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Received for publication: 31.3.2011; Accepted in revised form:
30.10.2011
Nephrol Dial Transplant (2012) 27: 3488–3493
doi: 10.1093/ndt/gfr810
Advance Access publication 17 February 2012
Cristiana Rollino1, Giulietta Beltrame1, Michela Ferro1, Giacomo Quattrocchio1, Manuela Sandrone2
and Francesco Quarello1
1
Department of Nephrology and Dialysis, San Giovanni Bosco Hospital, Turin, Italy and 2Department of Radiology, San Giovanni
Bosco Hospital, Turin, Italy
Correspondence and offprint requests to: Cristiana Rollino; E-mail: [email protected]
Abstract
Background. Acute pyelonephritis (APN) is a common
disease which rarely evolves into abscesses.
Methods. We prospectively collected clinical, biochemical and radiological data of patients hospitalized with a
diagnosis of APN from 2000 to 2008.
Results. Urinary culture was positive in 64/208 patients
(30.7%) and blood cultures in 39/182 cases (21.4%). Two
hundred and thirteen patients were submitted to computed
tomography (CT) or nuclear magnetic resonance (NMR):
confirmation of APN was obtained in 196 patients (92%).
Among these, 46 (23.5%) had positive urine culture, 31
(15.8%) had positive blood culture and 15 (7.6%) had
positive cultures of both urine and blood. In 98 patients,
either urine or blood cultures were negative, but CT/NMR
were positive for APN. Fifty of the 213 patients submitted
to CT/NMR (23.5%) had intrarenal abscesses: only 2
were evidenced by ultrasound examination. No differences were found between patients with positive or negative CT with regards to fever, leucocytosis, C-reactive
protein, pyuria, urine cultures and duration of symptoms
before hospitalization. No differences were found between
patients with or without abscesses with regards to these
parameters and risk factors. Patients with abscesses had a
longer duration of treatment and hospitalization.
Conclusions. Our data suggest that in APN it is not
always possible to routinely document urinary infection in
a clinical setting. This finding could be explained by previous antibiotic treatment, low bacterial growth or atypical
pathogens. Systematic CT or NMR is necessary to
exclude evolution into abscesses, which cannot be suspected on clinical grounds or by ultrasound examination
and may also develop in the absence of risk factors.
Keywords: acute pyelonephritis; renal abscess; urinary tract infection
Introduction
Acute pyelonephritis (APN) in the USA has an incidence
as high as 250 000 cases per year and requires 100 000
hospitalizations every year [1].
Women are affected five times more frequently than
men but have a lower mortality (7.3 versus 16.5 death/
1000 cases) [1]. Evolution into abscess is considered
infrequent.
APN develops when uropathogens, mainly Escherichia
coli [2], ascend to the kidneys from faecal flora; rarely, it
is caused by seeding of the kidneys by bacteraemia. Risk
factors include frequency of sexual intercourse, genetic
predisposition, old age, urinary instrumentation, diabetes
and urinary tract infections in the previous months [3].
The exact correlation between APN and vesicoureteral
reflux (VUR) in adults is not clearly defined.
Diagnosis of APN is mainly clinical, but computed
tomography (CT) or nuclear magnetic resonance (NMR)
examination allows precise definition of the inflammatory
areas [4, 5] and evidence of abscesses.
We conducted a prospective analysis of the cases of
APN hospitalized in the Nephrology Unit from January
2000 to August 2008.
Materials and methods
We prospectively recorded all patients hospitalized in our Nephrology
Department from January 2000 to August 2008 with a diagnosis of APN
© The Author 2012. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
For Permissions, please e-mail: [email protected]
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Acute pyelonephritis in adults: a case series of 223 patients
APN in adults: a case series
made by the Emergency Department and based on the presence of flank
pain, fever and leucocytosis or elevated C-reactive protein (CRP).
Spiral CT with contrast medium and/or NMR (since 2006) was performed in all patients. In patients with abscesses, a second CT was done
after 30 days.
Retrograde urethrocystography to search for VUR was performed in
case of relapsing APN or in the presence of anatomical urinary
abnormalities.
Treatment consisted of ceftriaxone 2 g/day for 5 days intravenously,
followed by ciprofloxacin 500 mg twice daily orally for 14 days, except
for patients allergic to these antibiotics and in the case of resistant bacteria. When no response was observed after 72 h, treatment was modulated on the basis of antibiotic sensitivity testing. Patients with abscesses
were treated with ceftriaxone 2 g daily for 30 days. Patients <18 years of
age were given oral cephalosporin instead of fluoroquinolones.
The general practitioner was charged with the follow-up of the
patients after hospitalization.
