|Year : 2021 | Volume
| Issue : 1 | Page : 243-247
Evaluation of oxidant–antioxidant balance and total antioxidant capacity in urinary tract infection in children
Fahima M Hassan1, Basim A El-Gazzar1, Mohamed G El-Helbawy2, Manar H Elhabashy3
1 Department of Pediatrics, Faculty of Medicine, Menoufia University, Shebin El-Kom, Menoufia, Egypt
2 Department of Clinical Pathology, Faculty of Medicine, Menoufia University, Shebin El-Kom, Menoufia, Egypt
3 Department of Pediatrics, Ministry of Health, Shebin El-Kom, Menoufia, Egypt
|Date of Submission||02-Sep-2019|
|Date of Decision||15-Oct-2019|
|Date of Acceptance||20-Oct-2019|
|Date of Web Publication||27-Mar-2021|
Manar H Elhabashy
Shebin El-kom, Menoufia
Source of Support: None, Conflict of Interest: None
The aim was to detect serum levels of oxidative stress (OS) biomarkers [malondialdehyde (MDA) and total antioxidant capacity (TAC)] in children suffering from urinary tract infection (UTI).
Reactive oxygen species (ROS) are normally produced in low levels during tissue metabolism and are necessary for several biological processes. However, higher levels of ROS might cause damage to cells. Cellular damage by ROS could be prevented by different types of either endogenous or exogenous antioxidant. UTI is the most common bacterial infection in children and a major cause of hospitalization resulting in bad affection of the pediatric kidney.
Patients and methods
This case–control study was conducted on 100 children (75 patients: 25 controls) from 3 to 15 years old. From 100 children, 59 were women while 41 were men. They were selected from the outpatient clinic of nephrology of Menoufia University Hospital and Outpatient Clinic of Shebin El-Kom Fever Hospital from January 2018 to January 2019. Oxidant–antioxidant balance biomarkers (MDA and TAC) were quantified in serum samples and urine culture was performed to identify the causative organism of UTI.
There was significant increase in serum MDA while a decrease in TAC in UT-infected children. Escherichia coli was the most responsible microorganism for UTI in children.
UTI in children badly affect their health causing an increase in MDA and a decrease in TAC serum levels resulting in decreasing the protecting effects of antioxidants on the body of children.
Keywords: malondialdehyde, total antioxidant capacity, urinary tract infection
|How to cite this article:|
Hassan FM, El-Gazzar BA, El-Helbawy MG, Elhabashy MH. Evaluation of oxidant–antioxidant balance and total antioxidant capacity in urinary tract infection in children. Menoufia Med J 2021;34:243-7
|How to cite this URL:|
Hassan FM, El-Gazzar BA, El-Helbawy MG, Elhabashy MH. Evaluation of oxidant–antioxidant balance and total antioxidant capacity in urinary tract infection in children. Menoufia Med J [serial online] 2021 [cited 2021 Oct 23];34:243-7. Available from: http://www.mmj.eg.net/text.asp?2021/34/1/243/312048
| Introduction|| |
Urinary tract infection (UTI) is a common and potentially severe infection that represents a major burden of health-care utilization/expenditure and antibiotic exposure in children . Diagnosis of UTI relies on suggestive symptoms, pyuria, and isolation of an uropathogen in the culture. However, UTI symptoms in children often are nonspecific, and culture results are not available at the time of initial evaluation. Consequently, providers frequently rely on rapid results of the urine dipstick to decide whether to initiate empiric antibiotic therapy for a presumed UTI while awaiting culture results .
Reactive oxygen species (ROS), including hydroxyl radicals, superoxide anions, and hydrogen peroxide, are normally produced in low levels during tissue metabolism. These low quantities of ROS are necessary for several biological processes, including apoptosis, immunity, and defense mechanism against microorganisms while high levels of ROS could be harmful to cells and can be defined as oxidative stress (OS), which might cause damage to the affected cells. This cellular damage could be prevented by different types of either endogenous or exogenous antioxidants . Malondialdehyde (MDA) is the main indicator for lipid peroxidation which could be increased in response to various types of diseases. UTI causes OS and leads to suppression of antioxidant enzymes. Kidney damage during a UTI is associated with inflammation and increased production of oxidative-free radicles in the blood .
