ArticleLiterature Review

Risk of Renal Scarring in Children With a First Urinary Tract Infection: A Systematic Review

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Abstract

To our knowledge, the risk of renal scarring in children with a urinary tract infection (UTI) has not been systematically studied. To review the prevalence of acute and chronic renal imaging abnormalities in children after an initial UTI. We searched Medline and Embase for English-, French-, and Spanish-language articles using the following terms: "Technetium (99m)Tc dimercaptosuccinic acid (DMSA)," "DMSA," "dimercaptosuccinic," "scintigra*," "pyelonephritis," and "urinary tract infection." We included articles if they reported data on the prevalence of abnormalities on acute-phase (≤15 days) or follow-up (>5 months) DMSA renal scans in children aged 0 to 18 years after an initial UTI. Two evaluators independently reviewed data from each article. Of 1533 articles found by the search strategy, 325 full-text articles were reviewed; 33 studies met all inclusion criteria. Among children with an initial episode of UTI, 57% (95% confidence interval [CI]: 50-64) had changes consistent with acute pyelonephritis on the acute-phase DMSA renal scan and 15% (95% CI: 11-18) had evidence of renal scarring on the follow-up DMSA scan. Children with vesicoureteral reflux (VUR) were significantly more likely to develop pyelonephritis (relative risk [RR]: 1.5 [95% CI: 1.1-1.9]) and renal scarring (RR: 2.6 [95% CI: 1.7-3.9]) compared with children with no VUR. Children with VUR grades III or higher were more likely to develop scarring than children with lower grades of VUR (RR: 2.1 [95% CI: 1.4-3.2]). The pooled prevalence values provided from this study provide a basis for an evidence-based approach to the management of children with this frequently occurring condition.

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... it is recommended to exclude vur in high-risk patients, i.e. those with hydronephrosis, kidney scarring, atypical uti, in children with complex conditions (urogenital anomalies, neurogenic bladder, or bowel dysfunction), and those with a positive family history of vur 3,4 . during childhood, about 8% of girls and 2% of boys have a uti, and it is estimated that there is underlying vur in 18%-40% of them 5,6 . it is recommended to exclude vur in the first febrile uti in a child from 2 months to 2 years of age in cases of atypical bacteria isolated from urine culture (all except for Escherichia (E.) coli) and pathologic findings of kidney and urinary tract ultrasound [6][7][8][9] . ...
... during childhood, about 8% of girls and 2% of boys have a uti, and it is estimated that there is underlying vur in 18%-40% of them 5,6 . it is recommended to exclude vur in the first febrile uti in a child from 2 months to 2 years of age in cases of atypical bacteria isolated from urine culture (all except for Escherichia (E.) coli) and pathologic findings of kidney and urinary tract ultrasound [6][7][8][9] . Kidney ultrasound has been shown to have neither specificity nor sensitivity for vur detection 10 . ...
... Furthermore, this diagnostic procedure should Pathologic urinary ultrasound findings normal urinary ultrasound findings not be performed during acute infection but after the infection has been treated 1,3,11 . determining vur grade in cevuS is similar to determining grades in voiding cystourethrography according to the 1985 international system of radiographic grading of vesicoureteric reflux (based on ureteral dilatation and renal duct system). in cevuS, grading is based on the presence of microbubbles of the ultrasound contrast agent in the ureter and renal duct system, as well as on the grades of dilatation, as follows: grade i -reflux into the distal part of the undilated ureter; grade ii -reflux reaches the proximal part of the drainage system without dilatation; grade iii -reflux into the dilated ureter and calyces with minimally blunted fornices; grade iv -reflux to the heavily dilated ureter; and grade v -severe reflux to the gross ureteral dilatation and tortuosity with a loss of papillary impressions 6,17,18 ...
Article
Vesicoureteral reflux (VUR) is one of the most common anomalies of the urinary system in children. Contrast-enhanced voiding urosonography (ceVUS) is one of the best methods in VUR diagnosis. This study compared characteristics associated with VUR specific images and categorized patients according to a particular VUR grade. The study included 183 children. VUR was detected in 38.9% of patients, mean age 1.7±1.1 years. Grade II VUR was most common (60.3%), followed by grade III (29.4%). Study results showed that VUR occurred irrespective of age, gender, previous ultrasound findings, causative agent, and severity of urinary tract infection (UTI). VUR was more common in children with recurrent UTI. In the group of children with the first UTI not caused by Escherichia coli or with recurrent UTI, boys more commonly suffered from severe VUR (grade IV-V; 66.7%), while girls suffered from moderate VUR (grade II-III; 100%). In this study, the incidence of VUR in prenatally diagnosed hydronephrosis was 28.6%. It is necessary to develop an algorithm for the treatment of children after UTI in Croatia, which should include ceVUS. All children with possible VUR should be referred to a specialized center where it is possible to perform ceVUS.
... If left untreated, the disease will progress and ascend to renal parenchyma, ending up with an acute pyelonephritis (APN). APN is a much more severe bacterial infection with the consequence of permanent kidney damage in infants (2,3). Besides, APN needs a longer antibiotic therapy than lower urinary tract infection does (4). ...
... Currently, two image strategies, renal ultrasonography and dimercaptosuccinic acid (DMSA) scintigraphy, are utilized to diagnose APN. DMSA scan particularly is the gold standard tool for the evaluation of renal parenchymal defects and permanent renal scarring (3,5). Nonetheless, due to risks of sedation and radiation exposure, some parents hesitate to accept this modality, not to mention taking in account the feasibility of this expensive equipment in some regional hospitals (6)(7)(8). ...
... DMSA scans are the gold standard tool for evaluation of renal parenchymal defects and permanent renal scarring (3,5). With DMSA alone it is difficult to differentiate renal scar from APN and renal scar might be the sequel of previous APN, instead of ongoing inflammatory process. ...
Article
Full-text available
Background: Detecting early predictors of acute pyelonephritis (APN) is essential for the prognosis, but few studies have focused on young infants specifically. Objectives: The aim of our research was to determine the relationship between APN and laboratory parameters in the age group less than 4 months. Methods: This retrospective study included patients aged less than 4 months with first time febrile urinary tract infection (UTI) between January 2012 and December 2018. White blood cells (WBC), C-reactive protein (CRP), and blood neutrophil/lymphocyte ratio (NLR) were analyzed. Patients were divided into two groups according to the presence of renal defects on dimercaptosuccinic acid (DMSA) scans. Results: In total, 205 patients were screened; 107 patients were in the APN group, and 98 patients were in the non-APN group. Compared with the non-APN group, the APN group showed significant differences in therapeutic response time (TRT), CRP, and NLR (all P values < 0.001). Multiple logistic regression analysis revealed that CRP, NLR, and TRT were independent risk factors for APN (P ≤ 0.001, 0.003, and 0.004, respectively). The area under the receiver operating characteristic (ROC) curve was 0.774 for CRP (P < 0.001). The optimum cut-off value for CRP was 4.27 mg/dL, with the highest sensitivity and specificity (70.1% and 73.5%, respectively). Conclusions: In the age group less than 4 months, without the image diagnosis, we could treat the patients as APN for longer antibiotic duration if CRP ≥ 4.27 mg/dL.
... The risk of renal impairment is greater in infants, and the diagnosis may be challenging to clinicians. The signs and symptoms of a UTI are often nonspecific, and the definitive diagnosis requires testing of a non contaminated urine sample collected by catheterization or suprapubic aspiration [10,11]. An accurate diagnosis is *Correspondence Dr. Debdutta Haldar Demonstrator, Dept. of Community Medicine, Diamond Harbour Government Medical College and south 24 Pgs District Hospital, West Bengal,, India. ...
... An accurate diagnosis is *Correspondence Dr. Debdutta Haldar Demonstrator, Dept. of Community Medicine, Diamond Harbour Government Medical College and south 24 Pgs District Hospital, West Bengal,, India. E-mail: debduttahaldar@gmail.com important to identify, evaluate and treat children at risk of UTI and renal scarring and to avoid over diagnosis and overtreatment in children who are not at risk [11,12]. Nevertheless, there are still differences between clinical guidelines on how to identify infants with FWS in whom UTI has to be ruled out in the paediatric emergency department (PED) [1,2,[13][14][15][16][17][18]. ...
Article
Full-text available
Background: Urinary tract infection (UTI) is one of the most common bacterial infections in infancy, with a high risk of recurrence, and maybe an indicator of underlying urinary tract abnormality. It is often misdiagnosed due to irregular and unrelated symptomatology in the absence of directed screening. Knowledge of baseline risk of urinary tract infection can help clinicians make informed diagnostic and therapeutic decisions. Objectives: The objectives of the study were to know the prevalence of UTI in infants with unexplained acute fever and to know other features of UTI besides fever. Methods: This was an observational, descriptive, cross sectional study. The study was conducted in private tertiary care hospital in Kolkata involving 110 infants attending the outpatient department of Paediatrics, KPC Medical College and Hospital from January 2020, to June 2020. Urine specimens were collected using midstream clean-catch urine (CCU) method and tested by urinalysis and culture. Template was generated in MS excel sheet and analysis was done on SPSS software. Results: Urine sample was successfully obtained from 110 infants, of which 66 (60%) were males, 44 (40%) were females. UTI was maximum present in age group 61-365 days (12.73%). In gender maximum UTI was present in males (11.82%). Majority of cases present with the temperature 38.30C to 38.90C (37.27%). Fever (100%) and Failure to thrive (70.91%) were the commonest presentation of cases selected for the study. Gastroenteritis was the most common illness observed in 33 (30%) infants. Conclusions: Prevalence rates of UTI varied by age, gender, race, and circumcision status. Prevalence estimates can help clinicians make informed decisions regarding diagnostic testing in children presenting with signs and symptoms of urinary tract infection.
... [27][28][29] Ten percent of white febrile infants and toddlers will have a UTI, whereas 2% of similar black children will have so in the absence of another source of infection. [2] Additional factors those predispose children to higher risk of developing UTI are high grade vesico-ureteric reflux (VUR), CAKUT, bowel bladder dysfunction (BBD), instrumentation of the urinary tract (particularly indwelling bladder catheterization), kidney stone, sextual activity, diabetes, genetic factors, etc. [22,26,[30][31][32][33] Antibiotic therapy may change periurethral flora that may also predispose to UTI. [34] Risk factors for renal scarring due to acute PN (APN) include high-grade VUR (mostly grades 4 and 5), [35,36] fever for more than 3 days before the initiation of antibiotics, [37][38][39] recurrent UTIs, [36,[40][41][42] and organism other than Escherichia coli. [43][44][45] A genetic predisposition has been found to be associated with recurrent UTI and renal scarring. ...
... It should be recommended during acute illness if the patient is not responding to treatment (beyond 48-72 h) to diagnose complications such as renal abscess, occult obstruction, stone etc. [11,41,91] •VCUG It is not routinely recommended after first febrile UTI as less than one-third of children with their first UTI have VUR and <10% of them have high-grade VUR (grades 4 and 5). [35,112] It should be considered after first UTI in children if abnormality is found in renal bladder US, UTI caused by atypical pathogen, complicated clinical course, known renal scarring. [41,[113][114][115] For those who have positive family history of VUR or CAKUT after first febrile UTI, VCUG should be also considered for them. ...
... Urinary tract infections (UTIs) are a common and significant clinical problem in both pregnant women and children. Infections that involve the upper urinary tract in children can result in renal scarring, hypertension, and end-stage renal disease (Shaikh et al., 2010;Salo et al., 2011). Similarly, outcomes in pregnant women can be affected by UTIs. ...
... In the meta-analysis conducted by Shaikh et al., it was found that circumcised boys have a two to four-fold decreased risk of UTI as the source for fever compared to girls (Shaikh et al., 2008). Other significant risk factors for UTI during childhood include bladder bowel dysfunction and congenital anomalies of the kidneys and the urinary tract (Conway et al., 2007;Shaikh et al., 2010;Mattoo et al., 2021). In children under 19 years of age and older than 2 years of age, the overall prevalence was 7.8% (Shaikh et al., 2008). ...
Article
Full-text available
Urinary tract infections (UTIs) are a significant clinical problem that pregnant women and children commonly experience. Escherichia coli is the primary causative organism, along with several other gram-negative and gram-positive bacteria. Antimicrobial drugs are commonly prescribed to treat UTIs in these patients. Conventional treatment can range from using broad-spectrum antimicrobial drugs for empirical or prophylactic therapy or patient-tailored therapy based on urinary cultures and sensitivity to prospective antibiotics. The ongoing emergence of multi-drug resistant pathogens has raised concerns related to commonly prescribed antimicrobial drugs such as those used routinely to treat UTIs. Consequently, several natural medicines have been explored as potential complementary therapies to improve health outcomes in patients with UTIs. This review discusses the effectiveness of commonly used natural products such as cranberry juice/extracts, ascorbic acid, hyaluronic acid, probiotics, and multi-component formulations intended to treat and prevent UTIs. The combination of natural products with prescribed antimicrobial treatments and use of formulations that contained high amounts of cranberry extracts appear to be most effective in preventing recurrent UTIs (RUTIs). The incorporation of natural products like cranberry, hyaluronic acid, ascorbic acid, probiotics, Canephron® N, and Cystenium II to conventional treatments of acute UTIs or as a prophylactic regimen for treatment RUTIs can benefit both pregnant women and children. Limited information is available on the safety of natural products in these patients’ populations. However, based on limited historical information, these remedies appear to be safe and well-tolerated by patients.
... Over a half of infants with UTIs develop APN. 3 Despite prompt diagnosis and treatment with appropriate antibiotics, a population of children with APN will develop permanent renal scars, which are associated with hypertension, CKD, and, in the worst cases, ESKD. [3][4][5][6] Evidence from our laboratory, using a novel preclinical model of UPEC-mediated APN, 7 indicates dysregulated host inflammation strongly correlates with the development of renal scarring during APN. ...
... Over a half of infants with UTIs develop APN. 3 Despite prompt diagnosis and treatment with appropriate antibiotics, a population of children with APN will develop permanent renal scars, which are associated with hypertension, CKD, and, in the worst cases, ESKD. [3][4][5][6] Evidence from our laboratory, using a novel preclinical model of UPEC-mediated APN, 7 indicates dysregulated host inflammation strongly correlates with the development of renal scarring during APN. These findings suggest the inflammatory response elicited during APN largely contributes to kidney fibrosis. ...
