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CEN Case Reports
Official Publication of the Japanese
Society of Nephrology
e-ISSN 2192-4449
CEN Case Rep
DOI 10.1007/s13730-017-0301-2
Renal vein thrombosis complicating severe
acute pyelonephritis with renal abscesses
and associated bacteraemia caused
by extended-spectrum beta-lactamase
producing Escherichia coli
Stelios F.Assimakopoulos, Pantelis
Kraniotis, Charalambos Gogos &
Markos Marangos
1 23
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Vol.:(0123456789)
1 3
CEN Case Reports
https://doi.org/10.1007/s13730-017-0301-2
CASE REPORT
Renal vein thrombosis complicating severe acute pyelonephritis
withrenal abscesses andassociated bacteraemia caused byextended-
spectrum beta-lactamase producing Escherichia coli
SteliosF.Assimakopoulos1· PantelisKraniotis2· CharalambosGogos1· MarkosMarangos1
Received: 5 November 2017 / Accepted: 27 December 2017
© Japanese Society of Nephrology 2018
Abstract
Acute pyelonephritis might be complicated by the formation of renal and perirenal abscesses and very rarely by renal vein
thrombosis, which is a life-threatening condition. The main causative agents of acute pyelonephritis are enterobacteriaceae
with the incidence of extended-spectrum beta-lactamase (ESBL)-producing strains increasing worldwide. We present the case
of a 71-year-old Greek man with history of diabetes mellitus and recent hospitalization, who suffered from severe pyelone-
phritis with renal abscesses formation and associated bacteraemia caused by ESBL-producing Escherichia coli, complicated
by extensive thrombosis of the ipsilateral renal vein and its branches, protruding also in the inferior venal cava. Our patient
was effectively treated with anticoagulants and targeted antibiotic therapy, respectively, consisted of low molecular weight
heparin transitioned to oral acenocoumarol for 3months and 2-week course of intravenous meropenem followed by oral
fosfomycin for additional 3weeks as quidded by clinical and computed tomographic follow-up. In conclusion, in complicated
urinary infections, caused by ESBL-producing enterobacteriaceae, oral fosfomycin might represent an effective option for
step-down therapy of carbapenems, allowing the shortness of the duration of patient’s hospitalization and carbapenem use.
Keywords Urinary tract infections· Renal abscess· Renal vein thrombosis· Extended-spectrum beta-lactamase· ESBL·
Fosfomycin
Introduction
Renal vein thrombosis is a very rare and life-threatening
complication of acute pyelonephritis [1]. To our knowledge,
only seven cases of RVT complicating acute pyelonephritis
have been described in the literature [1]. The main patho-
gen implicated as a causative agent in renal abscesses is by
far Escherichia coli (E. coli), while there is a continuously
increasing prevalence of community-acquired urinary infec-
tions caused by extended-spectrum beta-lactamase (ESBL)-
producing enterobacteriaceae [2, 3]. We describe herein, a
case of severe pyelonephritis with the formation of multiple
renal abscesses and bacteraemia, due to ESBL-producing E.
coli, complicated by extensive thrombosis of the ipsilateral
renal vein and its branches, protruding also in the inferior
venal cava.
Case report
A 71-year-old man with a past medical history of diabetes
mellitus type II and recent hospitalization (2months ago),
for surgical repair of right scrotal hernia, presented fever
(39.5°C) with rigors and dysuria 2weeks before admis-
sion to our clinic. Urinalysis showed pyuria, bacteriuria
and nitrites presence, and ciprofloxacin 500mg bid was
empirically administered by his urologist. Urine culture
grew E. coli resistant to b-lactams including aztreonam,
b-lactam/b-lactamase inhibitors (piperacillin–tazobactam
MIC > 16/4 μg/ml), fluoroquinolones, trimethoprim/sul-
famethoxazole and sensitive to aminoglycosides amikacin
and netilmicin, carbapenems and colimycin. Ciprofloxacin
was discontinued and amikacin was prescribed 1g once a
* Stelios F. Assimakopoulos
sassim@upatras.gr
1 Division ofInfectious Diseases, Department ofInternal
Medicine, University General Hospital ofPatras,
26504Patras, Greece
2 Department ofRadiology, University General Hospital
ofPatras, 26504Patras, Greece
Author's personal copy
CEN Case Reports
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day intramuscularly with gradual clinical improvement and
resolution of fever the fourth day of treatment. However, due
to increase in creatinine values from 1.0mg/dL pre-treat-
ment to 2.1mg/dL the seventh day of treatment, amikacin
was discontinued. 4days later patient’s symptoms relapsed
with fever 39.5°C with rigors, anorexia, nausea and flank
pain and the next day he was referred to our hospital for fur-
ther evaluation and treatment. Physical examination revealed
a shivering man with 39.5°C of temperature, blood pressure
130/70mm Hg, pulse rate 110 beats per minute, respiratory
rate 14 breaths per minute with an oxygen saturation of 98%
on room air. He weighed 74kg with a BMI of 25.6kg/m2
and a height of 170cm. Right costovertebral angle tender-
ness (Giordano sign) was observed on palpation. The physi-