The aim of this study was to determine the effects of UTI in children on the balance between oxidants and antioxidants by measuring serum levels of MDA and total antioxidant capacity (TAC).
| Patients and methods|| |
A case–control study was conducted on 100 children, 59 women and 41 men (3–15 years of age). They were selected from the outpatient clinic of nephrology of Menoufia University Hospital and outpatient clinic of Shebin El-Kom Fever Hospital from January 2018 to January 2019. All examinations and investigations involved in this study protocol were approved by the Local EthicsCommittee of the Menoufia University.
Children suffering from dysuria, abdominal pain, loin pain, tenderness, fever with or without rigors, lethargy and anorexia, vomiting or diarrhea, hematuria, offensive and/or cloudy urine, and enuresis were selected to be included in this study , whereas children refusing cooperation, receiving antibiotics during the week prior to examination, receiving anti-inflammatory drugs during 3 days prior to examination, underlying rheumatic or inflammatory disease, and those having urinary tract malformation were excluded from this study.
All patients and controls were subjected to written consent from parents, careful history taking as well as the following examination and investigations: (a) complete systemic examination (abdominal, chest, cardiac, and neurological), (b) anthropometric measurements (weight in kilograms–length in centimeters–, (c) complete blood count by fully automated blood cell counter (PCE210N, Erma Inc., Tokyo, Japan), (d) serum C-reactive protein was measured by latex serology test (qualitative method) by nephlometry using a specific protein analyzer (MISPA I2 machine; Agappe Diagnostics Ltd, Agappe Hills, Ernakulam, Kerala, India), (e) urine analysis: microscopic examination of urine samples and detection of pus cells suggest occurrence of UTI, (f) urine culture: bacterial culture was performed according to the standard method on a nutrient agar and then on selective media. Types of isolated bacteria were identified by biochemical tests. Culture of at least 50000 colony-forming units of a single uropathogen is considered positive according to Masika et al. , (g) MDA in serum (colorimetric method):thiobarbituric acid (TBA) reacts with MDA in acidic medium at a temperature of 95°C for 30 min to form TBA reactive product. The absorbance of the resultant pink product can be measured at 534 nm wavelength according to the manufacturer instruction of the company (Diagnostic and Research Reagents; Bio Diagnostic) El-Tahrer St. - Dokki- Giza - Egypt. MDA then could be calculated in nmol following the protocol outlined by Ohkawa et al.  and (h) TAC in the serum (colorimetric method): ROS are produced as a consequence of normal aerobic metabolism. Unstable free radical species attack cellular components causing damage to lipids, proteins, and the DNA, which can initiate a chain of events resulting in the onset of a variety of diseases. Living organisms have developed complex antioxidant systems to counteract ROS to reduce their damage. The determination of antioxidative capacity is performed by the reaction of antioxidants in the sample with a defined amount of exogenously provided hydrogen peroxide (H2O2); the antioxidants in the sample eliminate a certain amount of the provided H2O2. The residual H2O2 determined calorimetrically by an enzymatic reaction which evolves the conversion of 3, 5, dichloride-2-hydroxyl benzenesulfonate to a colored product. Calculation: total antioxidant concentration = mmol/l = A B–A SA × 3.33 .