Conference Paper
Full-text available
Every year, pediatric urinary tract infections (UTI) account for 1.5 million clinician visits in the US alone. Up to 50% of infants with UTI develop a kidney infection (acute pyelonephritis, APN). Despite antibiotic therapy, 15% of children with APN develop renal scarring, which is associated with deterioration in kidney function. Here, we determined the contribution of macrophages and neutrophils to bacterial clearance and the development of kidney fibrosis during experimental APN. Female C3H/HeOuJ mice were treated, via retro-orbital, with one of the following antibodies: isotype IgG (control), anti-Ly6G (depletes neutrophils), anti-CD115 (depletes monocytes), and anti-GR1 (depletes monocytes and neutrophils). After cell depletion, the animals were transurethrally infected with UPEC. Ascending UTI was evaluated via biophotonic imaging. The dynamics of monocytes and neutrophils were determined by flow cytometry. Histopathological scores were performed by H&E and Sirius-Red stainings. Transcriptomic analyses of kidneys were performed using TaqMan Arrays. Our data indicate that neutrophils are required for bacterial clearance, while macrophages promote inflammation in the infected urinary tract. However, the absence of neutrophils results in increased macrophage infiltration and exaggerated macrophage-dependent inflammatory responses in the bladder and kidney. Also, our results demonstrate that macrophage-dependent inflammation during APN, leads to renal scarring and renal functional impairment. These findings uncover a role for the neutrophil-macrophage imbalance in promoting kidney fibrosis during APN. This knowledge will be helpful to develop novel therapies to prevent post-APN scarring in children.
... Over a half of infants with UTIs develop APN. 3 Despite prompt diagnosis and treatment with appropriate antibiotics, a population of children with APN will develop permanent renal scars, which are associated with hypertension, CKD, and, in the worst cases, ESKD. [3][4][5][6] Evidence from our laboratory, using a novel preclinical model of UPEC-mediated APN, 7 indicates dysregulated host inflammation strongly correlates with the development of renal scarring during APN. ...
... Over a half of infants with UTIs develop APN. 3 Despite prompt diagnosis and treatment with appropriate antibiotics, a population of children with APN will develop permanent renal scars, which are associated with hypertension, CKD, and, in the worst cases, ESKD. [3][4][5][6] Evidence from our laboratory, using a novel preclinical model of UPEC-mediated APN, 7 indicates dysregulated host inflammation strongly correlates with the development of renal scarring during APN. These findings suggest the inflammatory response elicited during APN largely contributes to kidney fibrosis. ...
Article
Full-text available
Background In children, the acute pyelonephritis that can result from urinary tract infections (UTIs), which commonly ascend from the bladder to the kidney, is a growing concern because it poses a risk of renal scarring and irreversible loss of kidney function. To date, the cellular mechanisms underlying acute pyelonephritis–driven renal scarring remain unknown. Methods We used a preclinical model of uropathogenic Escherichia coli–induced acute pyelonephritis to determine the contribution of neutrophils and monocytes to resolution of the condition and the subsequent development of kidney fibrosis. We used cell-specific monoclonal antibodies to eliminate neutrophils, monocytes, or both. Bacterial ascent and the cell dynamics of phagocytic cells were assessed by biophotonic imaging and flow cytometry, respectively. We used quantitative RT-PCR and histopathologic analyses to evaluate inflammation and renal scarring. Results We found that neutrophils are critical to control bacterial ascent, which is in line with previous studies suggesting a protective role for neutrophils during a UTI, whereas monocyte-derived macrophages orchestrate a strong, but ineffective, inflammatory response against uropathogenic, E. coli–induced, acute pyelonephritis. Experimental neutropenia during acute pyelonephritis resulted in a compensatory increase in the number of monocytes and heightened macrophage-dependent inflammation in the kidney. Exacerbated macrophage-mediated inflammatory responses promoted renal scarring and compromised renal function, as indicated by elevated serum creatinine, BUN, and potassium. Conclusions These findings reveal a previously unappreciated outcome for neutrophil-macrophage imbalance in promoting host susceptibility to acute pyelonephritis and the development of permanent renal damage. This suggests targeting dysregulated macrophage responses might be a therapeutic tool to prevent renal scarring during acute pyelonephritis.
... Although most have excellent prognosis, in case of renal parenchymal involvement, defined as acute pyelonephritis (APN), it leads to increased associated morbidity. In up to 15% of these patients, parenchymal damage can be permanent, known as RS [2,3], which may lead to developing proteinuria, high blood pressure and chronic renal failure in the future [4,5]. ...
... After hospital discharge, all patients were followed up. Since the absence of acute parenchymal damage allows to assume the absence of RS development [3], follow-up DMSA scans were only made in patients diagnosed with APN, and at least 9 months after the acute infection. ...
Article
Full-text available
Background Midregional-proadrenomedullin (MR-proADM) is a useful prognostic peptide in severe infectious pathologies in the adult population. However, there are no studies that analyze its utility in febrile urinary tract infection (fUTI) in children. An accurate biomarker would provide an early detection of patients with kidney damage, avoiding other invasive tests like renal scintigraphy scans. Our objective is to study the usefulness of MR-proADM as a biomarker of acute and chronic renal parenchymal damage in fUTI within the pediatric population. Methods A prospective cohort study was conducted in pediatric patients with fUTI between January 2015 and December 2018. Plasma and urine MR-proADM levels were measured at admission in addition to other laboratory parameters. After confirmation of fUTI, renal scintigraphy scans were performed during the acute and follow-up stages. A descriptive study has been carried out and sensitivity, specificity and ROC curves for MR-proADM, C-reactive protein, and procalcitonin were calculated. Results 62 pediatric patients (34 female) were enrolled. Scintigraphy showed acute pyelonephritis in 35 patients (56.5%). Of those patients, the median of plasmatic MR-proADM (P-MR-proADM) showed no differences compared to patients without pyelonephritis. 7 patients (11.3%) developed renal scars (RS). Their median P-MR-proADM levels were 1.07 nmol/L (IQR 0.66–1.59), while in patients without RS were 0.48 nmol/L (0.43–0.63) ( p < 0.01). The AUC in this case was 0.92 (95% CI 0.77–0.99). We established an optimal cut-off point at 0.66 nmol/L with sensitivity 83.3% and specificity 81.8%. Conclusion MR-ProADM has demonstrated a poor ability to diagnose pyelonephritis in pediatric patients with fUTI. However, P-MR-proADM proved to be a very reliable biomarker for RS prediction.
... It is estimated that 8-10% of girls and 2-3% of boys will suffer from a symptomatic urinary infection before the age of 7 [3][4][5][6][7][8]. Between 50 and 80% of patients with febrile UTI have acute pyelonephritis (APN) [9]. ...
... It is postulated that both acute kidney injury and scarring appear as a consequence of the inflammatory and immunological response triggered to eradicate kidney tissue infection through the activation of inflammatory mediators such as cytokines [10,11]. The incidence of permanent kidney scarring after APN is highly variable (10-60%) [9,[12][13][14]. ...
Article
Full-text available
Background Urinary tract infection (UTI) is one of the most common bacterial infections in childhood and is associated with long-term complications. We aimed to assess the effect of adjuvant dexamethasone treatment on reducing kidney scarring after acute pyelonephritis (APN) in children. Methods Multicenter, prospective, double-blind, placebo-controlled, randomized clinical trial (RCT) where children from 1 month to 14 years of age with proven APN were randomly assigned to receive a 3-day course of either an intravenous corticosteroid (dexamethasone 0.30 mg per kg/day) twice daily or placebo. The late technetium 99 m-dimercaptosuric acid scintigraphy (> 6 months after acute episode) was performed to assess kidney scar persistence. Kidney scarring risk factors (vesicoureteral reflux, kidney congenital anomalies, or urinary tract dilatation) were also assessed. Results Ninety-one participants completed the follow-up and were finally included (dexamethasone n = 49 and placebo n = 42). Both groups had similar baseline characteristics. Twenty participants showed persistent kidney scarring after > 6 months of follow-up without differences in incidence between groups (22% and 21% in the dexamethasone and placebo groups, p = 0.907). Renal damage severity in the early DMSA (β = 0.648, p = 0.023) and procalcitonin values (β = 0.065 p = 0.027) significantly modulated scar development. Vesicoureteral reflux grade showed a trend towards significance (β = 0.545, p = 0.054), but dexamethasone treatment showed no effect. Conclusion Dexamethasone showed no effect on reducing the risk of scar formation in children with APN. Hence, there is no evidence for an adjuvant corticosteroid treatment recommendation in children with APN. However, the study was limited by not achieving the predicted sample size and the expected scar formation. Trial registration Clinicaltrials.gov, NCT02034851. Registered in January 14, 2014. Graphical abstract “A higher resolution version of the Graphical abstract is available as Supplementary information.”
... Although most have excellent prognosis, when there is renal parenchymal involvement, defined as acute pyelonephritis (APN), it leads to increased associated morbidity. In up to 15% of these patients, parenchymal damage can be permanently established, known as RS [2,3] which may lead to developing proteinuria, high blood pressure and chronic renal failure in the future [4,5]. ...
... After hospital discharge, all patients were followed up. Since the absence of acute parenchymal damage allows to assume the absence of RS development [3], chronic DMSA scans were only made in patients diagnosed of APN, and at least 9 months after the acute infection. ...
Preprint
Full-text available
Background: Midregional-proadrenomedullin (MR-proADM) is a useful prognostic peptide in severe infectious pathologies in the adult population. However, there are no studies that analyze its utility in febrile urinary tract infection (fUTI) in children. An accurate biomarker would provide an early detection of patients with kidney damage, avoiding other invasive tests like renal scintigraphy scans. Our objective is to study the usefulness of MR-proADM as a biomarker of acute and chronic renal parenchymal damage in fUTI within the pediatric population. Material and Methods: A prospective cohort study was conducted in pediatric patients with fUTI between January 2015 and December 2018. Plasma and urine MR-proADM levels were measured at admission in addition to other laboratory parameters. After confirmation of fUTI, renal scintigraphy scans were performed during the acute and chronic stages. A descriptive study has been carried out and sensitivity, specificity and ROC curves for MR-proADM, C-reactive protein, and procalcitonin were calculated. Results: 62 pediatric patients (34 women) were enrolled. Scintigraphy showed acute pyelonephritis in 35 patients (56.5%). Of those patients, median of plasmatic MR-proADM (P-MR-proADM) showed no differences compared to patients without pyelonephritis. 7 patients (11.3%) developed renal scars (RS). Their median P-MR-proADM levels were 1.07 nmol/L (IQR 0.66 – 1.59), while in patients without RS were 0.48 nmol/L (0.43 – 0.63) (p<0.01). The AUC in this case was 0.92 (95% CI 0.77 – 0.99). We stablished an optimal cut-off point at 0.66 nmol/L with sensitivity 83.3% and specificity 81.8%. Conclusion: MR-ProADM has a poor ability to diagnose pyelonephritis in pediatric patients with fUTI. However, P-MR-proADM showed as a very reliable biomarker for RS prediction. Keywords: Proadrenomedullin, biomarker, urinary tract infection, pediatric, renal scarring
... As seen in VUR studies in the literature and in the present study, the rate of scarring increased as the grade of reflux increased (Fig 3). However, not all patients with high-grade reflux develop renal scarring and those with low-grade reflux can also develop renal scars since the inflammatory process and immune response progress differently in each patient [17,31]. In the sub-data analysis of our study, the lymphocyte count was significantly higher (p < 0.05) and the neutrophil count and NLR were significantly lower (p < 0.05) in patients with renal scarring who had high-grade (grades IV-V) reflux than in those without renal scarring. ...
... VUR occurs in 24%-39% of patients with acute pyelonephritis detected by DMSA scintigraphy [32]. In a systematic review by Shaikh et al., DMSA changes were found in the acute phase in 57% of the patients after the first UTI episode and these changes were observed in 15% of the patients during follow-up [31]. Therefore, repeat DMSA imaging 6-12 months later is recommended to determine the long-term outcomes in patients with signs of acute pyelonephritis [33]. ...
Preprint
Aim: Vesicoureteral reflux (VUR) exacerbates the risk of renal scarring by establishing a ground for pyelonephritis. It is known that the inflammatory process is more influential than the direct damage caused by bacterial infection in the development of renal scars after pyelonephritis. Therefore, the present study aims to investigate the relationship between renal scarring and systemic inflammatory markers in patients with VUR. Methods: Hundred and ninety-two patients (116 girls, 76 boys) diagnosed with VUR were divided into two groups based on the presence or absence of renal scarring and into three groups according to the grade of VUR (low, moderate and high). Neutrophil count, lymphocyte count, mean platelet volume (MPV) and neutrophil-to-lymphocyte ratio (NLR) were compared among the groups. Results: Of the 192 patients, 102 had renal scarring. The age and gender distribution did not differ significantly between the groups with and without renal scarring (p > 0.05). However, the grade of reflux and lymphocyte count were significantly higher in the group with renal scarring (p < 0.05), and the NLR was significantly lower in the group with renal scarring (p < 0.05). The lymphocyte count was significantly higher (p <0.05) and NLR was significantly lower in the high-grade VUR group (p < 0.05). However, MPV values did not differ significantly (p > 0.05) between the groups. Conclusion: NLR can be used to predict renal scarring in patients with VUR and may even serve as a candidate marker for treatment selection. However, larger series and prospective studies are needed. Keywords: vesicoureteral reflux, neutrophil-to-lymphocyte ratio, pyelonephritis, renal scarring
... As seen in VUR studies in the literature and in the present study, the rate of scarring increased as the grade of reflux increased ( Figure 3). However, not all patients with high-grade reflux develop renal scarring and those with low-grade reflux can also develop renal scars since the inflammatory process and immune response progress differently in each patient (17,32). In the subdata analysis of our study, the lymphocyte count was significantly higher (p < 0.05) and the neutrophil count and NLR were significantly lower (p < 0.05) in patients with renal scarring who had high-grade (grades IV-V) reflux than in those without renal scarring. ...
... VUR occurs in 24%-39% of patients with acute pyelonephritis detected by DMSA scintigraphy (33). In a systematic review by Shaikh et al., DMSA changes were found in the acute phase in 57% of the patients after the first UTI episode and these changes were observed in 15% of the patients during follow-up (32). Therefore, repeat DMSA imaging 6-12 months later is recommended to determine the long-term outcomes in patients with signs of acute pyelonephritis (34). ...