cal examination was otherwise unremarkable. Blood tests
showed leucocytosis (19.300/mm3 with 87% polymorpho-
nuclear predominance), normal hemoglobin levels 13.6g/dL
and platelets count of 337.000/μL. CRP levels were elevated
at 28.5IU/L (normal value < 0.5IU/L). Biochemical tests
revealed hyperglycaemia of 380mg/dL (without diabetic
ketoacidosis), normal levels of aminotransferases, direct
and indirect bilirubin and lactate dehydrogenase, while also
renal function had returned to normal with creatinine levels
of 1.1mg/dL and urea 36mg/dL. Prothrombin and partial
thromboplastin times were normal, d-dimers were increased
at 2.49μg/ml and fibrinogen was also increased at 613mg/
dL. Urinalysis showed greater than 100 white blood cells
and 100 bacteria per high-power field, microscopic haema-
turia with 30–40 red blood cells per high-power field and
presence of nitrates. Urine and blood cultures grew E. coli
with the same antibiogram as reported in the patient’s pre-
hospital evaluation. Initial imaging evaluation of the right
kidney and ureter with ultrasonography did not show evi-
dence of urinary flow obstruction but multiple hypoechoic
cystic lesions with inner diaphragms were detected in the
right renal parenchyma. Further imaging evaluation with
abdominal computed tomography (CT scan) with intrave-
nous iodine contrast medium showed extensive thrombosis
of the right renal vein and its branches protruding to the
inferior vena cava (Fig.1a) and right kidney pyelonephritis
with multiple renal abscesses the largest exhibiting a diam-
eter of 2.1cm (Fig.1b). Thrombophilia screening including
protein S, protein C, antithrombin deficiency, factor V Lei-
den, prothrombin 20210A and MTHFR (C677T) mutations,
homocysteine plasma level, paroxysmal nocturnal hemoglo-
binuria flow cytometry flair, antiphospholipid antibodies,
lupus anticoagulant, anti-cardiolipin and b2 glycoprotein-1
autoantibodies turned out negative.
The patient was treated with intravenous meropenem
2g (in 3-h intravenous infusion) every 8h and antico-
agulation with low molecular weight heparin, which was
transitioned to oral acenocoumarol. The patient became
asymptomatic and afebrile the fourth day of his hospitali-
zation with gradual reduction of inflammatory markers. A
repeated CT imaging performed 10days after the initial
CT, showed reduction of renal abscesses dimensions, which
were measured up to 1.5cm in their maximum diameter
as compared to 2.1cm at the initial imaging. Intravenous
Fig. 1 a, c, e Volume-rendered coronal reformatted CT images. Renal
parenchymal phase post IV contrast. Imaging at patient’s initial pres-
entation (a), at 5-week interval of antibiotic and anticoagulant treat-
ment (c), and at 12-week interval of anticoagulant therapy (e). b, d,
f Minimum intensity projection (MinIP) reformatted images. Renal
parenchymal phase post IV contrast at presentation (b), at 5weeks
(d), and at 12weeks (f). a There is thrombus within the right renal
vein (arrow) and its branches (arrowhead). The thrombus is protrud-
ing in the inferior vena cava (asterisk). b Two of the largest abscesses
are depicted in the right kidney (arrows). c There is no thrombus in
the right renal vein and its branches. However, a small residual com-
ponent still exists in the inferior vena cava (asterisk). d There are only
small residual changes (arrows), in the corresponding positions of the
abscesses depicted in b, consistent with the formation of scar tissue,
5 weeks after treatment. There is no appreciable interval change in
the lower pole renal cyst, on the right. e The residual inferior vena
cava thrombus seen in previous image is now imperceptible (cycle). f
A typical scar is left in the renal parenchyma (arrow)
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CEN Case Reports
1 3
meropenem was administered for a total of 14days. The
patient was discharged on oral fosfomycin 3g once daily for
3days followed by every-other-day 3g dosing and aceno-
coumarol with an INR target of 2.5 (2.0–3.0). On this treat-
ment, the patient remained asymptomatic and afebrile and
a repeated retroperitoneal CT performed 3weeks after his
hospital discharge demonstrated that the extensive right
renal vein thrombosis had completely resolved and only a
small residual thrombus had remained in the inferior vena
cava (Fig.1c). The renal abscesses had also resolved with
only small residual changes, consistent with the formation
of scar tissue (Fig.1d). Oral fosfomycin was discontinued
and acenocoumarol was administered for additional 7weeks
(total duration of anticoagulation 3months as provoked deep
venous thrombosis). A follow-up CT performed at 3months
after the initial CT imaging, showed that the residual infe-
rior vena cava thrombus seen in the previous CT had been
totally resolved (Fig.1e), while a typical scar was left in the
renal parenchyma (Fig.1f). To date, 2years later, no relapse
of the patient’s pyelonephritis/renal abscess and renal vein
thrombosis has occurred.
Discussion
Renal vein thrombosis occurs mainly due to systemic hyper-
coagulable states, the most common being nephrotic syn-
drome with urinary losses of anticoagulant proteins [4].