Definitions
Statistical analysis
Values are expressed as mean ± SD. Statistical analysis was conducted
with Student’s t or χ2 tests.
Results
We collected the records of 223 patients (202 women, 21
men, mean age 37.77 ± 17.61 years; mean age of women
was 36.56 ± 0.53, of men 49.43 ± 18.60). Distribution of
patients in age groups is reported in Figure 1.
Clinical presentation is reported in Table 1.
Leucocytosis was evident in 183 patients (82.06%);
mean leucocytes of these patients were 16 960 ± 5869/
mm3. Leucocytosis normalized in 4.21 ± 3.73 days. Mean
Fig. 1. Distribution of patients for decades of age.
CRP was 15.65 ± 8.56 mg/dL. Pyuria was present in 147
patients (65.92%).
Renal function was normal in all but 21 patients,
whose serum creatinine was >1.2 mg/dL (in these patients
glomerular filtration rate ranged from 8 to 47 mL/min/
1.73m2 according to Modification of Diet in Renal
Disease formula [6]). In 13 of these patients, renal failure
was attributed to the multiple effects of the infection
(direct and haemodynamic). In one patient, there was an
important diffuse interstitial neutrophilic infiltration evidenced by renal biopsy; this patient transiently required
dialysis.
Risk factors were present in 60 patients (26.9%)
(Table 2).
The duration of hospitalization was 11 ± 11 days.
Urine cultures were available for 208 patients: 64/208
were positive (30.7%) (E. coli 56 patients, Klebsiella
pneumoniae 4 patients, Enterococcus faecalis 1 patient,
Proteus mirabilis 2 patients, K.pneumoniae plus E.faecalis
1 patient). Blood cultures were positive in 39/182 cases
(21.4%): E. coli 35 patients, Acinetobacter lwoffii 1
patient, P.mirabilis 1 patient, Streptococcus saprophyticus
1 patient and Staphylococcus hominis 1 patient.
Sensitivity of E. coli to ceftriaxone was 100%, to ciprofloxacin 85.3% and to levofloxacina 85.7%.
Both urine and blood cultures were available for 171
patients (76.6%). They were both positive in 19 of these
patients (11.1%). In 34/171 (19.8%), urine cultures were
positive and blood cultures negative; in 20/171 (11.6%),
blood cultures were positive and urine cultures negative.
Concordance between blood and urine cultures was
68.42%.
Renal ultrasound examination was performed in 209/
223 patients (93.7%). It was normal in 109 cases (52.1%)
and suggestive of APN in 100 cases (47.8%). In these
cases, single or multiple hyperechogenic areas (51
patients), kidney enlargement (16 patients), thickening of
pelvic wall (6 patients), hypoechogenic areas (20
patients), pelvic dilation (13 patients), perirenal fat involvement (5 patients) and abscesses (2 patients) were
evidenced.
Downloaded from http://ndt.oxfordjournals.org/ at University of Auckland on September 4, 2012
‘Old age’ refers to people >65 years of age.
Fever was considered when ear temperature was >37.5°C.
Pyuria was defined as >10 white blood cell (WBC)/h.p.f.; leucocytosis as >9500 WBC/mm3; urinary cultures were considered positive if
>103 colony-forming units (c.f.u/mL) of bacteria were found.
CT was considered diagnostic for APN if single or multiple hypodense parenchymal areas were evidenced after contrast medium infusion.
In NMR, APN areas correspond to hypointense areas in T1 after gadolinium medium infusion (Gadovist—Bayer Schering Pharma).
APNs were considered complicated when they occurred in pregnant
women, old patients, transplanted patients, patients with diabetes,
bladder catheters or urinary stones.
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C. Rollino et al.
Table 1. Characteristics of the patients
Patients (N)
Female/male
Right/left kidney
Mean age (years)
Duration of symptoms before hospitalization (days)
Mean ear temperature (°C)
Duration of fever (days)
Leucocytosis (N of patients)
Mean leucocytes (/mm3)
Mean CRP (mg/dL)
Positive urine culture (N)
Positive blood culture (N)
Both urine and blood positive culture (N)
Pyuria (N)
Risk factors (N of patients)
Presence of renal failure
Days of hospitalization
223
202/21
1.5
37.77 ± 17.61
5.79 ± 11.15
39.18 ± 0.79
5.34 ± 6.85
183 (82.06%)
16 960 ± 5869
15.65 ± 8.56
64/208 (30.7%)
39/182 (21.4%)
19/171 (11.1%)
147/223 (65.92%)
60/223 (26.9%)
21/223 (9.4%)
11 ± 11
Diabetes
Pregnancy
Renal transplant
Recent hospitalization (by 3 months)
Kidney stones
Vesico-ureterale reflux
Anatomical defects (ureteral duplication, ureteropyelic junction
stenosis, renal ectopia)
Neurological bladder
New bladder after cystectomy
Prostatitis
Self-catheterization
Endocarditis
Balanoposthitis
Actinic cystitis
Permanent catheter
a
Risk factors: number of patients.