Article
Full-text available
Objectives: Vesicoureteral reflux (VUR) exacerbates the risk of renal scarring by establishing a ground for pyelonephritis. It is known that the inflammatory process is more influential than the direct damage caused by bacterial infection in the development of renal scars after pyelonephritis. Therefore, the present study aims to investigate the relationship between renal scarring and systemic inflammatory markers in patients with VUR. Material and methods: Hundred and ninety-two patients (116 females, 76 males) diagnosed with VUR were divided into two groups based on the presence or absence of renal scarring and into three groups according to the grade of VUR (low, moderate and high). Neutrophil count, lymphocyte count, mean platelet volume (MPV) and neutrophil-to-lymphocyte ratio (NLR) were compared among the groups. Results: Of the 192 patients, 102 had renal scarring. The age and gender distribution did not differ significantly between the groups with and without renal scarring (p > 0.05). However, the grade of reflux and lymphocyte count were significantly higher in the group with renal scarring (p < 0.05), and the NLR was significantly lower in the group with renal scarring (p < 0.05). The lymphocyte count was significantly higher (p < 0.05) and NLR was significantly lower in the high-grade VUR group (p < 0.05). However, MPV values did not differ significantly (p > 0.05) between the groups. Conclusions: NLR can be used to predict renal scarring in patients with VUR, especially in the period of 3-6 months after the first attack of infection, and may even serve as a candidate marker for treatment selection. However, larger series and prospective studies are needed.
... Studies reported that UTI accounted for 12.9, 19.6, and 11.3% of nosocomial infections in the United States, Europe, and China, respectively (2,3). Recurrent infection occurred in ∼8% of children who experienced a first episode of UTI (4). Among recurring cases, approximately 17.5% occurred during the first 3 months, and 53% occurred within 9-12 months following the initial infection (5). ...
Article
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Background Urinary tract infection (UTI) is a common complication in pediatric urological surgery patients and is associated with long-term sequelae, including subsequent recurrent infections and renal scarring. In this study, we aimed to explore the risk factors for UTI in pediatric urological surgery patients and construct a predictive model for UTI.Materials and MethodsA total of 2,235 pediatric patients who underwent urological surgery at a tertiary hospital between February 2019 and January 2020 were included. A multivariate logistic regression model was applied to identify the predictive factors, and a predictive model was constructed using a receiver operating characteristic curve. A multifactorial predictive model was used to categorize the risk of UTI based on the weight of the evidence.ResultsA total of 341 patients with UTI were identified, which corresponded to a prevalence of 15.26% in pediatric urological surgery patients. Multivariate analysis identified six significant risk factors for UTI, including age <12.0 months, upper urinary tract disease, not using an indwelling drainage tube, hospital stay ≥10 days, administration of two or more types of antibiotics, and stent implantation. A combination of the aforementioned factors produced an area under the curve value of 88.37% for preventing UTI in pediatric urological surgery patients. A multifactorial predictive model was created based on the combination of these factors.Conclusions The constructed multifactorial model could predict UTI risk in pediatric urological surgery patients with a relatively high predictive value.
... Renal scars are present in 6.1% children with UTI. 5 The first episode of UTI in infants should be investigated and followed up well to prevent renal scarring later. 6 The advantages of using 99mTc-DMSA renal scintigraphy to evaluate renal scarring have been confirmed in various studies. [7][8][9] They demonstrated the efficiency of this imaging modality for clinical use compared to conventional imaging techniques such as ultrasound, CT and MRI methodology. ...
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Background: The aim of the study was to determine the risk factors for renal scarring detected by DMSA (dimercaptosuccinic acid) scan in children with culture-proven urinary tract infection (UTI).Methods: A hospital based observational case-control study was conducted from 2018 June to 2020 June in children aged between 1 month to 5 years who underwent a DMSA scan following culture-proven UTI (N=72). Of the children fulfilling the criteria, 43 had renal scarring in the DMSA scan as a case group and the remaining 29 children who had no renal scarring were taken as a control group.Results: Of the total 72 cases with culture-positive UTI, 59% of patients had renal scarring and the rest and 40% were scar negative. There was no significant difference in the renal scarring observed with respect to age in the two groups. There was significant (p<0.05) the association noted between renal scarring and VUR (vesicoureteric reflux). A significant difference was observed in the renal scarring between the two groups regarding the presence of recurrent UTI (p=0.000). Although most cases (97.7%) had a fever in the DMSA positive group, this was not a significant risk factor for scarring (p>0.05). In DMSA positive group, circumcision was not a significant risk factor for scarring.Conclusions: VUR and recurrent UTI were significant risk factors for renal scarring in children with culture-proven UTI as detected by DMSA scan. The other risk factors like age, sex, fever, leucocytosis and circumcision were not found to be significant.
... Urinary tract infection (UTI) is one of the most common bacterial infections in childhood [1], and approximately 17% of children without vesicoureteral reflux (VUR), and 25% of children with VUR, will experience a recurrent febrile infection within the first 2 years after initial UTI [2]. AP, also termed 'upper UTI', can be a serious infection in children involving the upper urinary tract and kidney parenchyma and might eventually lead to kidney scarring [3], kidney injury and hypertension [4]. Escherichia Coli (E. ...
Article
Background Acute pyelonephritis (AP) is a common bacterial infection in childhood. Follow-up guidelines on these children are controversial. This study aimed to identify risk factors for kidney scarring and vesicoureteral reflux (VUR). Furthermore, international follow-up guidelines were used for simulation to evaluate sensitivity and specificity.Methods Urinary culture-confirmed first-time AP patients (aged 0–14 years) were enrolled (n = 421) from review of patient charts. All underwent kidney ultrasound (US) and a technetium-99m-dimercaptosuccinic acid (DMSA) scan or technetium-99m-mercaptoacetyltriglycine scinti-renography (MAG3) at 4–6 months of follow-up. The international guidelines used for simulation were from the National Institute of Health UK (NICE), the American Association of Paediatrics (AAP) and the Swedish Paediatric Society (SPS).Results17.8% presented with an abnormal DMSA/MAG3 at follow-up, 7.1% were diagnosed with VUR grades III–V and 4.7% were admitted for surgery. Non-Escherichia coli infections, abnormal kidney US, elevated creatinine and delayed response to treatment (>48 h) were risk factors for abnormal DMSA findings and VUR grades III–V. NICE and SPS guidelines showed best sensitivity in diagnosing VUR grades III–V (75%) compared with AAP (56%).Conclusions Risk factors are helpful in identifying the children in need of further investigations and minimizing invasive work-up for the rest. International guidelines on follow-up detect a varying number of children with kidney damage and/or significant VUR. Future work must focus on identifying more specific risk factors, better imaging, or specific biomarkers, to enhance sensitivity and specificity in detecting the children at high risk for developing recurrent infections and/or nephropathy.
... The absence of urinary symptoms distinguishes ASB from UTI. ASB, unlike urinary tract infection, does not require the use of antibiotics 7,8 . The use of antibiotics in UTI is important as up to 15% of children who were reported to have UTI for the first time were showing evidence of renal scarring on dimercaptosuccinic acid scan with a potential to develop hypertension 9 . Nader Shaikh et al in their meta-analysis of fourteen articles reporting data on asymptomatic bacteriuria in children noted that the prevalence of ASB was 0.37% (95% CI,0.09-0.82) in boys and 0.47% (95% CI, 0.36-0.59) in girls with the highest prevalence seen in uncircumcised males<1year and females>2 years 10 . ...
Article
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Introduction: Urinary tract infection (UTI) is often seen in paediatric patients. The aim of this study was to determine the prevalence and clinical characteristics of UTI in children attending the Paediatrics Department of Ekiti State University Teaching Hospital (EKSUTH), Ado-Ekiti Methods: A cross sectional study was carried out among consecutive children with age ≤ 15 years presenting over a period of 6months (from September 2019 to February 2020) at the outpatient (OPD) and children emergency ward (CEW) of Ekiti State University Teaching Hospital, Ado Ekiti, Nigeria. Ethical approval from the institution and parental informed consent were obtained. Patients' bio-data, history and clinical findings were entered in a structured proforma and 5-10mls of mid-stream urine was collected for urinalysis, microscopy, culture and sensitivity. Results: The prevalence of UTI among the subjects was 11% with female preponderance. The mean age was 80.44± 48.73 months. Fever was the most common presenting complaint while malaria fever was the initial diagnosis in 11(45.8%) subjects and asymptomatic bacteriuria was found in 2(8.3%). Escherichia coli had the highest frequency of 11(45.8%) in this study followed by Staphylococcus aureus (4;16.7%) and Klebsiella (4;16.7%), and was sensitive to the quinolones (ciprofloxacin and ofloxacin). Resistance to the following antibiotics were observed; amoxicillin/clavulanic acid, ceftazidime, ceftriaxone and cefuroxime. Conclusions: The prevalence of UTI among the studied population is high. Urine laboratory tests should be done routinely in febrile children, while common causative organism such as Escherichia coli should be considered for empirical treatment with quinolones.
... Renal scarring in late DMSA scan is seen in about 15% of children following the first episode of febrile UTI. 2 Long-term (10-40 years) follow-up studies have shown that the acquired renal scarring might increase the risk for hypertension, proteinuria in adulthood and rarely results in end-stage renal disease too (specially in individuals with bilateral renal scarring). [3][4][5][6][7] Kidney scarring is speculated to be caused by the ongoing inflammatory process rather than the bacterial invasion of renal parenchyma. ...
Article
Background Acute pyelonephritis in children may result in permanent kidney scarring that is primarily caused by inflammation during acute infection. Antibiotic therapy alone is not enough to significantly reduce kidney scarring, and adjuvant corticosteroid therapy has shown a significant reduction in inflammatory cytokines in urine prompting its evaluation in randomised controlled trials. A few clinical trials showed a trend towards a reduction in renal scarring but did not have an adequate sample size to show a significant effect. Therefore, we planned to synthesise the available evidence on the role of corticosteroids as adjuvant therapy in reducing kidney scarring. Objective To assess the efficacy and safety of adjuvant corticosteroid therapy for the prevention of kidney scarring in children with acute pyelonephritis. Design Systematic review and meta-analysis. Setting Community-acquired febrile urinary tract infections. Patients Children (less than 18 years) with acute pyelonephritis. Intervention Adjuvant corticosteroid therapy (along with antibiotic treatment). Main outcome measures Primary: efficacy in preventing kidney scarring; secondary: serious adverse events associated with corticosteroid therapy. Results Three randomised trials (529 children) were included. Corticosteroids are effective in lowering the risk of kidney scarring as compared with placebo (risk ratio (RR): 0.57; 95% CI 0.36 to 0.90). No significant increase risk of bacteraemia (RR: 1.38; 95% CI 0.23 to 8.23) and hospitalisation (RR: 0.87; 95% CI 0.3 to 2.55) was observed in corticosteroid group. Conclusion Moderate quality evidence suggests that short duration ‘adjuvant corticosteroid therapy’ along with routine antibiotic therapy in acute febrile urinary tract infection significantly reduces the risk of kidney scarring without any significant adverse effects.
... Paediatric urinary tract infections (UTI) could be considered serious since they may trigger systemic infection and result in kidney scarring [1]. UTIs occur in nearly 6% of all acutely ill children presenting to ambulatory care [2]. ...
Article
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Background Accurate diagnosis of urinary tract infection is essential as children left untreated may suffer permanent renal injury. Aim To compare the diagnostic values of biomarkers or clinical prediction rules for urinary tract infections in children presenting to ambulatory care. Design and setting Systematic review and meta-analysis of ambulatory care studies. Methods Medline, Embase, WOS, CINAHL, Cochrane library, HTA and DARE were searched until 21 May 2021. We included diagnostic studies on urine or blood biomarkers for cystitis or pyelonephritis in children below 18 years of age. We calculated sensitivity, specificity and likelihood ratios. Data were pooled using a bivariate random effects model and a Hierarchical Summary Receiver Operating Characteristic analysis. Results Seventy-five moderate to high quality studies were included in this review and 54 articles in the meta-analyses. The area under the receiver-operating-characteristics curve to diagnose cystitis was 0.75 (95%CI 0.62 to 0.83, n = 9) for C-reactive protein, 0.71 (95% CI 0.62 to 0.80, n = 4) for procalcitonin, 0.93 (95% CI 0.91 to 0.96, n = 22) for the dipstick test (nitrite or leukocyte esterase ≥trace), 0.94 (95% CI 0.58 to 0.98, n = 9) for urine white blood cells and 0.98 (95% CI 0.92 to 0.99, n = 12) for Gram-stained bacteria. For pyelonephritis, C-reactive protein < 20 mg/l had LR- of 0.10 (95%CI 0.04–0.30) to 0.22 (95%CI 0.09–0.54) in children with signs suggestive of urinary tract infection. Conclusions Clinical prediction rules including the dipstick test biomarkers can support family physicians while awaiting urine culture results. CRP and PCT have low accuracy for cystitis, but might be useful for pyelonephritis.
... Permanent renal scarring has been observed after UTI in 15-60% of affected children [8]. To minimize such insult the early diagnosis and targeted antimicrobial therapy is crucial [9]. To arrive at a microbiological diagnosis, Royal college of physicians (United Kingdom) guideline stated that clean catch urine in an infant or a mid-stream urine specimen in an older child is the ideal for urine culture ...
Article
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Background In children, urinary tract infection (UTI) is one of a common bacterial infection. This study was conducted to detect the uropathogen, antimicrobial susceptibility, pathogen associated with recurrences and renal scarring in children initially taken care from general practitioners and later presented to tertiary care. Methods Every inward UTI episode, culture and antimicrobial susceptibility was done while on past 6-month, history of infections and use of antimicrobials was collected using clinical records and demonstration of antimicrobials. Children with recurrent pyelonephritis was followed and in vitro bio film formation was assessed. Results Frequency of UTI was significantly high among infants (p = 0.03). Last 6-month, all (220) were exposed to antimicrobials. Cefixime was the commonly prescribed antimicrobial (p = 0.02). In current UTI episode, 64.5% (142/220) of children with UTI were consulted GPs’ prior to seek treatment from tertiary care pediatric unit (p = 0.02). While on follow up child who developed UTI, found urine culture isolates were significantly shifted from E. coli and K. pneumoniae to extended spectrum of beta-lactamase (ESBL) E. coli and K. pneumoniae. Out of 208 participants, 36 of them had re-current pyelonephritis (R-PN). Renal scarring (RS) was detected in 22 out of 70 patients with pyelonephritis following dimercaptosuccinic acid scan. Following each episodes of recurrent pyelonephritis 11% of new scar formation was detected (p = 0.02). Bio film forming E. coli and K. pneumoniae was significantly associated in patients with R-PN (p = 0.04). Discussion Medical care providers often prescribe antimicrobials without having an etiological diagnosis. While continuing exposure of third generation cephalosporin and carbapenem leads to development of ESBL and CRE microbes in great. The empiric uses of antimicrobials need to be stream lined with local epidemiology and antimicrobial susceptibility pattern. R-PN in childhood leads to RS. In great, bio film formation act as the focus for such recurrences.
