3488
prospective study JPHC (Japan Public Health Center)-based Pro-
spective Study. J Clin Epidemiol 2009; 62: 667–673.
22. Lindberg HA, Berkson DM, Stamler J et al. Totally asymptomatic
myocardial infarction: an estimate of its incidence in the living
population. Arch Intern Med 1960; 106: 628–633.
23. McClellan W, Warnock DG, McClure L et al. Racial differences in
the prevalence of chronic kidney disease among participants in the
Reasons for Geographic and Racial Differences in Stroke
Nephrol Dial Transplant (2012) 27: 3488–3493
doi: 10.1093/ndt/gfr810
Advance Access publication 17 February 2012
Acute pyelonephritis in adults: a case series of 223 patients
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: cristiana.rollino@libero.it
Abstract
Background. Acute pyelonephritis (APN) is a common
disease which rarely evolves into abscesses.
Methods. We prospectively collected clinical, biochemi-
cal 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 differ-
ences were found between patients with positive or nega-
tive 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 pre-
vious antibiotic treatment, low bacterial growth or atypical
pathogens. Systematic CT or NMR is necessary to
exclude evolution into abscesses, which cannot be sus-
pected on clinical grounds or by ultrasound examination
and may also develop in the absence of risk factors.
© The Author 2012. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
For Permissions, please e-mail: journals.permissions@oup.com
C. Rollino et al.
(REGARDS) Cohort Study. J Am Soc Nephrol 2006; 17:
1710–1715.
24. Kottke TE, Daida H, Bailey KR et al. Reliability of the Minnesota
and Mayo electrocardiographic coding systems. J Electrocardiol
1998; 4: 303–312.
Received for publication: 31.3.2011; Accepted in revised form:
30.10.2011
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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
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 per-
formed 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 bac-
teria. When no response was observed after 72 h, treatment was modu-
lated 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
‘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.; leucocyto-
sis 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 hypo-
dense parenchymal areas were evidenced after contrast medium infusion.
In NMR, APN areas correspond to hypointense areas in T1 after ga-
dolinium 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.
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.
3489
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 evi-
denced by renal biopsy; this patient transiently required
dialysis.
Risk factors were present in 60 patients (26.9%)
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(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 cipro-
floxacin 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 invol-
vement (5 patients) and abscesses (2 patients) were
evidenced.
3490 C. Rollino et al.
Table 1. Characteristics of the patients CT scan was performed on 183/223 (82.06%) patients.
It was normal in 12 cases (6.5%); it showed lesions sug-
Patients (N) 223
Female/male 202/21
gestive for APN in 170/183 cases (92.8%), with evidence
Right/left kidney 1.5 of single or multiple areas of parenchymal hypodensity
Mean age (years) 37.77 ± 17.61 (Figure 2). Concordance between CT scan and ultrasound
Duration of symptoms before hospitalization (days) 5.79 ± 11.15 was 49%.
Mean ear temperature (°C) 39.18 ± 0.79 NMR was performed in 57 cases (47 positive and 10
Duration of fever (days) 5.34 ± 6.85
Leucocytosis (N of patients) 183 (82.06%) negative). Among the 170 patients with positive CT, 26
Mean leucocytes (/mm3) 16 960 ± 5869 were also evaluated with NMR, which resulted positive in
Mean CRP (mg/dL) 15.65 ± 8.56 21 and negative in 5. In one case, NMR showed an
Positive urine culture (N) 64/208 (30.7%) abscess which had not been documented by CT. Thirty
Positive blood culture (N) 39/182 (21.4%)
Both urine and blood positive culture (N) 19/171 (11.1%)
patients were submitted to NMR only: this examination
Pyuria (N) 147/223 (65.92%) documented APN in 25 patients.

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Risk factors (N of patients) 60/223 (26.9%) In total, 213 patients were submitted for CT and/or
Presence of renal failure 21/223 (9.4%) NMR (95.5%). A radiological confirmation of APN by
Days of hospitalization 11 ± 11 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,
Table 2. Characteristics of the patientsa urine or blood cultures were negative, but TC/NMR was
positive for APN. In the 12 patients with normal CT,
Diabetes 14 blood or urine cultures were positive.
Pregnancy 2 No differences were found between patients with posi-
Renal transplant 6 tive or negative CT or NMR with regard to body tempera-
Recent hospitalization (by 3 months) 11
Kidney stones 13 ture at admission, leucocytosis, CRP and duration of
Vesico-ureterale reflux 9 symptoms before hospitalization (Table 3). Urine and
Anatomical defects (ureteral duplication, ureteropyelic junction 5 blood cultures were positive more frequently in patients
stenosis, renal ectopia) with negative CT/NMR (Table 4).
Neurological bladder 3
New bladder after cystectomy 3
Fifty of the 213 patients submitted to CT/NMR
Prostatitis 2 (23.5%) had single or multiple intrarenal abscesses
Self-catheterization 2 (Figure 3). Ultrasound examination evidenced abscesses
Endocarditis 1 in only two patients. No differences were found between
Balanoposthitis 1 patients with or without abscesses with regards to body
Actinic cystitis 1
Permanent catheter 1 temperature, leucocytosis, duration of fever, duration of
symptoms before hospitalization, CRP pyuria and urine
a
Risk factors: number of patients. cultures (Table 5). Patients with abscesses were

Fig. 2. Spiral CT: multiple areas of APN in the left kidney.

