Accepted Manuscript Association between urinary tract infection and urinary tract abnormalities: a casecontrol study in Erbil City N.E. AlKhateeb , MSc S. Al Azzawi , FRCPCH N.G. Al Tawil PII:
S1477-5131(14)00158-2
DOI:
10.1016/j.jpurol.2014.05.006
Reference:
JPUROL 1714
To appear in:
Journal of Pediatric Urology
Received Date: 13 February 2014 Accepted Date: 22 May 2014
Please cite this article as: AlKhateeb NE, Al Azzawi S, Al Tawil NG, Association between urinary tract infection and urinary tract abnormalities: a case-control study in Erbil City, Journal of Pediatric Urology (2014), doi: 10.1016/j.jpurol.2014.05.006. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Association between urinary tract infection and urinary tract abnormalities: a case-control study in Erbil City
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Authors: N.E. AlKhateeb MSca, S. Al Azzawi FRCPCHa, N.G. Al Tawilb
Affiliations: a
Pediatric Department, College of Medicine, Hawler Medical University, Erbil, Iraq
b
Emails:
[email protected] [email protected] Corresponding author:
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[email protected] Nazdar E. AlKhateeb MSc Pediatric Senior Lecturer
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Pediatric Department College of Medicine
Iraq
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Hawler Medical University Erbil
PO 178
009647504534461
[email protected] M AN U
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Department of Community Medicine, College of Medicine, Hawler Medical University. Erbil, Iraq
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Summary Objective: To determine the proportion of ultrasound abnormalities of the
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urinary system between two groups of children: affected with urinary tract infection (UTI) and unaffected (control). Further, to determine the most
common microorganisms causing UTI in those children with urinary tract
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abnormalities.
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Methods: A case-control study was carried out in Erbil, Iraq between September and December 2012. Ultrasound examinations were carried out on 64 children affected with UTI and on 64 unaffected with UTI (control) in order to detect differences, in the presence of abnormalities, in the urinary tract
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between the two groups.
Results: A majority (59.4%) of children affected with UTI had ultrasound
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abnormalities, compared with 26.6% of the control group (P < 0.001).
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Escherichia coli was the most common microorganism in both groups, although the difference was not statistically significant. More than one half (75%) of patients with UTI were female, compared with 25% who were male (P < 0.001).
Conclusion: More than one half of the children in the present study who presented with UTI were found to have ultrasound abnormalities. Escherichia
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coli was the most common causative pathogen for children with or without ultrasound abnormalities.
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Key words:
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Introduction UTI is a problem that is frequently encountered by pediatric healthcare
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providers worldwide. Over recent decades, the importance of UTI has been increasingly recognized, in particular, the role of UTI as an occult cause of febrile illness in young children. [1] Normal anatomy and physiology of the
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urinary tract with unidirectional urinary flow and complete emptying at regular,
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reasonable intervals should protect children from UTIs. [2]
Urinary tract infection (UTI) is one of the most common bacterial infections of childhood, with the incidence ranging between 1-1.5% in boys and 3-8% in girls [3,4]. In the first year of life, UTI is more prevalent in boys, with a rate of
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2.7% compared with 0.7% in girls. Studies have shown a 10 to 12 fold increased risk of UTI in uncircumcised boys. [4]
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The diagnosis of UTI in young children is important, as it is a marker for
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urinary tract abnormalities. Imaging studies to detect congenital or acquired abnormalities are recommended following the first UTI in all children under six years of age. [5] Morbidity of UTI is not limited to acute periods of illness. It may also result in renal scarring, which has the potential for diminished renal function and hypertension. [2]
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Few studies in developing countries have assessed the prevalence of urinary tract abnormalities in children. [4] The aim of the present study was to find out
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the proportion of ultrasound abnormalities of the urinary system in a group of children less than 12 years of age who were affected with UTI, in Erbil, Iraq, and to compare this with the proportion of the ultrasound abnormalities among
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children unaffected with UTI. Further, to find out the most common
Patients and Methods
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microorganisms causing UTI in those patients with urinary tract abnormalities.