... However, it is still controversial whether or not renal scarring develops due to VUR. Shaikh et al describe that renal scarring could develop in patients with LUTD in the absence of VUR.42 Some experimental data of monkeys showed that the hematogenous spread of infections, such as ascending pyelonephritis, in the absence of VUR may play a role in the development of renal scarring.43 ...
Objectives: Functional urinary incontinence is often associated with recurrent urinary tract infection (UTI), vesicoureteral reflux (VUR), and renal scarring. This study aims to evaluate the correlations between urodynamic findings and recurrence of UTI, VUR, and renal scarring in children with functional incontinence. Methods: In this retrospective observational study, data on the presence of VUR, urodynamics and 99Tc-dimercaptosuccinic acid scintigraphy findings, and episodes of febrile UTI were obtained from patients' records. The patients had at least 3 years of follow-up. Results: There were significant associations between recurrence of UTI and decreased bladder capacity (hazard ratio: 1.321, P = .028). The receiver operator characteristic curve analysis showed a cutoff value for compliance of 13.25 mL/cmH2 O for renal scarring (P = .000). There was a significant association between bladder wall thickening and VUR (odds ratio: 2.311, P = .008). The compliance had a cutoff value of 14.7 mL/cm H2 O (P = .023) for severe VUR. The frequency of renal scarring was higher in patients with severe VUR and dysfunctional voiding (P = .001 and P = .041, respectively). The independent risk factors for renal scarring were low compliance, severe VUR, and dysfunctional voiding in children with functional incontinence, but recurrence of febrile UTI was not a risk factor for renal scarring. Decreased bladder capacity was a risk factor for recurrence of febrile UTI. Conclusions: The present study suggests that low compliance, severe VUR, and dysfunctional voiding, but not the recurrence of febrile UTI, are the independent risk factors for renal scarring in children with functional incontinence, and decreased bladder capacity is the risk factor for the recurrence of febrile UTI.
... Given the low rate of UTI reported, it may be considered that antibiotic prophylaxis has a limited role in the management of such patients (13,(47)(48)(49), and VCUG screening is considered to be optional (50). However, more aggressive evaluation and intervention, including antibiotic prophylaxis and VCUG are often indicated in those with worsening or high-grade hydronephrosis (47,(51)(52)(53). It should be noted that the presence of ureter dilatation is also important to suspect VUR even in severe hydronephrosis cases. ...
Article
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The most common cause of hydronephrosis in the pediatric age group is ureteropelvic junction-type hydronephrosis (UPJHN). Since the advent of widespread maternal ultrasound screening, clinical presentation of hydronephrosis associated with UPJ anomalies has changed dramatically. Today most cases are diagnosed in the prenatal period, and neonates present without signs or symptoms. For those who are not detected at birth, UPJHN eventually presents throughout childhood and even adulthood with various symptoms. Clinical picture of UPJHN highly depends on the presence and severity of obstruction, and whether it affects single or both kidneys. Abdominal or flank pain, abdominal mass, hematuria, kidney stones, urinary tract infections (UTI), and gastrointestinal discomfort are the main symptoms of UPJHN in childhood. Other less common findings in such patients are growth retardation, anemia, and hypertension. UTI is a relatively rare condition in UPJHN cases, but it may occur as pyelonephritis. Vesicoureteric reflux should be kept in mind as a concomitant pathology in pediatric UPJHN that develop febrile UTI. Although many UPJHN cases are known to improve over time, close clinical observation is critical in order to avoid irreversible kidney damage. The most appropriate approach is to follow-up the patients considering the presence of symptoms, the severity of hydronephrosis and the decrease in kidney function and, if necessary, to decide on early surgical intervention.
... UTIs are not trivial infections, with detectable bacteraemia of the same organism in 10% of cases, rising to 17% in those < 1 month old [3]. 2.8-16% of individuals may develop kidney scarring following their first episode of UTI, with 8.4% of these developing hypertension, and a small proportion progressing to kidney failure [6][7][8]. Kidney scarring and damage can be prevented if UTI is treated in a timely manner, with delay leading to increasingly likely scarring [9,10]. ...
Article
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Urinary tract infection is a commonly occurring paediatric infection associated with significant morbidity. Diagnosis is challenging as symptoms are non-specific and definitive diagnosis requires an uncontaminated urine sample to be obtained. Common techniques for sampling in non-toilet-trained children include clean catch, bag, pad, in-out catheterisation and suprapubic aspiration. The pros and cons of each method are examined in detail in this review. They differ significantly in frequency of use, contamination rates and acceptability to parents and clinicians. National guidance of which to use differs significantly internationally. No method is clearly superior. For non-invasive testing, clean catch sampling has a lower likelihood of contamination and can be made more efficient through stimulation of voiding in younger children. In invasive testing, suprapubic aspiration gives a lower likelihood of contamination, a high success rate and a low complication rate, but is considered painful and is not preferred by parents. Urine dipstick testing is validated for ruling in or out UTI provided that leucocyte esterase (LE) and nitrite testing are used in combination.
... Bu nedenle hastaların çoğunda VÜR'ün ilk tanısı ateşli bir İYE'den sonra ortaya çıkar. 26,27 İdrar yolu enfeksiyonu sonrası VÜR tanısı alan çocukların çoğunluğu ise kızdır. Ancak 6 aylıktan küçük bebeklerde cinsiyet farkı belirgin değildir. ...
Chapter
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Vezikoüreteral reflü (VÜR), idrarın mesaneden üreterler ve böbreklere doğru geri akımı olarak tanımlanır. Çocukluk çağının en sık görülen konjenital ano-malilerinden biridir. Böbrek hasarına neden olması ve çocukluk çağı kronik böbrek yetmezliğinin etyolojik nedenleri arasında ilk sırada yer alması nedeniyle de önemlidir. 1 Ülkemizde 2009 yılında yapılan çok merkezli çalışmada, kronik böbrek yet-mezliği olan çocuklarda %18 sıklığı ile ilk sıradaki etyolojik neden olduğu gösterilmiş-tir. 2 Günümüzde VÜR'ün tanısı, medikal ve cerrahi tedavisi hakkında çok şey bilinmesine rağmen, böbrek hasarına neden olma potansiyeli ile ilgili birçok soru bu-lunmaktadır. Bu bölümde VÜR ile ilgili güncel bilgiler, devam eden tartışmalar, tanı ve tedavi uygulamaları gözden geçirilecektir. ETYOLOJİ VE EPİDEMİYOLOJİ Primer VÜR üreterovezikal bileşkedeki doğumsal anomalilere bağlı oluşur. Sekonder VÜR ise böbrek ve idrar yollarının diğer konjenital anomalileri ve mesanenin fonksiyon 43 Vezikoüreteral Reflü Vesicoureteral Reflux ÖZET Vezikoüreteral reflü (VÜR), Çocukluk çağının en sık görülen konjenital anomalilerinden biridir. Çocukluk çağı kronik böbrek yetmezliğinin etyolojik nedenleri arasında ilk sırada yer alması nedeniyle önemlidir. Vezikoüreteral reflü asemptomatik olabileceği gibi, idrar yolu enfeksiyonu ve/veya alt üriner sistem disfonksiyonu bulguları ile karşımıza çıkabilir. Renal hasarlanmanın geliştiği hastalarda protei-nüri, hipertansiyon ve/veya kronik böbrek yetmezliği bulguları görülebilir. Günümüzde VÜR tanısı, me-dikal ve cerrahi tedavisi hakkında yoğun çalışmalar yapılmasına rağmen, reflünün böbrek hasarına neden olma potansiyeli ile ilgili çeşitli soru işaretleri bulunmaktadır. Vezikoüreteral reflü özellikle düşük de-receli ise zaman içinde hastaların önemli bir bölümünde kendiliğinden düzelebilir. Bu nedenle güncel tar-tışmalar vezikoüreteral reflünün ne zaman hastaya zarar verme potansiyeli olan patolojik durum olarak kabul edileceği üzerine yoğunlaşmıştır. Bu bağlamda VÜR sekelleri açısından riski olan hastaları ta-nımlamak ve hastalığın tedavisini buna göre planlamak önemlidir. Anah tar Ke li me ler: CAKUT; vezikoüreteral reflü; teknesyum Tc 99m dimerkaptosüksinik asid ABS TRACT Vesicoureteral reflux (VUR) is one of the most common congenital anomalies of childhood. Vesicoureteral reflux is one of the leading causes of childhood chronic kidney failure, therefore it is very important. Vesicoureteral reflux can be asymptomatic or may present with symptoms of urinary tract infection and/or lower urinary tract dysfunction. In patients with renal scarring, signs of proteinuria, hypertension and/or chronic renal failure may be seen. Although intensive studies are currently conducted on the diagnosis and treatment of vesicoureteral reflux, there are several questions regarding the potential of reflux to cause kidney damage. Vesicoureteral reflux can be spontaneously resolved in the majority of patients, especially if it is low grade. For this reason, current discussions have focused on where or when vesicoureteral reflux will be considered as a pathological condition. In this context, it is important to identify the patients at risk for the development of VUR sequels and to plan the treatment of this disease according to this risk assessment.
... Up to 15% of children will have permanent renal injury after a first febrile UTI. 5 This can cause impaired renal growth, recurrent pyelonephritis, renal hypertension, or end-stage renal disease, which can be prevented by prompt antibiotic treatment. [6][7][8] Urinary tract infections often remain undetected in children, especially in infants, given their inability to verbally describe symptoms and the difficulty of obtaining a clean urine sample. ...
Article
Purpose: Accurate diagnosis of urinary tract infection in children is essential because children left untreated can experience permanent renal injury. We aimed to assess the diagnostic value of clinical features of pediatric urinary tract infection. Methods: We performed a systematic review and meta-analysis of diagnostic test accuracy studies in ambulatory care. We searched the PubMed, Embase, Web of Science, Cumulative Index to Nursing and Allied Health Literature, Cochrane Central Register of Controlled Trials, Health Technology Assessment, and Database of Abstracts of Reviews of Effects databases from inception to January 27, 2020 for studies reporting 2 × 2 diagnostic accuracy data for clinical features compared with urine culture in children aged <18 years. For each clinical feature, we calculated likelihood ratios and posttest probabilities of urinary tract infection. To estimate summary parameters, we conducted a bivariate random effects meta-analysis and hierarchical summary receiver operating characteristic analysis. Results: A total of 35 studies (N = 78,427 patients) of moderate to high quality were included, providing information on 58 clinical features and 6 prediction rules. Only circumcision (negative likelihood ratio [LR-] 0.24; 95% CI, 0.08-0.72; n = 8), stridor (LR- 0.20; 95% CI, 0.05-0.81; n = 1), and diaper rash (LR- 0.13; 95% CI, 0.02-0.92; n = 1) were useful for ruling out urinary tract infection. Body temperature or fever duration showed limited diagnostic value (area under the receiver operating characteristic curve 0.61; 95% CI, 0.47-0.73; n = 16). The Diagnosis of Urinary Tract Infection in Young Children score, Gorelick Scale score, and UTIcalc (https://uticalc.pitt.edu) might be useful to identify children eligible for urine sampling. Conclusions: Few clinical signs and symptoms are useful for diagnosing or ruling out urinary tract infection in children. Clinical prediction rules might be more accurate; however, they should be validated externally. Physicians should not restrict urine sampling to children with unexplained fever or other features suggestive of urinary tract infection.
... Urinary tract infection (UTI) is the most common bacterial infection in children;in children younger than 24 months old, the prevalence of UTI was 4.5-7.2% in children with fevers.(1) Without prompt intervention, UTI may deteriorate into acute pyelonephritis (APN), renal abscess, or sepsis; furthermore, it may lead to kidney scarring, (2,3) and it is potentially related to long-term hypertension,(4) chronic kidney disease, and end-stage kidney disease. (5,6)In fact, the odds ratio of kidney scarring increases by 0.8% every hour that antibiotic intervention is delayed.(7) ...
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Background: Children with urinary tract infections (UTIs) are prone to kidney scarring if they are not treated promptly; however, ambiguous symptoms before fever onset makes the early detection of UTIs difficult. Our study aimed to identify urethral discharge as an early manifestation in children with UTI. Methods: This study enrolled 678 children younger than 24 months with paired urinalysis and culture performed between 2015 and 2021; 544 children were diagnosed with UTIs. Clinical symptoms, urinalysis, and paired urine culture results were compared. Results: Urethral discharge was observed in 5.1% of children with UTI and yielded a specificity of 92.5% for diagnosing UTI. Children with urethral discharge had a less severe UTI course, furthermore, nine of them received antibiotics before fever occurred and seven of them were free of fever during UTI course. Urethral discharge was associated with alkalotic urine and Klebsiella pneumonia infection. Conclusions: Urethral discharge is an early symptom in children with UTI; it may present before fever onset and help ensure prompt antibiotic intervention. Trial registration: Not applicable.
... Nevertheless, a number of studies suggest that resistant UTI can occur even in children without any risk factors [38]. Although the presence of resistant uropathogens is associated with poor outcomes and the risk of complications, in routine practice, the risk of serious immediate or long-term clinical problems due to discordant therapy is lower than expected [39,40]. Despite some exceptions, studies evaluating outcomes of paediatric UTIs according to the antibiotic therapy administered have shown that in a relevant number of cases, the outcome of children receiving drugs that are ineffective against the infectious pathogen in vitro did not differ from children given concordant therapy [41]. ...
Article
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The development and spread of antibiotic resistance is an increasingly important global public health problem, even in paediatric urinary tract infection (UTI). In light of the variability in the data, it is necessary to conduct surveillance studies to determine the prevalence of antibiotic resistance in specific geographical areas to optimize therapeutic management. In this observational, retrospective, multicentre study, the medical records of 1801 paediatric patients who were hospitalised for UTI between 1 January 2012, and 30 June 2020, in Emilia-Romagna, Italy, were analysed. Escherichia coli was the most frequently detected pathogen (75.6%), followed by Klebsiella pneumoniae (6.9%) and Pseudomonas aeruginosa (2.5%). Overall, 840 cases (46.7%) were due to antimicrobial-resistant uropathogens: 83 (4.7%) extended spectrum beta-lactamase (ESBL)-producing, 119 (6.7%) multidrug resistant (MDR) and 4 (0.2%) extensively drug resistant (XDR) bacteria. Empirical antibiotic therapy failed in 172 cases (9.6%). Having ESBL or MDR/XDR uropathogens, a history of recurrent UTI, antibiotic therapy in the preceding 30 days, and empirical treatment with amoxicillin or amoxicillin/clavulanate were significantly associated with treatment failure, whereas first-line therapy with third-generation cephalosporins was associated with protection against negative outcomes. In conclusion, the increase in the resistance of uropathogens to commonly used antibiotics requires continuous monitoring, and recommendations for antibiotic choice need updating. In our epidemiological context, amoxicillin/clavulanate no longer seems to be the appropriate first-line therapy for children hospitalised for UTI, whereas third-generation cephalosporins continue to be useful. To further limit the emergence of resistance, every effort to reduce and rationalise antibiotic consumption must be implemented.