Fig. 2. Spiral CT: multiple areas of APN in the left kidney.
14
2
6
11
13
9
5
3
3
2
2
1
1
1
1
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Table 2. Characteristics of the patientsa
CT scan was performed on 183/223 (82.06%) patients.
It was normal in 12 cases (6.5%); it showed lesions suggestive for APN in 170/183 cases (92.8%), with evidence
of single or multiple areas of parenchymal hypodensity
(Figure 2). Concordance between CT scan and ultrasound
was 49%.
NMR was performed in 57 cases (47 positive and 10
negative). Among the 170 patients with positive CT, 26
were also evaluated with NMR, which resulted positive in
21 and negative in 5. In one case, NMR showed an
abscess which had not been documented by CT. Thirty
patients were submitted to NMR only: this examination
documented APN in 25 patients.
In total, 213 patients were submitted for CT and/or
NMR (95.5%). A radiological confirmation of APN by
CT and/or NMR was obtained in 196/223 (87.9%)
patients with symptoms typical for APN. Among these
patients, only 46 (23.5%) had positive urine culture, 31
(15.3%) had positive blood culture and 15 (7.6%) had
positive cultures of both urine and blood. In 98 patients,
urine or blood cultures were negative, but TC/NMR was
positive for APN. In the 12 patients with normal CT,
blood or urine cultures were positive.
No differences were found between patients with positive or negative CT or NMR with regard to body temperature at admission, leucocytosis, CRP and duration of
symptoms before hospitalization (Table 3). Urine and
blood cultures were positive more frequently in patients
with negative CT/NMR (Table 4).
Fifty of the 213 patients submitted to CT/NMR
(23.5%) had single or multiple intrarenal abscesses
(Figure 3). Ultrasound examination evidenced abscesses
in only two patients. No differences were found between
patients with or without abscesses with regards to body
temperature, leucocytosis, duration of fever, duration of
symptoms before hospitalization, CRP pyuria and urine
cultures (Table 5). Patients with abscesses were
APN in adults: a case series
3491
Table 3. Comparison between positive and negative CT/NMR patients
Leucocytes (/mm3)
CRP (mg/dL)
Duration of symptoms before hospitalization (days)
Temperature (°C)
a
a
CT/NMR negative
CT/NMR positive
Significance
18 290.59 ± 12 216.05
12.22 ± 80.6
10.63 ± 21.11
39.17 ± 0.94
15 209.19 ± 5777.37
16.09 ± 8.63
5.45 ± 10.10
39.21 ± 0.78
n.s. (P 0.06)
n.s. (P 0.08)
n.s. (P 0.08)
n.s. (P 0.85)
n.s., not significant.
Table 4. Comparison between positive and negative CT/NMR patients concerning urine and blood culturea
CT/NMR positive
Significance, P
10/17 (58.8%)
8/11 (72.7%)
11/13 (84.6%)
46/183 (25.1%)
30/165 (18.1%)
59/192 (30.7%)
0.0033
0.000001
0.0001
a
The data express the number of positive urine and/or blood culture out of the number of cultures obtained in the subgroups of CT/NMR negative or
positive patients. Note that negative CT/NMR patients were more frequently found to have positive cultures.
Fig. 3. Abscess in the right kidney at spiral CT.
Table 5. Comparison between patients with and without abscessesa
Positive urine culture
Pyuria (presence)
Leucocytosis (N/mm3)
CRP (mg/dL)
Temperature (°C)
Days of fever
Days of hospitalization
Duration of symptoms before hospitalization (days)
Abscess absence
Abscess presence
Significance
47/149 (31.5%)
102/153 (66.6%)
14 979.67 ± 6434.85
16.06 ± 8.48
39.16 ± 0.81
5.44 ± 7.52
8.63 ± 9.67
6.23 ± 12.69
10/50 (20%)
30/48 (62.5%)
16 912.72 ± 6676.36
14.87 ± 9.09
39.38 ± 0.66
5.48 ± 4.23
16.68 ± 14.15
4.51 ± 4.16
n.s. (P 0.07)
n.s. (P 0.59)
n.s. (P 0.11)
n.s. (P 0.4)
n.s. (P 0.12)
n.s. (P 0.98)
P 0.000008
n.s. (P 0.35)
a
The data express the number of positive urine and/or blood culture out of the number of cultures obtained in the subgroups of patients with and
without abscesses. n.s., not significant.