Collected data were entered into the computer as numerical or categorical, as appropriate and analyzed using SPSS 18 (the Statistical Package for Social Sciences; SPSS Inc., Chicago, Illinois, USA) program. Two types of statistics were performed: (a) descriptive statistics (quantitative data were shown as mean ± SD, minimum and maximum and qualitative data were expressed as frequency and percent) and (b) analytical statistics (χ2-test and Fisher's exact test were used to measure the association between qualitative variables as appropriate and Mann–Whitney and independent sample t-tests were done to measure the association between two quantitative variables as appropriate. Probability value was considered to be of statistically significant if less than 0.05.
| Results|| |
Results of demographic data showed that patients included 42 female and 33 male cases with 8.97 ± 2.778 years of age, while controls were 17 women and 8 men of 8.20 ± 2.466 years of age. There was no significant difference between cases and controls as regards age, sex, and residence (P > 0.219, 0.291 and 0.291), respectively. Socioeconomic status significantly affected the occurrence of UTI in cases (P < 0.001) and was 13, 18, and 33 with high, moderate, and low level, respectively. For the control group, the 25 children were all of moderate level. Residence data showed that 42 cases out of 75 were from the urban area while 33 were from the rural area. The control group included 17 children from urban while eight were from rural area as presented in [Table 1].
Clinically, we found that positive cases of UTI were significantly presented by dysuria, chills, urgency, frequency, cloudy urine, and history of a similar condition (P < 0.001*) while it insignificantly correlated to hematuria (P > 0.185) as shown in [Table 2].
Hematological data showed that there was a significant difference between the case and the control group regarding hemoglobin (Hb) and total leukocytic count (TLC) (P < 0.016 and 0.031, respectively), while platelet values were insignificantly affected by UTI in cases (P > 0.086) compared with controls. Hematological data of the studied cases and controls is presented in [Table 3].
Urine culture of cases revealed a higher percentage for Escherichia coli, followed by Klebsiella spp. then Proteus spp. and finally with Enterococcus faecalis in a descending manner (46.66, 22.66, 16, and 14.66%, respectively) as presented in [Table 4].
Values of serum TAC and MDA showed that there was a highly significant difference (P < 0.0001* and 0.001*), respectively, between cases and controls. Results of serum TAC and MDA of the cases and control group are shown in [Table 5].
|Table 5: Total antioxidant capacity and malondialdehyde of the cases and control group|
Click here to view
| Discussion|| |
UTI is ranked the second important disease in children and adults following respiratory diseases. UTI is considered one of the most highly occurring bacterial infection affecting children with high incidence in girls (7%) than boys (2%) under the age of 6 years. Therefore, early and appropriate diagnosis is highly important in young children, otherwise complications of hypertension and/or renal failure might occur .
High levels of oxidants (i.e., ROS) and/or low levels of antioxidants could result in a state of imbalance between oxidants and antioxidants within the body causing OS. It is well known that OS plays a major role in the pathogenesis of various renal diseases such as UTI as well as potentiate the disease course. Antioxidants are highly important defense mechanism against OS- and free radical-induced renal damage. Therefore, monitoring the antioxidant capacity is valuable to improve the antioxidant status and hence health of children. Either endogenous or exogenous antioxidants are capable of neutralizing the free radicals protecting the health of children during ROS-induced oxidative damage .
Insignificant statistical differences between the case and control groups regarding age, sex, and residence were consistent with earlier reports by Lee et al. , AbdEl-Salam et al. , and Soleimani et al. , in children suffering from UTI. However, in the current study female cases recorded higher incidence of UTI (n = 42 cases; 56.0%) compared with male cases (n = 33 cases; 44.0%) was consistent with the results obtained by Soleimani et al. , who observed a higher incidence of UTI in women (74%) than men (26%). The significant effect of socioeconomic status in cases (P < 0.001) compared with controls was reflected on the occurrence of UTI in high (17.3%), low (58.7%), and moderate (24.0%) socioeconomic status, respectively. For the control group, the 25 children were all in the moderate level. Our data were consistent with those of Fahmy et al. .
In our study according to clinical presentation, the positive cases of UTI were significantly presented by dysuria, chills, urgency, frequency, cloudy urine, and history of a similar condition (P < 0.001*) while insignificantly correlated to bloody urine (P > 0.185) was highly consistent with previous reports of White , who found that UTI presented by abdominal pain or flank pain, dysuria, and frequency. Yousefichaijan et al.  outlined that UTI presentation may be occurred in the form of abdominal, back, or flank pain, nausea and vomiting and Stein et al.  observed that UTI may be presented by dysuria, urgency, and frequency. In contrast, our data of negative UTI during hematuria was inconsistent with Stein et al. , who found that the presentation of UTI may be in the nature of hematuria.