A case-control study was performed in a private clinic in Erbil, ‘the capital of
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the Iraqi Kurdistan region’, between September and December 2012. Inclusion criteria were all children less than 12 years of age, febrile or afebrile,
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with first proven UTI provided that there was no evident cause of fever.
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Exclusion criteria were children on current antibiotic therapy. A comparison group of the same-aged children and the same sample size was collected in the same clinic; this group consisted of children attending the clinic for reasons unrelated to urinary tract problems or abnormalities. The convenience method of sampling was used to collect the comparison group.
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A questionnaire was designed by the researchers and included: age, gender, presenting symptoms, presence of abdominal pain, any urinary symptoms,
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any abnormal odor noticed by the caregiver, and history of circumcision. The questionnaire also included results of the physical examination, like:
abdominal examination, any evident congenital abnormalities, abnormal
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feces, presence of hernia, undescended testis, and hypospadias.
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The specimen of urine was collected by the standard method of midstream urine sample, or by application of a sterile urine bag after washing the perineal area. More than two or three white blood cell/high power field with 100 objectives or the presence of red blood cells was considered to be abnormal
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and sent for urine culture and sensitivity. A positive result was defined as the growth of a single urinary tract pathogen at 105 colony forming unit/ml. [6]
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Those who had a mixed-growth culture were repeated. In addition to the general urine examination (GUE) and culture, in febrile children, blood
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samples were collected for complete blood picture (CBP). All children underwent a thorough ultrasound examination. Ethical approval was obtained from the Research Ethics Committee at Hawler Medical University. Oral consent was taken from the parents of each child enrolled in the study.
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Statistical analysis Data were analyzed using the Statistical package for Social Sciences (SPSS
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version 21). The Chi-squared test of association was used to compare
between proportions. When the expected count of more than 20% of the cells
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≤ 0.05 was considered to be significant.
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of the table was less than 5, the Fischer Exact test was used. A P-value of
Results
A total of 128 children were enrolled in the present study: 64 children who
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presented with UTI were considered to be the patient group, and another 64 children having no UTI (urine culture negative) were the control group. Their
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ages ranged from one-month to 12 years; the mean age (+SD) was 37.14 ±
group.
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34.7 months for the patient group, and 41.83 ± 33.7 months for the control
Table 1 shows that there were no significant differences in the age distribution of the two study groups (P = 0.907). Significant differences were detected in the gender distribution, where 75% of the patient group was female compared with 25% of the control group (P < 0.001). All of the children underwent renal
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and bladder ultrasound examination; 43% had abnormal ultrasound results. The patient group had 59.4%, whereas the control group had 26.6% (P
0.05), except for Klebsiella, which was present in children with ultrasound abnormalities (P-value 0.03) (Table 4). E. coli was the most common pathogen among all children (with and without abnormalities), Proteus was the second, while Klebsiella and Staphylococcus were the third most common pathogens in children with abnormalities.
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Discussion UTI may be a presentation of a variety of underlying urinary tract
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abnormalities. [7] The value of performing ultrasound in children with UTI has been questioned in several reports, since the results do not affect the
management. Although RBUS is a poor screening test for genitourinary
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abnormalities among young children who have a history of UTI, [8] renal
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ultrasound remains necessary in evaluating infants after febrile UTI. Ultrasound has the advantage of being easily available, non-invasive and radiation free; considering these aspects, an ultrasound-based imaging protocol is attractive. [9] It is effective for early detection of renal and urinary
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tract anomalies, therefore ultrasound screening in early infancy may enable early treatment that can prevent renal dysfunction. [10]
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Several studies have shown that radiological abnormalities exist in as many
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as 25-55% of children investigated after their first UTI. [7] In the present study, 43% of total cases had abnormal ultrasound findings; the percentage of abnormal ultrasound was 59.4% among the patient group and 26.6% among the control group. These results were consistent with what was found in other studies done in Thailand (46%), [11] Sweden (41%), [9] Boston (43.9%), [12] Detroit (40.8%), [13] Texas (34%), [14] and Babil (30.3%). [6] They were,
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however, much higher than those found in Taiwan (28.7%), [15] and Lublin, [16] where only 3.5% of the studied patients in a ‘pediatric outpatient clinic’
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and 20.7% of children with UTI had abnormalities. This discrepancy might be attributed to the fact that in some areas of the world, renal ultrasound is done routinely in utero to detect fetal renal abnormalities, and these authors advise
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selective use of ultrasound, [6] or it might be due to the fact that the sample in
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the Taiwan study included only those who were less than five years old. [15] Approximately 10% of children are born with congenital abnormalities of the urinary tract, [14] but the present study’s results showed a much higher rate (26.6%) in the control group. This could be justified by exposure to water
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chlorination byproducts, which are significantly associated with urinary tract defects; [17] the amount of sulfate, chloride, nitrate and phosphate exceeded
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the maximum allowed concentration in most of the wells studied in Erbil. [18]
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The comprehensive epidemiology of UTI has been well described. The overall incidence of UTI in the pre-pubertal pediatric population is 3% in girls and 1% in boys. [19] This agrees with what was found in the present study, where female gender had a significant association with the development of UTI (OR = 7.6 (95% CI: 3.371-17.507)).