... 13 Highgrade VUR and repeated pyelonephritis are considered to be the most important risk factors for renal scar development in children. [14][15][16] In addition, sex differences have been reported in the development of renal parenchymal damage, with boys tending to present antenatally or during the first year of life and often with bilateral severe VUR. 17 Girls are usually first diagnosed at an older age, and their VUR is often less severe and prone to recurrent UTIs. ...
Article
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Purpose: Children with vesicoureteral reflux (VUR) are at an increased risk of recurrent urinary tract infections (UTIs). Early detection and treatment of VUR are important to prevent renal function impairment. Therefore, the aims of this study were to determine the epidemiology of VUR and to identify clinical factors associated with VUR in Taiwanese children with a first documented UTI. Patients and methods: We conducted this nationwide retrospective study using the Longitudinal Health Insurance Database 2010. Children ≤6 years of age who were admitted and received intravenous antibiotics for a newly diagnosed UTI were included. Multivariate logistic regression analysis was used to identify independent factors associated with VUR. Results: Overall, 388 (10.2%) of the children had VUR. The median (interquartile range) age at diagnosis of VUR was 0.5 (0.3-1.3) years. Among the children with VUR, the age at first UTI and the age at diagnosis of VUR were significant lower in the males than in the females. Age ≤1 year at the first UTI (odds ratio (OR), 1.3; 95% confidence interval (CI): 1.0-1.7), renal agenesis and dysgenesis (OR, 4.1; 95% CI: 1.3-13.1), hydronephrosis (OR, 2.2; 95% CI: 1.7-2.9), duplex collecting system/ectopic kidney/ectopic ureter (OR, 13.0; 95% CI: 8.1-20.8), neuropathic bladder (OR, 4.7; 95% CI: 2.0-11.1) and spina bifida (OR, 5.9; 95% CI: 1.3-27.8) were independent factors for VUR. Conclusion: The children with VUR were more likely to have small kidneys and progression to end-stage renal disease. VUR was common in the children with a UTI and who were ≤1 year of age. Clinicians should arrange ultrasound to diagnose urinary tract anomalies. Infants with urinary tract anomalies, neuropathic bladder and spina bifida should receive further voiding cystourethrography to diagnose VUR early, as this may help to prevent renal damage.
Article
Background: Early diagnosis of pediatrics urinary tract infections in the outpatient settings is challenging but essential to prevent hospitalization and kidney damage. Objective: We aimed to evaluate the diagnostic test accuracy of a selection of point-of-care tests for pediatric urinary tract infections in general practice. Methods: A prospective cross-sectional study in 26 general practices in Flanders, Belgium (clinicaltrials.gov, NCT03835104). Urine was sampled systematically from children between 3 months to 18 years presenting with an acute illness of maximum 10 days. Samples were analyzed at the central laboratory with a routine dipstick test, the Utriplex test, the Uriscreen test and the Rapidbac as index tests, and with urine culture showing more than 105 colony-forming units per milliliter of one pathogen as reference standard. For each test, we calculated sensitivity, specificity, positive and negative likelihood ratios, and predictive values with 95% confidence intervals. Results: Three-hundred urine samples were available for analysis of which 30 samples were culture positive (10%). Sensitivities and specificities were 32% (95% CI 16%-52%) and 86% (95% CI 82%-90%) for the dipstick test, 21% (95% CI 8%-40%) and 94% (95% CI 91%-97%) for the Utriplex test, 40% (95% CI 16%-68%) and 83% (95% CI 75%-88%) for the Rapidbac test, and 67% (95% CI 38%-88%) with 69% (95% CI 60%-76%) for the Uriscreen test. Conclusion: All 4 point-of-care tests were suboptimal for use in the broad range of children presenting with acute illnesses to general practice. General practitioners need novel methods for obtaining reliable urine samples during the time of the consultation, especially for children not yet toilet-trained.
Chapter
Contrast-enhanced voiding urosonography (ceVUS) has been used to detect and grade vesicoureteral reflux for the past three decades. Following recent regulatory agency approval of an ultrasound contrast agent for this indication, it is performed more routinely worldwide. The ceVUS technique and reflux grading are comparable to voiding cystourethrography (VCUG). Many authors have shown ceVUS to be as good as if not superior to VCUG and radionuclide cystography for reflux detection and grading. The urethra and urethral pathology are also readily depicted. This chapter describes the current practice as well as advanced techniques of ceVUS.
Article
Objectives: The association of noninfectious diarrhea with extraintestinal infections such as otitis media, pneumonia, or febrile urinary tract infections (UTIs) is commonly known as parenteral diarrhea. Although this association has been described for over a century and parenteral diarrhea is mentioned in current reference literature, available evidence for this association seems to be limited. The primary research question was to determine if there is an association between UTIs and reports of diarrhea. Methods: A retrospective chart review was performed using the medical records from October 1, 2017, to March 29, 2019 at our tertiary pediatric medical center. We searched for all cases of afebrile and febrile UTIs evaluated in the pediatric emergency department or admitted directly to the hospital for treatment. All children younger than 5 years were eligible for inclusion. Exclusion criteria included children with recent urological procedures, known urinary tract disease, immune suppression, sepsis, or known gastrointestinal diseases. The medical records of each of the pediatric patients with culture-positive UTIs were reviewed for reports of concurrent diarrhea or diarrhea-like illness. In addition, using a comparative quantitative design, we performed a retrospective chart review of all children younger than 5 years with 1 of 2 noninfectious chief complaints, head trauma, and extremity fractures, presenting during the same period to assess the background rate of reported diarrhea.This research project received the approval of the University of South Alabama's Institutional Review Board. Results: A total of 236 children with a culture-positive UTI presented to our pediatric medical center from October 1, 2017 to March 29, 2019. Reports of diarrhea were documented in the medical record for 44 of the 236 UTIs (18.6%). Escherichia coli was the predominant infectious agent in 32 of the 44 children (72.7%) with culture-positive UTIs and diarrhea. Of the 368 comparison group patients who visited the pediatric emergency department for a noninfectious complaint, diarrhea was reported in 2 patients (0.01%). Conclusions: Our retrospective review of pediatric patients younger than 5 years with culture-proven UTIs found an association of reported diarrhea. It is our opinion based on our single-center retrospective chart review that the current available evidence suggests an association between UTIs and extraintestinal diarrhea. Future prospective studies are recommended to confirm this association.
Article
Résumé Introduction L’infection urinaire fébrile est l’infection bactérienne la plus fréquente chez l’enfant, pouvant aboutir à des complications sévères infectieuses et rénales, nécessitant un diagnostic précoce et une antibiothérapie ciblée. Notre objectif était d’étudier l’épidémiologie bactérienne locale et le profil de résistance aux antibiotiques chez les enfants hospitalisés pour infection urinaire fébrile dans deux centres pédiatriques du grand-est. Patients et méthodes L’étude incluait les enfants admis aux urgences pédiatriques du Centre hospitalier universitaire de Strasbourg et du Centre hospitalier de Saverne pour infection urinaire fébrile de janvier 2019 à décembre 2020. Les bactéries isolées et le profil de résistance étaient étudiés à partir des examens cytobactériologiques des urines. Résultats Nous avons analysé 214 examens cytobactériologiques des urines réalisés chez 208 patients. Les bactéries principalement retrouvées étaient Escherichia coli (82 %), dont bêtalactamase de spectre étendu (2,8 %), Enterococcus faecalis (7 %), Klebsiella spp (5 %) et Proteus mirabilis (2 %). L’E. coli était résistant dans respectivement 43, 33 et 14 % des cas à l’amoxicilline, l’amoxicilline/acide clavulanique et au cotrimoxazole, et sensible au céfixime et ceftriaxone dans 99 % des cas. Une céphalosporine de 3e génération (C3G) était utilisée en intraveineux dans 98 % des cas en traitement probabiliste. Moins de 2 % des patients eurent un traitement per os par céfixime dès l’initiation de l’antibiothérapie. Conclusion Nous avons documenté le spectre des uropathogènes et le profil de résistance de l’E. coli dans les infections urinaires fébriles pédiatriques prises en charge dans 2 centres. Un protocole local d’antibiothérapie probabiliste basé sur nos résultats a été rédigé en accord avec les recommandations nationales.
Article
Background: Few studies have evaluated the efficacy of ultrasonography (US) and abdominal radiography in assessing bladder and bowel dysfunction in children aged <24 months. We aimed to investigate the association between the risk of urinary tract infection (UTI) recurrence and fecal impaction using imaging findings. Methods: The medical records of 121 children (aged <24 months) with initial febrile UTI (fUTI) who were admitted to the authors' institution from January 2004 to September 2019 were reviewed retrospectively. We evaluated the rectal diameters of children with suspected fecal impaction that were measured using transabdominal US, or the rectal diameters divided by the distance between the ischial spines that were measured using abdominal radiography. Based on previous reports, we defined fecal impaction as a transabdominal US score of >30 mm or an abdominal radiography score of >0.5. The definition of functional constipation was based on the child/adolescent Rome IV criteria - i.e., a maximum stool frequency of twice per week. Results: The median age at initial fUTI diagnosis was 4 months. The occurrence of fecal impaction identified via imaging was significantly greater in patients with UTI recurrence than in those without recurrence: yes/no: 17/9 (65.4%) versus 35/60 (36.8%); P = 0.013. On the other hand, the occurrence rates of constipation based on stool frequency did not differ between the two groups. In multiple logistic analyses, fecal impaction detected via imaging was identified as an independent risk factor for fUTI recurrence. Conclusions: Fecal impaction observed via US and abdominal radiography may be useful in predicting the recurrence of fUTI in children.
Article
Objective To perform an exploratory, descriptive pilot study of the systemic and local immune environment in patients with vesicoureteral reflux (VUR) and bladder-bowel dysfunction (BBD). Methods Consecutive children with VUR undergoing intravesical ureteral reimplantation were enrolled. Patients were assessed for presence of BBD by reported patient history and validated questionnaire. Fresh blood and bladder tissue, collected at the time of surgery, were immediately processed for analysis. Immune cell compositions were determined via flow cytometry. Immune cell activation was also defined at the time of analysis. LegendPlex assay analysis was utilized to define levels of circulating chemokines and cytokines. Results A total of 7 patients were enrolled. Although percentages of circulating immune cells in the blood of those with VUR/BBD and VUR alone were similar, within bladder tissue, VUR/BBD demonstrated increased immune infiltrates compared to VUR alone. Bladder sample analysis showed that B cells, and Effector Memory and Naïve T cell percentages were significantly increased in VUR/BBD patients compared to VUR patients. T cell expression of PD1 was increased in bladder tissues of BBD/VUR. Additionally, analysis of circulating neutrophils displayed significantly increased upregulation of PDL-1 in patients with VUR/BBD vs those with VUR only. Conclusion These pilot data suggest an immune-rich microenvironment is present within VUR. Severity of inflammation appeared to correlate with presence of BBD. This implies that targeting pelvic inflammation may be a novel therapy for children with VUR- or non-VUR-related BBD. Follow-up studies are currently underway.
Article
Background There are scarce reports about the association of Klebsiella oxytoca ( K. oxytoca ) with urinary tract infection (UTI) in children. We aimed to evaluate the prevalence of fimA, mrkA, matB and pilQ adhesins genes and extended-spectrum beta-lactamase (ESBL) genes blaCTX-M, blaTEM and blaSHV by polymerase chain reaction (PCR) and to study biofilm formation and antibiotics resistance in K. oxytoca from children with UTI. Methods This study was a retrospective cross-sectional study that included 120 children with UTI due to K. oxytoca . The bacteria were subjected to molecular detection of fimA, mrkA, matB and pilQ adhesins genes and ESBL genes blaCTX-M, blaTEM and blaSHV by PCR. Biofilm capacity was determined by the microtiter plate method. Results The isolated K. oxytoca had positive ESBL activity in 45.8% of isolates. About 40% of isolates were biofilm producers. The frequency of adhesion genes among K. oxytoca was 91.7%, 83.3%, 48.3% and 37.5% for matB, pilQ, fimA and mrkA genes, respectively. For ESBL genes, the frequency was 38.3%, 36.7% and 33.3% for blaCTX-M, blaSHV and blaTEM genes, respectively. The commonest genes among ESBL isolates were blaCTX-M (83.6%), blaSHV (80%) then blaTEM gene (72.7%). A significant association (p=0.048) was detected between ESBL activity and biofilm formation by K. oxytoca. Conclusion Present study highlights the emergence of K. oxytoca as a pathogen associated with UTI in children. There was a high prevalence of adhesin genes and ESBL genes among these isolates. The capacity of K. oxytoca to form biofilm was associated with ESBL production.
Article
Objective To examine the association between uropathogens and pyuria in children less than 24 months of age. Study design A retrospective study of children <24 months of age evaluated in the emergency department for suspected UTI with paired urinalysis (UA) and urine culture during a 6-year period. Bagged urine specimens or urine culture growing mixed/multiple urogenital organisms were excluded. Analysis was limited to children with positive urine culture as defined by the American Academy of Pediatrics clinical practice guideline culture thresholds. Results Of 30,462 children, 1,916 had microscopic UA and positive urine culture. Urine was obtained by transurethral in-and-out catheterization in 98.3% of cases. Pyuria (≥5 WBCs per high-powered field) and positive leukocyte esterase (small or more) on the urine dipstick were present in 1,690 (88.2%) and 1,692 (88.3%) of the children respectively. Children with non-E. coli species were less likely to exhibit microscopic pyuria than children with E. coli (OR 0.24, 95% CI 0.17-0.34) with more pronounced effect on Enterococcus and Klebsiella (OR 0.08, 95% CI 0.03-0.18, and OR 0.18, 95% CI 0.11-0.27 respectively). Similarly, positive leukocyte esterase was less frequently seen in non-E. coli uropathogens compared with E. coli. Conclusion Pyuria and leukocyte esterase are not sensitive markers to identify non-E. coli UTI in young children. More sensitive screening biomarkers are needed to identify UTI with these uropathogens.