The significant difference between case and control groups of hematological data regarding Hb and TLC (P < 0.016 and 0.031, respectively), might be attributed to the majority of women within the control group that might result in decreased Hb level whilst for TLC, it might be explained by the inflammatory defense mechanism of the white blood cells against renal infection during UTI. Lee et al.  stated that WBCs were significantly higher in acute pyelonephritis than lower UTI in children (P = 0.001). Moreover, Xu et al.  observed a significant increase of WBCs in cases of pyelonephritis and lower UTI and Abd El-Salam et al.  reported that cases of UTI have a higher significant increase of TLC On the other hand, platelets values were insignificantly affected by UTI in cases (P > 0.086) compared with controls in agreement with Lee et al. , who found that the platelet count revealed insignificant difference (P = 0.742).
The higher percentage for E. coli, followed by Klebsiella spp. then Proteus spp. and finally with Enterococcus faecalis of urine culture in UTI cases of our study was mainly consistent with previous reports of White  and Soleimani et al. , who noticed that the most responsible bacterial pathogens causing UTI in children was E. coli (82%), followed by Klebsiella spp., Proteus spp., Enterobacter spp., Citrobacter spp., Staphylococci spp., and finally Enterococci spp. Silva and Olivera  reported that the major UTI-causing pathogen in children was E. coli, followed by Klebsiella spp., Enterococci spp., and finally Proteus spp. In this regard, Saeed et al.  found that E. coli represented the highest incidence (33.9%), then Proteus spp. (9.3%), then Klebsiella pneumonia (5.1%) and lastly Enterococci spp. (4.2%). Yang et al.  too reported that the main causative agents responsible for UTI in children were as follows: E. coli (n = 292), followed by Klebsiella pneumoniae (n = 31), Proteus mirabilis (n = 29), Streptococci spp. (n = 23), Enterococci spp. (n = 9), and finally Citrobacter spp. (n = 5). Moreover, Masika et al.  investigated 31 positive UTI samples for bacterial growth from which 64.5% of the growing organisms was E. coli., followed by E. faecalis and Klebsiella spp.
The high significant difference between case and control groups for TAC and MDA values (P < 0.001* and 0.001*), respectively, were represented by the lower serum level of TAC while the higher serum level of MDA in cases compared with controls might be attributed to UTI-induced OS in children. Our data were consistent with earlier reports of Kurutas et al. , who found a four-time increase in levels of MDA in positive urine cultures compared with negative urine cultures which in turn resulted in lower levels of TAC and enzymes involved in antioxidants such as catalase (CAT) and superoxide dismutase (SOD) in patients suffering from UTI. Previous report by Delshad et al. , who evaluated the OS biomarkers in children ranging from 3 weeks to less than 17 years with UTI revealed that there were increased MDA levels while decreased TAC levels compared with the control group. In this regard, Soleimani et al.  studied TAC in the serum of children suffering from UTI and found imbalance between oxidant and antioxidant status during the course of UTI with a disturbed ratio of oxidative stress index (OSI) compared with the control group. For antioxidant status, Abd El-Salam et al.  and Ciftci et al.  studied the relation between UTI and levels of both TAC and vitamin C as an indicator for antioxidant level and found a significant decline in levels of both TAC and vitamin C in cases compared with control. Moreover, Petrovic et al.  investigated 50 Caucasian children (median age was 6 months) suffering from UTI and found a significant higher total antioxidant status during longer duration compared with shorter duration of inflammation and the total antioxidant status OS markers during UTI are sensitive to accompanying the inflammatory condition.