APN in adults: a case series 3491
a
Table 3. Comparison between positive and negative CT/NMR patients

CT/NMR negative CT/NMR positive Significance

Leucocytes (/mm3) 18 290.59 ± 12 216.05 15 209.19 ± 5777.37 n.s. (P 0.06)

CRP (mg/dL) 12.22 ± 80.6 16.09 ± 8.63 n.s. (P 0.08)
Duration of symptoms before hospitalization (days) 10.63 ± 21.11 5.45 ± 10.10 n.s. (P 0.08)
Temperature (°C) 39.17 ± 0.94 39.21 ± 0.78 n.s. (P 0.85)
a
n.s., not significant.

Table 4. Comparison between positive and negative CT/NMR patients concerning urine and blood culturea

CT/NMR negative CT/NMR positive Significance, P

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Positive urine culture 10/17 (58.8%) 46/183 (25.1%) 0.0033
Positive blood culture 8/11 (72.7%) 30/165 (18.1%) 0.000001
Urine and blood positive culture 11/13 (84.6%) 59/192 (30.7%) 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

Abscess absence Abscess presence Significance

Positive urine culture 47/149 (31.5%) 10/50 (20%) n.s. (P 0.07)

Pyuria (presence) 102/153 (66.6%) 30/48 (62.5%) n.s. (P 0.59)
Leucocytosis (N/mm3) 14 979.67 ± 6434.85 16 912.72 ± 6676.36 n.s. (P 0.11)
CRP (mg/dL) 16.06 ± 8.48 14.87 ± 9.09 n.s. (P 0.4)
Temperature (°C) 39.16 ± 0.81 39.38 ± 0.66 n.s. (P 0.12)
Days of fever 5.44 ± 7.52 5.48 ± 4.23 n.s. (P 0.98)
Days of hospitalization 8.63 ± 9.67 16.68 ± 14.15 P 0.000008
Duration of symptoms before hospitalization (days) 6.23 ± 12.69 4.51 ± 4.16 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.
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 urethrocystogra-
phy was performed, VUR was found in 9 patients
(20.9%).
Outcome
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 re-
maining patients were lost to follow-up.
Contrast medium for CT induced a transient increase in
serum creatinine in the patients with renal failure; creati-
nine returned to previous values in all cases afterwards.
VUR. Among the patients with VUR, which was there-
after 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 un-
certain indications in the literature with regard to the op-
portunity 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 con-
firmed by either CT scan or NMR had positive urine
culture (Table 4) and that 23.5% of the 213 patients sub-
mitted to CT/NMR had single or multiple intrarenal ab-
scesses (Figure 3).
The low frequency of positive urine culture may be ex-
plained by previous antibiotic treatment, either self-pre-
scribed or prescribed by the general practitioner, and by
the possibility that infection was confined to the renal par-
enchyma. Moreover, atypical organisms, such as Urea-
plasma urealyticum (responsible for 4.8% of APN cases
[7]) and Mycoplasma hominis, which are not found
C. Rollino et al.
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 stan-
dard 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 examin-
ation or that they were so mild as to be undetectable.
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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 detec-
tion 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 cav-
ities 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 re-
lapsing 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 ci-
profloxacin 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 fluoroqui-
nolone, an aminoglycoside with or without ampicillin, an
extended spectrum cephalosporin with or without amino-
glycoside or a carbapenem). Much concern regards anti-
biotic 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 prac-
tice. Renal abscesses are frequent and may not be sus-
pected 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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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: JanBecker@gmx.com
*Both authors contributed equally to this work.

Abstract smooth muscle actin (alpha-SMA), JunB, smoothelin and

Background. Benign nephrosclerosis (bN) is the most
prevalent form of hypertensive damage in kidney biop-
sies. 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 clas-
sical and novel candidate markers of the normal contrac-
tile 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 immunohisto-
chemistry for the contractile markers caldesmon, alpha-
the secretory marker S100A4 and by double stains for cal-
desmon or smoothelin with S100A4.
Results. Smoothelin immunostaining showed an inverse
correlation with hyalinosis and fibrosis scores, while
S100A4 correlated with fibrosis scores only. Neither caldes-
mon, alpha-SMA nor JunB correlated with hyalinosis or fi-
brosis 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

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