Article
Background Positioning the Instillation of Contrast cystography (PICc) is used to identify occult vesicoureteric reflux (VUR) in patients with recurrent urinary tract infections (UTI) despite optimized bladder and bowel function and without VUR demonstrated on conventional imaging. Aim To determine the incidence of finding occult VUR in such patients usingPICc and the benefit, if any, of treating it. We also assessed if this was influenced by abnormalities on the pre-operative DMSA. Patients and methods This was a retrospective review of PICc in our hospital between 2016 and 2018 and involved three paediatric urologists. The primary indication for PICc was two or more culture proven UTIs despite optimized bladder and bowel function and no reflux on voiding cystourethrography (VCUG) or indirect radionuclide cystography (I-RNC). All children had a preoperative DMSA scan to document any abnormalities. PICc was performed in a standardized way to each ureteric orifice. If occult reflux was found, it was treated concomitantly by cystoscopic injection of Deflux®. To assess the influence of the pre-operative DMSA status, the cohort was subdivided into two groups based on the DMSA scan: Group 1-abnormal DMSA, Group 2-normal DMSA. The median follow-up was 26 months (range 3–39 months). Results PICc was performed in 25 patients [23 females and 2 males; median age: 7 years (range 2–16 years; IQR = 4)]; 17 from Group 1 and 8 from Group 2. Occult VUR was identified in 22 patients (88%); 15/17 (88.2%) in Group 1 and 7/8 (87.5%) in Group 2 (p = 0.9). After cystoscopic treatment, 21/25 (84%) became infection free and this was not influenced by the preoperative DMSA status (p = 0.6). Fig 1. Discussion In this challenging group of patients, looking for and treating occult reflux appears to be clinically useful and beneficial. The ability to test and treat at the same sitting is an added advantage of PICc. The DMSA results did not influence the diagnostic or therapeutic aspect of the process. Our results concur with other published literature. Conclusion There is a high incidence of finding occult reflux using PICc in this cohort of patients. Concomitant cystoscopic treatment led to 84% of children becoming infection free on follow up. Abnormalities on DMSA did not influence either the likelihood of finding occult reflux or the likelihood of successful treatment. • Download : Download high-res image (234KB) • Download : Download full-size image Summary fig..
Article
Background The sensitivity and specificity of the leukocyte esterase test are relatively low for a screening test for urinary tract infection (UTI). More accurate tests could reduce both overtreatment and missed cases. This study aimed to determine whether neutrophil gelatinase-associated lipocalin (NGAL) can replace leukocyte esterase in the diagnosis of UTI and/or whether NGAL accurately identifies children with acute pyelonephritis.Methods Data sources—MEDLINE and EMBASE. We only considered published studies that evaluated the results of an index test (NGAL) against the results of urine culture (for UTI) or against the results of dimercaptosuccinic acid (for acute pyelonephritis) in children aged 0 to 18 years. Two authors independently applied the selection criteria to all citations and independently extracted the data.ResultsA total of 12 studies met our inclusion criteria. Four studies (920 children) included data on NGAL for UTI; eight studies (580 children) included data on NGAL for pyelonephritis. We did not pool accuracy values because the included studies used different cutoff values. For the diagnosis of UTI, urinary NGAL appeared to have better accuracy than the leukocyte esterase test in all included studies. For the diagnosis of pyelonephritis, neither plasma NGAL nor urinary NGAL had high sensitivity and/or specificity. The number of studies was the main limitation of this systematic review.Conclusions Urinary NGAL appears promising for the diagnosis of UTI; however, larger studies are needed to validate this marker as a replacement for leukocyte esterase. The use of NGAL for diagnosing acute pyelonephritis requires further study.
Article
Purpose of review: Vesicoureteral reflux (VUR) management has been steadily evolving over the last several years. There is not a definitive algorithm for operative intervention, but there are some recognized patterns to follow when caring for this patient base. It is extremely relevant to review the rationale behind practice patterns as both literature and clinical practice are dynamic. Recent findings: VUR is a common malady that is emotionally, physically, and financially draining for families. As new treatment options emerge with minimally invasive techniques and older methods are re-explored, it is imperative to re-evaluate care strategies. This article reviews the mainstays of treatment in addition to newer therapeutic modalities. Summary: The decision to operate on any patient, particularly pediatric patients, must be preceded by sound clinical judgment. Thoughtful planning must be utilized to ensure every patient receives individualized and up-to-date VUR management. This article reviews indications for surgical intervention to consider when managing these patients.
Article
Background. In recent studies, renal ultrasonography and dimercapto-succinic acid (DMSA) scan have a role in predicting vesicoureteral reflux in children with febrile urinary tract infection (UTI). Materials and Methods. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), and negative likelihood ratio (NLR) were defined for ultrasonography and DMSA scan to predict vesicoureteral reflux in 70 children with febrile UTI. Results. Renal ultrasonography sensitivity, specificity, PPV, NPV, PLR, and NLR for vesicourethral reflux prediction was 0.57, 0, 1, 0, 0.57, and 0.47 and sensitivity, specificity, PPV, NPV, PLR, and NLR of DMSA scan for predicting vesicourethral reflux was 0.75, 0.9, 0.33, 0.98, 7.5, and 0.27, respectively. Conclusions. Ultrasonography cannot predict the presence of VUR, but DMSA scan has a good sensitivity in this context. Therefore, by observation of DMSA scan results, it can be decided whether to perform VCUG or not.
Article
Objective To identify risk factors for febrile recurrence of urinary tract infections (UTIs) in children with a history of UTI. Study design We included 500 children 2 to 72 months of age with a history of UTI who were followed prospectively for approximately 2 years in the context of two previously conducted studies (RIVUR and CUTIE). We identified significant risk factors for febrile recurrences among children not receiving antimicrobial prophylaxis using univariate and multivariate logistic regression. Result On univariate analysis, non-Black race, febrile index UTI, bowel-bladder dysfunction, grade IV vesicoureteral reflux, renal scarring at baseline, and renal-bladder ultrasound abnormalities were associated with febrile recurrence. On multivariate analysis, the following variables independently increased the odds of febrile recurrences (odds ratio; 95% confidence interval): non-Black race (7.1; 1.5-127.9), bowel-bladder dysfunction (2.6; 1.1-5.3), febrile index UTI (2.5; 1.1-6.9), abnormalities on renal-bladder ultrasound (2.6; 1.2-5.6), grade IV vesicoureteral reflux (3.9; 1.4-10.5), and renal scarring at baseline (4.7; 1.2-19.1). Conclusions Non-Black race and grade IV vesicoureteral reflux increased the odds of febrile recurrence of UTI. Although our findings should stimulate other studies to further explore the relationship between race and UTIs, given that the link between race and UTI recurrence is unclear, race should not be used to make decisions regarding management of children with a UTI.
Article
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Concordance between conventional culture and 16S rRNA gene amplicon sequencing appears to be high. In children with equivocal culture results, 16S rRNA gene results may provide information that may help clarify the diagnosis.
Chapter
This chapter describes the physiology and selected disorders related to urinary tract, kidneys, blood pressure, fluids, and electrolytes.
Article
Objective To evaluate increased kidney echogenicity as a predictor of vesicoureteral reflux (VUR) in young children with first febrile urinary tract infection (UTI). Study design We performed a single center retrospective study of hospitalized children with first febrile UTI diagnosed in accordance with the American Academy of Pediatrics guidelines. All patients had kidney bladder ultrasound (KBUS) and voiding cystourethrography (VCUG). Variables analyzed using Chi-square test or Mann-Whitney U test as appropriate. Multivariable logistic regression analysis was performed for the abnormal KBUS findings and odds ratio (OR) and 95% confidence Interval (95%CI) were calculated. Results Our cohort included 415 children (830 kidney units) with median age of 5 months (one month to 5 years) and 80% were females. 132 (31.8%) patients had abnormal KBUS, including increased echogenicity in 45 patients. Overall, 42.2% of patients with increased echogenicity had VUR versus 23.3% with normal ultrasound (P=0.013) and 31.1% of patients with increased echogenicity had high-grade III-V VUR versus 8.1% with normal ultrasound (P=0.001). In total, 24.3% of kidneys with increased echogenicity had VUR versus 20% with normal ultrasound (P=0.246) and 20% of kidneys with increased echogenicity had high-grade III-V VUR versus 9.9%with normal ultrasound (P=0.005). Conclusion These data support adding increased kidney echogenicity to the list of other KBUS findings that are helpful in decision making about a need for VCUG in young children with first febrile UTI.
Chapter
Numerous conditions can potentially affect the urinary tract. Imaging techniques are key diagnostic tools that allow the evaluation of anatomical and functional abnormalities of some of them. In some cases, the most appropriate management is dictated by the results of such diagnostic tools. It is important that the clinician knows the role of the imaging techniques that are widely available in order to provide the best evaluation of patients. The objective of this review is to describe the role of different imaging techniques in prevalent conditions of the urinary tract and to describe different interventional diversion alternatives.
Article
Objectives Oral treatment of febrile urinary tract infections (FUTIs) can be impaired by MDR Enterobacterales often combining ESBL and inhibitor-resistant genes. We studied the impact of β-lactamases and Enterobacterales’ genotypes on the cefixime, cefpodoxime and mecillinam ± amoxicillin/clavulanate MICs. Materials and methods In this multicentric study, we included 251 previously whole-genome-sequenced ESBL-producing Enterobacterales, isolated in French children with FUTIs. The MICs of cefixime, cefpodoxime, mecillinam alone and combined with amoxicillin/clavulanate were determined and analysed with respect to genomic data. We focused especially on the isolates’ ST and their type of β-lactamases. Clinical outcomes of patients who received cefixime + amoxicillin/clavulanate were also analysed. Results All isolates were cefixime and cefpodoxime resistant. Disparities depending on blaCTX-M variants were observed for cefixime. The addition of amoxicillin/clavulanate restored susceptibility for cefixime and cefpodoxime in 97.2% (MIC50/90 of 0.38/0.75 mg/L) and 55.4% (MIC50/90 of 1/2 mg/L) of isolates, respectively, whatever the ST, the blaCTX-M variants or the association with inhibitor-resistant β-lactamases (34.2%). All isolates were susceptible to mecillinam + amoxicillin/clavulanate with MIC50/90 of 0.19/0.25 mg/L, respectively. Neither therapeutic failure nor any subsequent positive control urine culture were reported for patients who received cefixime + amoxicillin/clavulanate as an oral relay therapy (n = 54). Conclusions Despite the frequent association of ESBL genes with inhibitor-resistant β-lactamases, the cefixime + amoxicillin/clavulanate MICs remain low. The in vivo efficacy of this combination was satisfying even when first-line treatment was ineffective. Considering the MIC distributions and pharmacokinetic parameters, mecillinam + amoxicillin/clavulanate should also be an alternative to consider when treating FUTIs in children.
Article
Objectives: Reflux nephropathy is a radiologic condition commonly used to express the existence of renal morphological lesions in patients who have or had vesicoureteral reflux (VUR). This morphological concept is used based on the image data collected, without conducting basic complementary renal function studies. The present study was designed to demonstrate that patients with active VUR present different functional renal alterations from those shown by patients with disappeared VUR. Patients and methods: Longitudinal descriptive retrospective analysis including 89 children (46M, 43F) with VUR diagnosis through a standard voiding cystourethrogram (VCUG). The basic renal function tests collected were the maximum urinary osmolality (UOsm) and the urinary albumin/creatinine and NAG/creatinine ratios. The data collected corresponded to two moments, when VUR was diagnosed and when it had already disappeared. Results: Quantitative differences were verified in the three functional parameters when comparing those corresponding to both moments of the study. In the qualitative analysis, in relation to the intensity of the VUR, differences were observed in UOsm at diagnosis and in the albumin/creatinine ratio once the VUR had cured. At this last moment, a significant increase in the albumin/creatinine ratio was observed in patients with loss of renal parenchyma in relation to those without residual morphological lesions. Conclusions: Concentrating ability defect is the most frequent finding in children with active reflux (true reflux nephropathy), whereas the most frequent functional disturbance found, once VUR has cured, is an increase in urinary albumin excretion, related to parenchymal damage. The term dysplastic-scarring nephropathy, could be more appropriate for patients with residual morphological lesions and impaired renal function, once VUR is cured.
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Background: Tc99m DMSA (dimercaptosuccinic acid) scintigraphy has a high sensitivity for the detection of cortical kidney damage. Aim: To evaluate the Tc99m DMSA renal scintigraphy in children with a first episode of acute pyelonephritis and its association with laboratory parameters, kidney ultrasound and vesicoureteral reflux. Patients and methods: We studied 143 children (age range 8 days, 12 Years, 66% female) hospitalized with the clinical diagnosis of acute pyelonephritis (first episode) with a positive urine culture and a renal scintigraphy performed within seven days of diagnosis. DMSA was considered the gold standard for the detection of cortical lesions. Its results were related to the presence of fever C-reactive protein (CRP), erythrocyte sedimentation rate white blood count (WBC), ultrasound examination and vesicoureteral reflux. Results: Seventy nine percent of the population bad an abnormal DMSA scan. There were no differences between sex, age and laboratory parameters in children with normal or abnormal DMSA scans, except for CRP (p < 0.005). Ultrasound was coincident with the scan in 32% of patients. Eighteen percent bad vesicoureteral reflux. Conclusions: There is a high proportion of abnormal DMSA scans in children with a first episode of acute pyelonephritis.
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Febrile urinary tract infections are common in children and associated with the risk for renal scarring and long-term complications. Antimicrobial prophylaxis has been used to reduce the risk for recurrence. We performed a study to determine whether no prophylaxis is similar to antimicrobial prophylaxis for 12 months in reducing the recurrence of febrile urinary tract infections in children after a first febrile urinary tract infection. The study was a controlled, randomized, open-label, 2-armed, noninferiority trial comparing no prophylaxis with prophylaxis (co-trimoxazole 15 mg/kg per day or co-amoxiclav 15 mg/kg per day) for 12 months. A total of 338 children who were aged 2 months to <7 years and had a first episode of febrile urinary tract infection were enrolled: 309 with a confirmed pyelonephritis on a technetium 99m dimercaptosuccinic acid scan with or without reflux and 27 with a clinical pyelonephritis and reflux. The primary end point was recurrence rate of febrile urinary tract infections during 12 months. Secondary end point was the rate of renal scarring produced by recurrent urinary tract infections on technetium 99m dimercaptosuccinic acid scan after 12 months. Intention-to-treat analysis showed no significant differences in the primary outcome between no prophylaxis and prophylaxis: 12 (9.45%) of 127 vs 15 (7.11%) of 211. In the subgroup of children with reflux, the recurrence of febrile urinary tract infections was 9 (19.6%) of 46 on no prophylaxis and 10 (12.1%) of 82 on prophylaxis. No significant difference was found in the secondary outcome: 2 (1.9%) of 108 on no prophylaxis versus 2 (1.1%) of 187 on prophylaxis. Bivariate analysis and Cox proportional hazard model showed that grade III reflux was a risk factor for recurrent febrile urinary tract infections. Whereas increasing age was protective, use of no prophylaxis was not a risk factor. For children with or without primary nonsevere reflux, prophylaxis does not reduce the rate of recurrent febrile urinary tract infections after the first episode.