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Renal and bladder ultrasound is performed to rule out anatomic abnormalities of urinary tracts. [20] In the present study, bladder abnormality was the most-
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common abnormality (39.1%) seen in the patient group, followed by hydronephrosis (9.4%). It is worthwhile to note that the presence of crystal was the most common abnormal ultrasound finding in the control group
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(7.8%), this might be attributed to less water consumption or hard water
characteristics of Erbil water. [18] However, some of these children might
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develop a UTI in near future, as struvite is formed as a result of metabolic activity of urease-positive bacteria. [21]
There is little dispute that E. coli is the most common pathogen found in
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children. In addition to its prevalence in the present study, other studies have also shown E. coli to be the most common infective organism. [6,14,22,23] In
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the present study, E. coli was the most common pathogen among children with or without ultrasound abnormalities (Table 4). The second most common
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microorganism detected frequently from urine culture was Proteus, which is the same result as obtained in Babil. [6] Conclusion
More than half of the children presenting with urinary tract infections were found to have ultrasound abnormalities.
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E. coli remains the most common causative pathogen for patients with or
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without ultrasound abnormalities.
Recommendations
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Patients with UTI need a complete imaging work up. Other modalities of renal
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imaging should be available in Erbil; especially DMSA scans of the kidney. The high percentage of urinary tract abnormalities in this study and their relation to the environmental factors should be addressed further in new
Limitations of study
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prospective studies.
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All ultrasound studies were reviewed by a group of radiologists. However,
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inter-rater reliability was not assessed in this study. Lack of other facilities (VCUG and DMSA), bearing in mind that renal scars and VUR cannot be detected by ultrasound, although renal ultrasound findings are neither sensitive nor specific for VUR in children [20].
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Acknowledgements The authors thank Dr Hadiya Mahdi for her great effort and help in collecting
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the control cases.
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Conflict of interest
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None of the authors have any conflict of interest, financial or otherwise, to disclose. Funding
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None declared.
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References [1] Zorc J, Kiddoo DA, Shaw KN. Diagnosis and Management of Pediatric
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[6] Mehdi SS. The role of renal ultrasound in urinary tract infection in children. Medical Journal of Babylon 2004;1(3 and 4):333-40. [7] Ahmadzadeh A, Aksarpour S. Association of urinary tract abnormalities in children with first urinary tract infection. Pak J Med Sci 2007; 23(1): 88-91.
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[8] Nelson CP, Johnson EX, Logvinenko T, Chow JS. Ultrasound as a screening test for genitourinary anomalies in children with UTI. Pediatrics 2014;133(3):e 394-403.
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[9] Preda I, Jodal U, Sixt R, Stokland E, Hansson S. Value of ultrasound in evaluation of infants with first urinary tract infection. J Urol 2010;183:1984-8.