Other prothrombotic aetiologies of renal vein thrombosis
include hyperhomocysteinemia, antiphospholipid syndrome,
paroxysmal nocturnal hemoglobinuria, renal cell carcinoma
or other active malignancy, renal transplantation, trauma,
postpartum, oral contraceptive use and sepsis syndrome
[5–10]. Only seven previous cases of RVT complicating
acute pyelonephritis or renal and perirenal abscesses have
been described [1].
The potential mechanism of renal vein thrombosis in the
presented bacteremic patient might be an endotoxin-induced
procoagulant state. Endotoxin, a lipopolysaccharide found
in the cell wall of Gram-negative bacteria, might promote a
prothrombotic state through changes in the endothelial sur-
face, by increasing the expression of the gene encoding tis-
sue factor (procoagulant molecule) and by rising endothelial
cell production of the fibrinolytic inhibitor plasminogen acti-
vator inhibitor-1 [11]. A mechanism of disseminated intra-
vascular coagulation in the context of our patient’s serious
infection is not supported by laboratory findings because
there was no thrombocytopenia or increased markers of
haemolysis (indirect bilirubin and lactate dehydrogenase),
coagulation parameters were not prolonged and fibrinogen
was not decreased.
The therapeutic approach to our patient was directed
towards two parallel directions; anticoagulant treatment for
renal vein thrombosis and effective antimicrobial therapy
of the ESBL-producing E. coli-induced renal infection and
bacteraemia. Since no underlying thrombophilic condition
was found, we considered that renal vein thrombosis was
provoked in our patient by his serious acute pyelonephritis
and renal abscesses. Low molecular weight heparin with
subsequent oral anticoagulation for 3months, as commonly
used in other provoked thromboembolic states, proved to be
an effective treatment, as also demonstrated in other reported
similar cases of renal vein thrombosis complicating renal
infection [1, 12].
The causative agent of our patient’s renal infection and
bacteraemia was demonstrated to be an ESBL-producing
E. coli strain. ESBL are enzymes that confer resistance to
most beta-lactam antibiotics, including penicillins, cephalo-
sporins and the monobactam aztreonam, while emergence
of plasmid-mediated quinolone resistance in ESBL-produc-
ing isolates has become a global problem for treating these
infections [2]. Despite sensitivity of our patient’s pathogen
to aminoglycosides, induction of renal toxicity excluded
this therapeutic option. In this context, carbapenem use
was reasonable and almost inevitable. Alternative to car-
bapenems options include the beta-lactam/beta-lactamase
inhibitor combinations of piperacillin–tazobactam, ceftolo-
zane–tazobactam and ceftazidime–avibactam [13]. The last
two options were not available in Greece when this case
occurred, while piperacillin–tazobactam was not used owing
to increased MIC (> 16/4μg/mL) [13, 14].
Renal abscesses < 5cm in diameter, are initially treated
with antimicrobial therapy alone (without drainage) [15].
In case of clinical response, the intravenous antimicrobial
treatment is instituted for 2weeks followed by oral step-
down therapy, which is extended for at least two additional
weeks, depending on the results of radiographic follow-up
[16]. However, in the case of ESBL-associated upper urinary
tract infections, the selection of oral step-down therapies is
problematic, because these pathogens are commonly resist-
ant to available oral options such as amoxycillin/clavula-
nate, oral cephalosporins, trimethoprim–sulfamethoxazole
and fluoroquinolones.
Fosfomycin is an old agent that remains active against
ESBL-producing E. coli strains, but it is currently only
approved for a 3g single-dose treatment of uncomplicated
lower urinary tract infections. Two sequential studies, the
PROOF and FOCUS, are being implemented and planned,
respectively, to test the optimal dosing and the efficacy of
fosfomycin over levofloxacin as oral step-down therapy in
complicated urinary tract infections including pyelonephri-
tis [3]. Pending these results, in our patient, we selected to
give three consecutive daily oral doses of 3g fosfomycin
as a loading scheme, followed by every-other-day 3g dos-
ing for additional 3weeks. This treatment schedule was
proven an effective carbapenem step-down oral therapy,
Author's personal copy
CEN Case Reports
1 3
as demonstrated by the complete resolution of clinical and
radiological signs of renal infection and by the absence of
relapse during follow-up.
In conclusion, we presented a rare case of extensive renal
vein thrombosis complicating severe pyelonephritis with
multiple abscesses formation and associated bacteraemia,
caused by an ESBL-producing strain of E. coli. Our patient
was effectively treated with anticoagulants, low molecular
heparin transitioned to acenocoumarol, for 3months and
targeted antibiotic therapy consisted of 2-week course of
intravenous meropenem followed by oral fosfomycin for
additional 3weeks as quidded by clinical and computed
tomographic follow-up. In complicated urinary infections,
caused by ESBL-producing enterobacteriaceae, oral fosfo-
mycin might represent an effective option for oral step-down
therapy of carbapenems, but results from randomized clini-
cal studies are needed.
Compliance with ethical standards
Conflict of interest The authors have declared that no conflict of inter-
est exists.
Human rights This article does not contain any studies with human
participants performed by any of the authors.
Informed consent Informed consent was obtained from all individual
participants included in the study.
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