Downloaded from http://ndt.oxfordjournals.org/ at University of Auckland on September 4, 2012
Positive urine culture
Positive blood culture
Urine and blood positive culture
CT/NMR negative
3492
hospitalized for a longer time (16.68 ± 14.15 versus 8.63
± 9.67 days) and were treated for longer (33.06 ± 10.29
versus 19.56 ± 4.7 days) (Table 5).
In the 43 patients in whom retrograde urethrocystography was performed, VUR was found in 9 patients
(20.9%).
Outcome
Contrast medium for CT induced a transient increase in
serum creatinine in the patients with renal failure; creatinine returned to previous values in all cases afterwards.
VUR. Among the patients with VUR, which was thereafter corrected with endoscopic procedure, three
patients presented relapses of the urinary infection. One
had an evolution towards renal failure (chronic kidney
disease Class IV after 5 years) and the others remained
with normal renal function.
Abscesses. In all the patients with abscesses, a second
CT for control performed at 1 month demonstrated the
disappearance of the abscesses.
Discussion
Our interest in APN originated from the observation of
the increasing frequency of this disease and from the uncertain indications in the literature with regard to the opportunity of performing CT/NMR. Moreover, we noted
that not all our patients had positive urine culture.
Hence, since 2000, we prospectively collected data of
patients admitted in the Nephrology Unit with a diagnosis
of APN made by the Emergency Department; 95.5% of
them were submitted to CT scan or NMR (since 2006,
when it became available in our hospital) or both.
The most significant data resulting from our study are
that only 23.5% of patients with diagnosis of APN confirmed by either CT scan or NMR had positive urine
culture (Table 4) and that 23.5% of the 213 patients submitted to CT/NMR had single or multiple intrarenal abscesses (Figure 3).
The low frequency of positive urine culture may be explained by previous antibiotic treatment, either self-prescribed or prescribed by the general practitioner, and by
the possibility that infection was confined to the renal parenchyma. Moreover, atypical organisms, such as Ureaplasma urealyticum (responsible for 4.8% of APN cases
[7]) and Mycoplasma hominis, which are not found
unless particular culture media containing arginine and
urea are used, were not searched.
Also, pyuria was found in only 65.92% of our patients.
Even though these data seem in contrast with the standard definition of APN, which includes bacterial growth of
at least 10 000 c.f.u/mL in presence of symptoms [2, 5, 8],
they reflect the common medical practice in a big hospital
(326 beds for hospitalization) in a town of northern Italy.
Twelve patients had negative CT but typical symptoms
and positive urine cultures. The explanation for this could
be that the inflammatory lesions had already improved
when the patients were submitted to radiological examination or that they were so mild as to be undetectable.
Another crucial point is the frequent finding of abscesses
evidenced in 23.5% of cases by CT/NMR (Figure 3).
Treatment of the smallest abscesses may be medical
[9], but surgical drainage is needed in the case of size >5
cm [9, 10]. Longer duration of antibiotic therapy is also
advised [11].
No elements allowed a clinical differentiation of
patients with or without abscesses (Table 5). We think
that this finding strengthens the indication to perform CT
or NMR systematically in patients with APN since detection of abscesses can modify therapeutic approach.
While the association between APN and VUR has been
extensively studied in children [12, 13], the literature does
not indicate when VUR must be searched in adults.
We performed retrograde urethrocystography in the
case of recurrent APN or in the presence of urinary cavities dilation or urinary tract abnormalities: we found
VUR in 20.9% of patients. They were successfully treated
with endoscopic procedure and only one of them had relapsing APN.
In our opinion, the most significant elements in the
recent literature regarding APN are the revised guidelines
for treatment [14]: in this paper, Gupta underlines the
need of differentiating patients requiring hospitalization or
not. Cases with less severe forms can be treated with ciprofloxacin for 7 days, levofloxacin 750 mg once per day
for 5 days or trimethoprim/sulphametoxazole for 14 days
if the sensitivity is known. More severe cases should be
initially treated with an intravenous regimen (a fluoroquinolone, an aminoglycoside with or without ampicillin, an
extended spectrum cephalosporin with or without aminoglycoside or a carbapenem). Much concern regards antibiotic resistance [14, 15], which must be monitored.
In conclusion, the absence of infected urine does not
rule out the diagnosis of APN in common clinical practice. Renal abscesses are frequent and may not be suspected on a clinical basis. Hence, it seems advisable to
systematically perform CT or NMR, which have greater
sensitivity than ultrasound in detecting them.