| Conclusion|| |
UTI represents a stressful condition causing OS on the health of children, decreasing their antioxidant protective mechanisms resulting in decreased TAC, while increasing MDA serum levels during the course of UTI in children. Urine culture results revealed that E. coli was the most responsible organism for UTI in children.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Spencer JD, Schwaderer A, McHugh K, Hains DS. Pediatric urinary tract infections: an analysis of hospitalizations, charges, and costs in the USA. Pediatr Nephrol 2010; 25
Watson JR, Hains DS, Cohen DM, Spencer JD, Kline JM, Yin H, et al
. Evaluation of novel urinary tract infection biomarkers in children. Pediatr Res 2016; 79
Kurutas EB, Cirgil P, Gul M, Kilinc M. The effects of oxidative stress in urinary tract infection. Mediators Inflamm 2005; 4
Petrovic S, Bogavac-Stanojevic N, Kotur-Stevuljevic J, Peco-Antic A, Ivanisevic I, Ivanisevic J, et al.
Oxidative status parameters in children with urinary tract infection. Biochemiamedica 2014; 24
Lissauer T, Clayden G. Illustrated Textbook of Paediatrics
ed. Edinburgh London New York Oxford Philadelphia St Louis Sydney Toronto: Mosby Elsevier 2012 Elsevier Ltd; 2012. p325.
Masika WG, O'Meara WP, Holland TL, Armstrong J. Contribution of urinary tract infection to the burden of febrile illnesses in young children in rural Kenya. PLoS One 2017; 12
Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979; 95
Koracevic D, Koracevic G, Djordjevic V, Andrejevic S, Cosic V. Method for the measurement of antioxidant activity in human fluid. J Clin Pathol 2001; 54
Soleimani G, Sadeghi-Bojd S, Teimouri A, Nakhaee A, Sheikhhosseini A. Evaluation of oxidant-antioxidant balance and total antioxidant capacity of serum in children with urinary tract infection. Niger Med J 2016; 57
Ozbek E. Review article induction of oxidative stress in kidney. Int J Nephrol 2012; 46
Lee IR, Shin J, Park SJ, Oh JY, Kim JH. Mean platelet volume in young children with urinary tract infection. Sci Rep 2015; 5
Abd El-Salam M, Ibrahim GE, Shiha AE. Evaluation of antioxidant capacity and ascorbic acid in children with urinary tract infection. IOSR J Pharm 2016; 6
Fahmy SI, Nofal LM, Shehata SF, El Kady HM, Ibrahim HK. Updating indicators for scaling the socioeconomic level of Families for health research. J Egypt Pub Health 2015; 90
White B. Diagnosis and treatment of urinary tract infections in children. Am Fam Physician 2011; 83
Yousefichaijan P, Kahbazi M, Rasti S, Rafeie M, Sharafkhah M. Vitamin E as adjuvant treatment for urinary tract infection in girls with acute pyelonephritis. Iran J Kidney Dis 2015; 9
Stein R, Dogan HS, Hoebeke P, Kŏcvara R, Nijman RJ, Radmayr C, et al
. Urinary tract infections in children: European Association of Urology; European Society for Pediatric Urology (EAU/ESPU) guidelines. Eur Urol 2015; 67
Xu RY, Liu HW, Liu JL, Dong JH. Procalcitonin and C-reactive protein in urinary tract infection diagnosis. BMC Urol 2014; 14
Silva AC, Oliveira EA. Update on the approach of urinary tract infection in childhood. Jornal de Pediatria (VersãoemPortuguês) 2015; 91
Saeed CH, Al-Otraqchi KI, Mansoor IY. Prevalence of urinary tract infections and antibiotics susceptibility pattern among infants and young children in Erbil city. Zanco J Med Sci 2015; 19
Yang CC, Chang SJ, Yang SS, Lin CD, Peng CH. Rapid diagnosis of uncomplicated urinary tract infection with laser flow cytometry. Urol Sci 2016; 27
Delshad M, Fesharakinia A, Eghbal S. The role of oxidative stress in pediatric urinary tract infections: a systematic review. Rev Clin Med 2016; 3
Ciftci H, Verit A, Yeni E, Savas M. Decreased oxidative stress index of urine in patients with urinary tract infection. Urol Int 2008; 81
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]