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The standard recommendation for treatment of young, febrile children with urinary tract infection has been hospitalization for intravenous antimicrobials. The availability of potent, oral, third-generation cephalosporins as well as interest in cost containment and avoidance of nosocomial risks prompted evaluation of the safety and efficacy of outpatient therapy. In a multicenter, randomized clinical trial, we evaluated the efficacy of oral versus initial intravenous therapy in 306 children 1 to 24 months old with fever and urinary tract infection, in terms of short-term clinical outcomes (sterilization of the urine and defervescence) and long-term morbidity (incidence of reinfection and incidence and extent of renal scarring documented at 6 months by 99mTc-dimercaptosuccinic acid renal scans). Children received either oral cefixime for 14 days (double dose on day 1) or initial intravenous cefotaxime for 3 days followed by oral cefixime for 11 days. Treatment groups were comparable regarding demographic, clinical, and laboratory characteristics. Bacteremia was present in 3.4% of children treated orally and 5.3% of children treated intravenously. Of the short-term outcomes, 1) repeat urine cultures were sterile within 24 hours in all children, and 2) mean time to defervescence was 25 and 24 hours for children treated orally and intravenously, respectively. Of the long-term outcomes, 1) symptomatic reinfections occurred in 4.6% of children treated orally and 7.2% of children treated intravenously, 2) renal scarring at 6 months was noted in 9.8% children treated orally versus 7.2% of children treated intravenously, and 3) mean extent of scarring was approximately 8% in both treatment groups. Mean costs were at least twofold higher for children treated intravenously ($3577 vs $1473) compared with those treated orally. Oral cefixime can be recommended as a safe and effective treatment for children with fever and urinary tract infection. Use of cefixime will result in substantial reductions of health care expenditures.
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Children with urinary tract infections (UTI) are at risk of renal scarring which may lead to impaired renal function and hypertension. This study examines the risk factors that predispose to recurrent UTI in children and the role of recurrent UTI in renal scarring. A group of 290 children under 5 years of age with a first symptomatic UTI were studied. Micturating cystourethrogram and dimercaptosuccinic acid (DMSA) renal scintigraphy were performed at entry, and DMSA was repeated 1 year later. Two hundred and sixty-one children (90%) were followed up at 1 year. There were 46 confirmed recurrent infections in 34 children, a recurrence rate of 12%. Multiple recurrence occurred in 14/34 (34%) children. Age of less than 6 months on entry independently predicted for recurrent UTI (odds ratio (OR): 2.9)). Compliance with prophylactic antibiotics fell throughout the year of follow up. Vesicoureteric reflux (VUR) was present in 14/34 (34%) of the group with recurrent UTI, 69/256 (27%) without recurrence. Urinary tract infection was significantly associated with bilateral and intrarenal reflux; grade 3-5 reflux independently predicted for recurrent UTI (OR: 3.5). Recurrent UTI was significantly associated with high grade DMSA defects on entry, renal parenchymal defects at 1 year follow up, and new defects at 1 year. The independent risk factors for recurrent UTI identified by this study were an age of less than 6 months at the index UTI and grade 3-5 VUR. These findings suggest more selective targeting may minimize problems associated with prophylaxis and improve outcomes for children with urine infection.
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Experimental evidence suggests that neutrophils and their metabolites play an important role in the pathogenesis of pyelonephritis. The aim of this study was to investigate the diagnostic value of polymorphonuclear elastase-a(1)-antitrypsin complex (E-a(1)-Pi) for the detection of acute pyelonephritis in children. Eighty-three patients, 29 boys and 54 girls, 25 days to 14 years of age, with first-time symptomatic urinary tract infection were prospectively studied. Fifty-seven healthy children served as controls. Dimercaptosuccinic acid (DMSA) scan and voiding cystourethrography were performed in all patients. Plasma and urinary E-a(1)-Pi, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), neutrophil count, urinary N-acetyl-beta-glucosaminidase (NAG), N-acetyl-beta-glucosaminidase b (NAG b), and creatinine levels were measured in all patients on admission and 3 days after the introduction of antibiotics. The same markers were also measured in the control subjects. Planar DMSA scintigraphy demonstrated changes of acute pyelonephritis in 30 of 83 children (group A). It was normal in the remaining 53 children (group B). The sex and age distributions were not significantly different between the 2 groups, as well as between the patients and the control subjects (group C). Nineteen of the 53 children with a normal DMSA had body temperature >/=38 degrees C, whereas all but 4 children with abnormal DMSA had temperature >/=38 degrees C. Therefore, the temperature was significantly different between these 2 groups. The sensitivity and specificity of fever (>/=38 degrees C) as an indicator of renal involvement based on isotopic findings were 86% and 64%, respectively. Given the significant number of the febrile children with normal DMSA scintiscans, group B was subdivided into B(1) with 19 febrile children (14 boys and 5 girls) and B(2) with 34 children whose body temperature was below 38 degrees C (8 boys and 26 girls). The sex and age distribution was significantly different between groups B(1) and B(2). The mean age of group B(1) was.78 years (range: 28 days to 9 years; median:.25 years; standard deviation: 2.1). All but 1 child in this group were younger than 1 year of age. In contrast, in group B(2), there were only 4 infants, the remaining 30 children were older than 2.5 years (mean age: 6 years; median: 7 years; standard deviation: 3.5; range: 34 days to 12 years). The mean duration of fever before hospital admission was 2.8 days for group A and 1.8 days for group B(1). This difference was not statistically significant. Similarly, body temperature was not significantly different between these 2 groups. The distribution of plasma E-a(1)-Pi values was normal in the control subjects. The sensitivity and specificity of plasma E-a(1)-Pi, as an indicator of renal involvement, were 96% and 50%, respectively, taking the 95th percentile of the reference range as a cutoff value. However, considering as a cutoff value the level of 72 microg/dL (95th percentile of group B(2)), its sensitivity and specificity were 74% and 86%, respectively. Plasma E-a(1)-Pi levels were significantly elevated in group A compared with group B and in both groups, the plasma E-a(1)-Pi values were significantly higher than in the control subjects. A significant difference also was noticed between group A and each of the subgroups B(1) and B(2) and also between the subgroups themselves. Plasma E-a(1)-Pi concentrations correlated significantly with neutrophil count in groups A (r =.3), B (r =.4), and B(2) (r =.46), but the correlation was not significant in group B(1.) ESR levels showed, among the different groups, similar differences with those of E-a(1)-Pi values. Unlike E-a(1)-Pi, CRP levels were comparable between groups A and B(1), which both consisted of febrile children. Neutrophil count was not significantly different between subgroups B(1) and B(2). (ABSTRACT TRUNCATED)
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To determine the incidence of renal scars in children with primary vesicoureteral reflux taking into consideration the following variables: sex, age at diagnosis, febrile urinary infection, degree of reflux and bacteria specimen. Retrospective study of 58 children with age ranging from 2 months to 11 years, presenting primary vesicoureteral reflux detected by voiding cystourethrogram after documented episode of urinary tract infection. The diagnosis of renal scarring was obtained by dimercaptosuccinic acid scan 5 months after the treatment of the urinary infection; in 40 children the dimercaptosuccinic acid scan was performed again from 6 months up to 6 years after the treatment. 45 children (77.6%) were girls and 13 (22.4%) were boys, 51.7% were 2 years old or younger. The incidence of renal scarring was 55.2%. There was significant higher proportion of renal scars in girls, when the patients presented fever and dilated vesicoureteral reflux (III, IV, V). Fever and female sex were risk factors for the development of renal scars (fever--ODDS ratio=6.19 and female sex--ODDS ratio=4.12). There was a prevalence of renal scars in children over 2 years old. The interval between the beginning of the symptoms and the first medical visit was longer in the children with renal scars. New renal scars were observed in 12.5%. Fever and female sex were risk factors for the presence of renal scars, mainly in the dilated vesicoureteral reflux. The high incidence of renal scars in this study may be related to delayed diagnosis of vesicoureteral reflux.
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To provide valid assessments of answers to prognostic questions, systematic reviews must appraise the quality of the available evidence. However, no standard quality assessment method is currently available. To appraise how authors assess the quality of individual studies in systematic reviews about prognosis and to propose recommendations for these quality assessments. English-language publications listed in MEDLINE from 1966 to October 2005 and review of cited references. 163 systematic reviews about prognosis that included assessments of the quality of studies. A total of 882 distinct quality items were extracted from the assessments that were reported in the various reviews. Using an iterative process, 2 independent reviewers grouped the items into 25 domains. The authors then specifically identified domains necessary to assess potential biases of studies and evaluated how often those domains had been addressed in each review. Fourteen of the domains addressed 6 sources of bias related to study participation, study attrition, measurement of prognostic factors, measurement of and controlling for confounding variables, measurement of outcomes, and analysis approaches. Reviews assessed a median of 2 of the 6 potential biases; only 2 (1%) included criteria aimed at appraising all potential sources of bias. Few reviews adequately assessed the impact of confounding (12%), although more than half (59%) appraised the methods used to measure the prognostic factors of interest. Reviews may have been missed by the search or misclassified because of incomplete reporting. Validity and reliability testing of the authors' recommendations are required. Quality appraisal, a necessary step in systematic reviews, is incomplete in most reviews of prognosis studies. Adequate quality assessment should include judgments about 6 areas of potential study biases. Authors should incorporate these quality assessments into their synthesis of evidence about prognosis.
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Renal scintigraphy, generally using 99mTc-DMSA, is the accepted reference standard for detection of renal cortical changes. The timing of the test, i.e., whether an acute 99mTc-DMSA scan, a follow-up only or both scans should be performed, however, remains open to discussion. In our study, a six-month follow- up DMSA scan was performed in all the children diagnosed with a first attack of acute pyelonephritis (APN) in two large paediatric clinics of Charles University's 3rd School of Medicine in Prague during a five-year period. All diagnoses were confirmed by a paediatric nephrologist. 382 children (267 girls, 115 boys) aged between 7 months and 19 years were included in the study. For analytical purposes, the patients were divided into 4 age groups: I--less than 1 year of age, II--1-5 years, III--5-10 years, and IV--10-19 years. In all children younger than five years, a micturition cystourethrogram (MCUG) for detection of vesicoureteric reflux (VUR) was performed between one and three months after the APN episode. Static renal scintigraphy, using an HR collimator with parallel holes was performed using a planar Gamma camera MB 9200 (Gamma Budapest) in all children six months after APN, with a complement of pinhole images, SPECT or PSPECT of the kidneys. 1. In group I, all four children with positive VUR on MCUG had a pathological DMSA scan, while only two of the 32 patients with negative VUR had a pathological DMSA. 2. In group II, 17 children had VUR on MCUG, six of them with a pathological and 11 with a normal DMSA scan. Most of the 221 children without VUR had a normal DMSA scintigraphy; pathological findings were present in 17 children only. 3. In group III, all children with VUR, but only 5 out of 53 without VUR, had a pathological DMSA scan. 4. Five out of 50 children in group IV had a pathological DMSA. APN occurred most frequently in group II (62.3%, or 238 children) and ranged between 10-15% in the remaining groups. APN was found very frequently in boys less than one year old and showed a marked decrease with increasing age. Among girls, however, APN incidence was observed to increase with age. Pathological renal changes were present in children with, as well as without, VUR. The incidence of pathological DMSA findings six months after APN was relatively low (44/382 patients, or 11.5%). Regular monitoring of these children is very important for detection of renal scarring.
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To compare the efficacy of oral antibiotic treatment alone with treatment started parenterally and completed orally in children with a first episode of acute pyelonephritis. Multicentre, randomised controlled, open labelled, parallel group, non-inferiority trial. 28 paediatric units in north east Italy. 502 children aged 1 month to <7 years with clinical pyelonephritis. Oral co-amoxiclav (50 mg/kg/day in three doses for 10 days) or parenteral ceftriaxone (50 mg/kg/day in a single parenteral dose) for three days, followed by oral co-amoxiclav (50 mg/kg/day in three divided doses for seven days). Main outcomes measures Primary outcome was the rate of renal scarring. Secondary measures of efficacy were time to defervescence (<37 degrees C), reduction in inflammatory indices, and percentage with sterile urine after 72 hours. An exploratory subgroup analysis was conducted in the children in whom pyelonephritis was confirmed by dimercaptosuccinic acid (DMSA) scintigraphy within 10 days after study entry. Intention to treat analysis showed no significant differences between oral (n=244) and parenteral (n=258) treatment, both in the primary outcome (scarring scintigraphy at 12 months 27/197 (13.7%) v 36/203 (17.7%), difference in risk -4%, 95% confidence interval -11.1% to 3.1%) and secondary outcomes (time to defervescence 36.9 hours (SD 19.7) v 34.3 hours (SD 20), mean difference 2.6 (-0.9 to 6.0); white cell count 9.8x10(9)/l (SD 3.5) v 9.5x10(9)/l (SD 3.1), mean difference 0.3 (-0.3 to 0.9); percentage with sterile urine 185/186 v 203/204, risk difference -0.05% (-1.5% to 1.4%)). Similar results were found in the subgroup of 278 children with confirmed acute pyelonephritis on scintigraphy at study entry. Treatment with oral antibiotics is as effective as parenteral then oral treatment in the management of the first episode of clinical pyelonephritis in children. Clinical Trials NCT00161330 [ClinicalTrials.gov].