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impact of 2011 AAP guidelines on the diagnosis of vesicoureteral reflux using a historical series. J.Pediatr Urol 2014;10(1):182-5. [14] Balat A, Hill LL. Genitourinary abnormalities in children with urinary tract infections. Turk J Med Sci 1999; 29:59-63. [15] Haung HP, Lai YC, Tsai IJ, Chen SY, Tsau YK. Renal ultrasonography should be done routinely in children with first urinary tract infections. Urology 2008; 71(3):439-43.
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[16] Kobylińska-Babiej J, Dyduch A. Urinary system abnormalities in children of the pediatric outpatient clinics in Lublin. Wiad Lek 2003; 56(1-2):10-3. [17] Hwang BF, Magnus P, JK. Risk of Specific Birth Defects in Relation to
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Chlorination and the Amount of Natural Organic Matter in the Water Supply.
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[19] Curtis J, Clark, Wiliam A. KennedyII, Linda D, Shortliffe. Urinary tract infection in children: When to worry. Urol Clin N Am 2010; 37:229-41. [20] Mahant S, Friedman J, MacArthur C. Renal ultrasound findings and vesicoureteral refluxing children hospitalized with urinary tract infection. Arch
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Table1. Comparison between patient group and control group regarding age, gender and ultrasound abnormality
No.
UTI %
Total
No.
%
No.
%
73
57
73.4
26
40.6
Abnormal 17
26.6
38
59.4
Gender
55
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47
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Ultrasound abnormality Normal
P-value
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No UTI
43
48
75
16
25
64
50
Female
16
25
48
75
64
50
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Male
Age (months) 19
29.7
20
31.3
39
30.5
12-60
31
48.4
32
50
63
49.2
> 60
14
12
18.8
26
20.3
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< 12
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21.9
< 0.001
< 0.001
0.907
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Table 2. SPSS output of binary logistic regression analysis between UTI, as a dependent variable with female gender, and ultrasound abnormality,
Variables
B
P
OR
95% C.I. for OR
< 0.001 7.682
3.371
Ultrasound
0.009
3.053
1.324
-1.492 0.000
0.225
abnormality
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Constant
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Female gender 2.039
Upper
17.507
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Lower
1.116
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as an independent variable
7.043
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Table 3. Ultrasound abnormalities detected among the two study groups
1
Bladder abnormalities
Patient with
Control group P-value
UTI group N =
N = 64.
64. No. (%)
No. (%)
25 (39.1)
4 (6.3)
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ULS abnormality type
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‘thickened bladder wall’ Crystal
2 (3.1)
3
Hydronephrosis
6 (9.4)
2 (3.1)
0.27*
4
Hydroureter
2 (3.1)
0 (0)
0.49*
5
Single kidney
2 (3.1)
1 (1.6)
1.00*
6
Pelvic kidney
1 (1.6)
1 (1.6)
1.00*
7
Dilated pelvi-caliceal
1 (1.6)
1.00*
0 (0)
0.496*
1 (1.6)
2 (3.1)
1.00*
2 (3.1)
0 (0)
0.496*
1(1.6)
0(0)
1.00*
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Splitting of pelvi-caliceal 2 (3.1)
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system 9
1 (1.6)
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8
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2
system
5 (7.8)
< 0.001
Increased echogenicity
10 Loss of cortico-
0.44*
medullary differentiation 11 Renal cyst
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12 Urolithiasis
1 (1.6)
4 (6.3)
0.365*
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*Fisher’s exact test had been performed
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Table 4. Types of microorganisms by ultrasound findings Abnormal ULS
Normal ULS
microorganism
No. (%)
No. (%)
E. coli
17 (38.63)
14 (51.8)
Proteus
10 (22.72)
7 (25.9)
Klebsiella
6 (13.6)
0 (0)
Staphylococcus
6 (13.6)
3 (11.11)
Pseudomonas
2 (4.5)
Coliform
2 (4.5)
Enterobacter
1 (2.27)
Total
44 (100)
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0.68
0.88
0.033* 0.72*
0 (0)
0.503*
3 (11.11)
0.64*
0 (0)
1*
27 (100)
*Fisher’s exact test had been performed Note: Nine patients had more than one microorganism.
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P-value
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Type of