Conflict of interest statement. None declared.
(See related article by Abraham et al. Diagnosis of acute pyelonephritis
with recent trends in management. Nephrol Dial Transplant 2012; 27:
3391–3394.)
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Downloaded from http://ndt.oxfordjournals.org/ at University of Auckland on September 4, 2012
The cure rate was 100%.
Recurrences. Thirty-six patients had relapses. In four
cases, multiple episodes were observed. The time
elapsed from the first episode to the first recurrence
ranged from 2 months to 12 years.
Renal function. The 21 patients with renal failure were
older than the others of this series (median was
64 years). Among them, 13 had a complete recovery of
renal function, 1 remained stable, 1 improved but did
not normalize (the patients who had required dialysis)
and 1 progressed to end-stage renal disease. The remaining patients were lost to follow-up.
C. Rollino et al.
Markers of aVSMC phenotype
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14. Gupta K, Hooton TM, Naber KG et al. International clinical
practice guidelines for the treatment of acute uncomplicated cystitis
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Received for publication: 2.5.2011; Accepted in revised form:
30.12.2011
Nephrol Dial Transplant (2012) 27: 3493–3501
doi: 10.1093/ndt/gfr811
Advance Access publication 8 February 2012
Arteriolar vascular smooth muscle cell differentiation
in benign nephrosclerosis
Clemens Luitpold Bockmeyer1,*, David Sebastian Kern1, *, Vinzent Forstmeier1, Svjetlana Lovric2,
Friedrich Modde1, Putri Andina Agustian1, Sandra Steffens3, Ingvild Birschmann4, Jana Traeder1,
Maximilian Ernst Dämmrich1, Anke Schwarz2, Hans Heinrich Kreipe1, Verena Bröcker1 and Jan
Ulrich Becker1
1
Institute of Pathology, Hannover Medical School, Hannover, Germany, 2Department of Nephrology and Hypertension, Hannover
Medical School, Hannover, Germany, 3Clinic for Urology, Hannover Medical School, Hannover, Germany and 4Clinic for
Haematology, Haemostaseology and Oncology, Hannover Medical School, Hannover, Germany
Correspondence and offprint requests to: Jan Ulrich Becker; E-mail: [email protected]
*Both authors contributed equally to this work.
Abstract
Background. Benign nephrosclerosis (bN) is the most
prevalent form of hypertensive damage in kidney biopsies. It is defined by early hyalinosis and later fibrosis of
renal arterioles. Despite its high prevalence, very little is
known about the contribution of arteriolar vascular
smooth muscle cells (VSMCs) to bN. We examined classical and novel candidate markers of the normal contractile and the pro-fibrotic secretory phenotype of VSMCs in
arterioles in bN.
Methods. Sixty-three renal tissue specimens with bN and
eight control specimens were examined by immunohistochemistry for the contractile markers caldesmon, alpha-
smooth muscle actin (alpha-SMA), JunB, smoothelin and
the secretory marker S100A4 and by double stains for caldesmon or smoothelin with S100A4.
Results. Smoothelin immunostaining showed an inverse
correlation with hyalinosis and fibrosis scores, while
S100A4 correlated with fibrosis scores only. Neither caldesmon, alpha-SMA nor JunB correlated with hyalinosis or fibrosis scores. Cells in the arteriolar wall were exclusively
positive either for caldesmon/smoothelin or S100A4.
Conclusions. This is the first systematic analysis of VSMC
differentiation in bN. The results suggest that smoothelin is
the most sensitive marker for the contractile phenotype and
that S100A4 could be a novel marker for the secretory
© The Author 2012. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
For Permissions, please e-mail: [email protected]
Downloaded from http://ndt.oxfordjournals.org/ at University of Auckland on September 4, 2012
2. Efstathiou SF, Pefanis AV, Tsioulos DI et al. Acute pyelonephritis in
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MR imaging, and power Doppler US in an experimental pig model.
Radiology 2001; 218: 101–108.
6. Levey AS, Greene T, Kusek JW et al. A simplified equation to predict
glomerular filtration rate from serum creatinine. J Am Soc Nephrol
2000; 11: 155A.
7. Fraser IR, Birch D, Fairley KF et al. A prospective study of cortical
scarring in acute febrile pyelonephritis in adults: clinical and bacteriological characteristics. Clin Nephrol 1995; 43: 159–164.
8. Warren JW, Abrutyn E, Hebel JR et al. Guidelines for antimicrobial
treatment of uncomplicated acute bacterial cystitis and acute pyelonephritis in women. Infectious Diseases Society of America (IDSA).
Clin Infect Dis 1999; 29: 745–758.
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