosis, and uretero-vesical
obstruction or stenosis.48 A Cochrane review
revealed that indwelling stents increase the risk
for UTI by 49%, but at the same time reduce
urological complications by as much as 76%. It
highlighted that indwelling stent increases UTI
risk if kept for >2 weeks.49
Meena P, Bhargava V, Rana DS, et al
Recommendations
In renal transplant recipients, limiting the
duration of catheters and stents to <4 weeks
following transplant surgery is suggested. If
severe UTI occurs in the period from two to
four weeks after the transplant, consider early
stent removal while balancing the risk of
urologic complications (evidence: strong,
moderate).50
Challenges in the treatment
Antibiotic-resistant micro-organism: With
unrestricted use of antibiotics in transplant
recipients, microorganism resistance to multiple
drugs has become the major concern in the
treatment of UTIs. The emergence of multi-
drug resistance (MDR), including organisms
producing extended-spectrum beta-lactamase or
carbapenemase, is associated with a poorer
outcome and increased risk of recurrent UTI.
Drugs such as colistin used may be nephro-
toxic and are associated with high mortality
rates.
Prolonged use of antibiotic therapy predis-
poses for fungal infections. Candiduria may
complicate UTI by forming a “fungus ball”
within the bladder and kidney.
Recommendations for Treatment of Urinary
Tract Infection in Post-Transplant Patients
For simple cystitis in renal allograft recipients,
it is reasonable to limit therapy to 5–10 days.
Single-dose or three-day treatment courses are
not recommended.
For pyelonephritis/complicated UTI in renal
allograft recipients, an antibiotic with narrow-
spectrum should be used to complete 14–21
days of therapy based on susceptibility data.
Short- and Long-term Outcome
The effect of UTI on graft survival in
transplant patients is still controversial. So far,
no consensus has been established about short-
term and long-term impact on UTI. Previously
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Urinary tract infection in renal transplant recipient
UTI was considered innocuous, but now there
are emerging shreds of evidence that UTI in
kidney transplant patients can cause severe
morbidity and increase in mortality affecting
long-term effects on graft function. Depending
on the pathogen virulence factor and its
interaction with host factors, it can result in
urosepsis, bacteremia, and devastating condition
of septic shock. In some studies, APN was not
associated with a decrease in graft or patient
survival, but as compared to patients with
uncomplicated UTIs, patients with APN are
found to exhibit an increase in serum creatinine
after one year that persisted four years after
transplantation.51 Papasotiriou et al analysis
showed no alteration in long-term renal
function with the occurrence of UTIs in
transplanted patients; nevertheless, APN may
be associated with an abiding decrease in renal
graft function.52 Other researchers have
confirmed that there are no differences in graft
survival rates between the patients without
UTIs and those who had a single episode;
however, a reduction of renal function might be
observed in patients during UTI episodes.18
Although there is a lack of literature regarding
the association of AR and UTI, few studies
report that UTI can trigger acute rejection
(AR).51,53 Intensive immunosuppressive treat-
ment of AR may predispose UTIs. A study by
Kamath et al proved this observation, and it
showed that AR preceded APN in 41% of cases
and APN episodes followed 28% of cases of
AR.18
The following are the impact of recurrent
UTIs on short and long-term outcomes after
renal transplantation:
1. APN
2. Recurrent hospitalization
3. Acute graft dysfunction
4. Chronic rejection
5. Urosepsis, bacteremia
6. Septicemia, death.
Future Areas for Investigation
There is a constant need for studies to
establish duration and drug of choice for
315
antimicrobial prophylaxis in renal allograft
recipients during this era of high prevalence of
MDR organisms.
New and reliable biomarkers are required to
confirm the diagnosis of UTI and distinguish
UTI from graft rejection. The optimal timing of
stent removal is yet to be explored. Treatment
and screening of ASB are still controversial.
Further RCTs are required to guide prophylaxis
and preventive therapies. Discovery of new
antibiotics with fewer side effect profiles is
required. Research of non antibiotic and vaccine
approaches to the prevention of recurrent UTI is
warranted and recommended. An appropriate
immunosuppressive regimen/protocol to reduce
the incidence of UTI should be developed.
Conflicts of interest: None declared
References
1. Gondos AS, Al-Moyed KA, Al-Robasi AB, Al-
Shamahy HA, Alyousefi NA. Urinary tract
infection among renal transplant recipients in
Yemen. PLoS One 2015;10:e0144266.
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