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The value of (123)I-hippuran (OIH) renal sequential scintigraphy (RSS) in predicting the evolution of defects detected by (99m)Tc-dimercaptosuccinic acid (DMSA) scanning during a first episode of acute pyelonephritis (APN) was assessed. Fifty-eight children with APN underwent (99m)Tc-DMSA planar scanning and (123)I-OIH RSS during acute infection and at least 5 mo later. Renal lesions found by (99m)Tc-DMSA scanning were classified according to the following (99m)Tc-DMSA grading system: 0 = normal, 1 = 1 lesion, 2 = 2 lesions, and 3 = diffuse damage with renal parenchymal subversion. Renal scarring was diagnosed whenever a renal cortical defect detected at the first (99m)Tc-DMSA examination persisted on the follow-up (99m)Tc-DMSA examination. Single-kidney clearance rate (Cl) was evaluated by a method that was previously validated at our institution and is based on time-activity curves measured on the heart and kidney areas by the region-of-interest technique. (99m)Tc-DMSA scanning showed renal damage in 76 kidneys and had negative findings for the remaining 40 kidneys (2 patients had bilaterally negative findings). (99m)Tc-DMSA scanning determined 40 kidneys to be grade 0, 49 to be grade 1, 21 to be grade 2, and 6 to be grade 3. For (99m)Tc-DMSA grades of 0-3, the corresponding Cl mean values (in mL/min/1.73 m(2) of body surface area [BSA]) were 292 +/- 33, 237 +/- 39, 210 +/- 54, and 140 +/- 53, respectively. The Spearman regression coefficient (R) demonstrated a significant correlation between (99m)Tc-DMSA grade and Cl (R = 0.69, P < 0.0001). Thirty-six of the lesions detected by staging (99m)Tc-DMSA were shown to have recovered on follow-up renal scans, whereas 40 developed scars. A significant difference in Cl was found between the 2 groups (P < 0.0002). The Cl cutoff value was determined by univariate discriminant analysis; a Cl value of 232 mL/min/1.73 m(2) of BSA discriminated best between scarred and nonscarred kidneys, with a specificity, sensitivity, positive predictive value, negative predictive value, and overall accuracy of 95%, 95%, 90%, 97%, and 95%, respectively. Cl evaluation, in the course of acute urinary tract infection, is highly valuable in predicting the fibrotic evolution of renal damage detected on acute (99m)Tc-DMSA scanning. Also, our data show close agreement between Cl and the grade determined by staging (99m)Tc-DMSA.
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PURPOSE: The objective was to assess procalcitonin (PCT) as a marker of renal involvement in children with urinary tract infections (UTI). METHODS: The study included 60 children with UTI, aged (median) 0.6 years (range, 0.1-9.5 years), admitted to a pediatric hospital. White blood cell count, C-reactive protein (CRP), and PCT levels were measured on admission and on the third treatment day, whereas renal involvement was assessed with dimercaptosuccinic acid (DMSA) scintigraphy within 7 days after admission and after 6 months. RESULTS: During febrile UTI, PCT, and CRP levels increased in parallel with the severity of renal lesions in acute DMSA. During repeat DMSA, PCT levels were increased in the group with partially versus totally reversible renal lesions (5.3 μg/L vs 3.0 μg/L; P = 0.005). Procalcitonin and CRP had increased sensitivity (94% and 100%, respectively) and negative predictive values (97% and 100%, respectively), whereas PCT had higher specificity than CRP (100% vs 55%). CONCLUSIONS: Procalcitonin is a sensitive marker of the development, severity, and persistence of renal lesions in childhood UTI. Because of the high negative predictive values of PCT, we suggest that, in case of low PCT levels, the possibility of renal involvement is low, and DMSA could be omitted.
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We investigated ethnic differences in the risk of post-pyelonephritic renal scarring in infants and children for possible genetic determinants. We searched all peer reviewed articles published from 1980 through 2006 in the PubMed(R), MEDLINE(R) (Ovid), Cochrane Central Register of Controlled Trials and EMBASE(R) databases for the keywords, "renal scarring and pyelonephritis," "renal fibrosis" and "kidney scarring." References were included only when they specified acute pyelonephritis defined by a fever, positive urine culture and areas of photopenia in the renal cortex on 99mtechnetium dimercapto-succinic acid renal scans, repeat dimercapto-succinic acid scans obtained at least 3 months after acute pyelonephritis to assess for renal cortical scar formation and absence of recurrent urinary tract infection during followup. When possible data were analyzed according to patients and renal units. Among 23 references the overall rates of renal scarring in terms of patients and renal units were 41.6% and 37.0%, respectively. In terms of patients the incidence of renal scarring following acute pyelonephritis varied by region, from 26.5% (Australia) to 49.0% (Asia). In terms of renal units the incidence of acquired renal cortical scarring varied by region, from 16.7% (Middle East) to 58.4% (Asia). When combined by vesicoureteral reflux status children and renal units with refluxing ureters exhibited an increased risk of renal scarring (odds ratios 2.8 and 3.7, respectively). Although scarring was different across some regions, only scarring in Asian studies comparing patients displayed a statistically significant difference. A regional effect explained the heterogeneity observed in the overall estimate for patients and partly for renal units. The greatest risk of renal scarring may be imparted by the presence of vesicoureteral reflux.
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Acute pyelonephritis is a common infectious disease in children and can result in permanent renal damage. Interleukin-6 (IL-6) is an important mediator of inflammation in response to bacterial infection. This study investigated the potential relationship between acute-phase IL-6 and subsequent renal scarring in children with a first time febrile acute pyelonephritis. In total, 79 children (age range 1-120 months) with a first time febrile urinary tract infection (UTI) were included. The diagnosis of acute pyelonephritis was confirmed by (99m)Tc-dimercaptosuccinic acid (DMSA) renal scan. Serum and urine samples were collected for IL-6 measurement by enzyme-linked immunosorbent assay before antibiotic treatment for the infection. The 79 children were divided into acute pyelonephritis (n=45) and lower UTI (n=34) groups according to the findings of DMSA scans. The initial serum and urine IL-6 levels of children with acute pyelonephritis were significantly higher compared with lower UTI (p < 0.001). Renal scarring was detected at the follow-up DMSA scans in 15 (34.1%) of the 44 children with acute pyelonephritis. Both serum and urine IL-6 levels during the acute phase of pyelonephritis were significantly higher in children with renal scarring than in those without (p=0.005 and p = 0.002). The median age of children with renal scarring was significantly lower than those without (p=0.034). Multiple regression analysis showed that higher initial serum and urine IL-6 levels and a younger age were associated with renal scarring. These results demonstrate that in younger children with a first time febrile acute pyelonephritis, elevations of the acute-phase serum and urine IL-6 levels were correlated with an increased risk of subsequent renal scarring.
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We assessed whether differences exist in the rates of acute photon defect and scar formation using dimercapto-succinic acid scintigraphy according to the presence and grade of vesicoureteral reflux. A total of 389 patients with a first febrile urinary tract infection were enrolled. For all patients ultrasonography, dimercapto-succinic acid scintigraphy and voiding cystourethrography were performed. Dimercapto-succinic acid scintigraphy was performed within 5 days of and 6 months after diagnosis of urinary tract infection. Voiding cystourethrography was performed after the acute phase of urinary tract infection. The rates of acute photon defect and scar formation on dimercapto-succinic acid scintigraphy according to the presence and grade of vesicoureteral reflux were assessed. A total of 125 females and 264 males were included in the study. Of the patients 93 had refluxing urinary tract infection and 296 had nonrefluxing infection. The rate of acute photon defect (74.2% vs 32.1%, p = 0.0001) and the rate of ultimate scar change on followup dimercapto-succinic acid scintigraphy were significantly higher in patients with refluxing urinary tract infection (50% vs 18.3%, p = 0.0001). Positive linear association was noted between reflux grade and acute photon defect by linear association test (p = 0.002). No association was found between reflux grade and scar formation (p = 0.262). Although vesicoureteral reflux is not a prerequisite for development of acute photon defect and subsequent renal scarring, reflux itself might be an aggravating factor for acute photon defect and scar formation. There seems to be a correlation between reflux grade and frequency of acute photon defect on dimercapto-succinic acid scintigraphy but scar change occurs independently of reflux grade.
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A prospective study examining the incidence of dimercaptosuccinic acid (DMSA) abnormalities in children at the time of acute urinary tract infection, the progression of these abnormalities following treatment and their correlation with the presence of vesicoureteral reflux is reported. DMSA scans performed within 72 hours of presentation in 65 previously healthy children with acute urinary tract infection were abnormal in 34 (52%). The scan appearances of 30 of 36 (83%) initially abnormal kidneys improved or became normal on the repeat DMSA study performed at 3 to 6 months after the acute urinary tract infection. A cystogram demonstrated significant vesicoureteral reflux in 11 of 45 cases (24%). Of these 11 cases 10 had abnormal DMSA studies and 1 had dilated upper tracts on ultrasound. Several conclusions may be drawn from our study. The incidence of DMSA abnormalities at the time of acute urinary tract infection is high but these abnormalities tend to resolve with time. An abnormal DMSA study at the time of urinary tract infection identifies most children with significant vesicoureteral reflux, and in our series a combination of ultrasound and DMSA identified all cases. This study may have major implications for the clinical investigation of children with urinary tract infection.
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This paper examines eight published reviews each reporting results from several related trials. Each review pools the results from the relevant trials in order to evaluate the efficacy of a certain treatment for a specified medical condition. These reviews lack consistent assessment of homogeneity of treatment effect before pooling. We discuss a random effects approach to combining evidence from a series of experiments comparing two treatments. This approach incorporates the heterogeneity of effects in the analysis of the overall treatment efficacy. The model can be extended to include relevant covariates which would reduce the heterogeneity and allow for more specific therapeutic recommendations. We suggest a simple noniterative procedure for characterizing the distribution of treatment effects in a series of studies.
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The relationship between urine interleukin-6 (IL-6) and interleukin-8 (IL-8)/creatinine quotients and 99mTc-dimercaptosuccinic acid (DMSA) scintigraphy, performed within 10 days of acute first-time pyelonephritis and after 1 year, was studied in 41 children. The urine IL-6 and IL-8/creatinine quotients were also related to the urine N-acetyl-beta-D-glucosaminidase (NAG) and albumin/creatinine quotients. Presence of DMSA uptake defects, reflecting local inflammation, in children in the acute phase of pyelonephritis, were associated with elevated urine IL-6/creatinine quotients (median 27 pg/mumol); in children without DMSA changes there was no increase in quotients (median non-detectable) (P < 0.05). Persistent DMSA changes at the 1-year follow-up, probably reflecting renal scarring, were only seen in children with increased urine IL-6/creatinine quotients in the acute phase (P < 0.01). No correlation was found between urine IL-8 and DMSA uptake defects. Vesicoureteral reflux (VUR) at 6-8 weeks did not correlate with the urine cytokine levels in the acute phase. The urine excretion of NAG and albumin, reflecting renal dysfunction, was associated with values of both urine IL-6 and IL-8/creatinine quotients, but not with DMSA defects or VUR. Thus, the initial urine IL-6/creatinine quotients might be used as an indicator of risk for persistent renal damage in acute pyelonephritis.
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We designed a prospective study to evaluate the ability of dimercaptosuccinic acid cortical scintigraphy and ultrasonography to detect renal parenchymal lesions in children with pyelonephritis. One hundred eleven patients 1 week to 16 years of age (median 5.5 months) with a urine culture positive for pathogens were included in the study; cortical scintigraphy and ultrasonography were repeated in 25 children after a mean follow-up of 10.5 months. Cortical scintigraphy showed renal changes in 74 children (67%), and ultrasonography showed renal changes in 39 (35%) (p < 0.001); results of the two examinations were discordant in 49 patients (kappa = 0.19). Children more than 1 year of age had a higher incidence of renal lesions than did younger children (85% vs 66%; p = 0.04). The presence of inflammatory signs (erythrocyte sedimentation rate or C-reactive protein) had an 89% sensitivity and a 25% specificity in identifying renal lesions. Among children with renal changes, vesicoureteric reflux was present in 39%. At follow-up examination, 16 children (64%) had scars. Thus we found a high incidence of renal involvement in children with pyelonephritis. We found that cortical scintigraphy is more sensitive than ultrasonography in detecting renal changes, and we believe that it should be added to the initial examination of children with suspected pyelonephritis.
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This study describes blood pressure and renal function, as well as indices of renal disease, in females with and without renal scarring followed from their first urinary tract infection (UTI) in childhood. Of the 111 patients with a median follow-up time of 15 years, 54 had renal scarring (reflux nephropathy) on urography, which was severe in 19 and moderate in 35. The glomerular filtration rate was lower in patients with severe renal scarring and correlated with renal area on urography. However, the filtration rate was decreased below the lower reference limit in only 7 patients, with a lowest value of 70 ml/min per 1.73 m2. The diastolic blood pressure was higher in women with severe scarring. Hypertension of at least 140/90 mmHg was diagnosed in 3 of 54 (5.5%) females with renal scarring, 2 before and 1 at the follow-up examination. The excretion of albumin in urine was low and not correlated to filtration rate. Tubular enzymes in urine were similar in all groups. Thus the renal function was well preserved and the incidence of hypertension low. Within this range of renal function, the level of albumin in urine did not predict the degree of renal scarring.
Article
During a 2 year period, 175 children below 6 years of age (median 0.4 year) with non-obstructive symptomatic urinary tract infection were studied by 99mTc dimercaptosuccinic acid (DMSA) scintigraphy. DMSA scintigraphy was performed at a median of 10 days after the start of treatment and was abnormal in 73 children (42%), equivocal in 29 (16%) and normal in 73 (42%). Reflux was seen in 27% of all children and in 38% of the renal units that were abnormal at DMSA scintigraphy. A decreasing frequency of abnormalities at DMSA scintigraphy was seen within the first 14 days after the start of treatment. C-reactive protein and grade of reflux correlated significantly with abnormal DMSA studies. To demonstrate renal involvement in acute urinary tract infection, DMSA scintigraphy should be performed within days after the start of treatment. It is noteworthy that reflux was seen in less than half of renal units with abnormal DMSA scintigraphy.
Article
The aim of this study was to determine whether age, C-reactive protein (CRP), body temperature, or results of voiding cystourethrography at diagnosis of first-time symptomatic urinary tract infection could predict the risk of renal damage as evaluated by dimercaptosuccinic acid (DMSA) scintigraphy performed 1 year after the infection. The study included 157 children (median age, 0.4 year, range, 5 days to 5.8 years) with first-time symptomatic urinary tract infection. In children 1 year of age or older, a body temperature of 38.5 degrees C or higher was necessary for inclusion. CRP and body temperature were measured at the time of infection, and voiding cystourethrography was performed shortly thereafter. DMSA scintigraphy was performed 1 year later in all children. After 1 year, 59 (38%) of the 157 children had renal damage as evaluated by DMSA scintigraphy, and of these, 28 (47%) had reflux. There was a positive correlation between renal damage and CRP, body temperature, and reflux. Children with high levels of CRP, high fever, and dilating reflux had a risk of renal damage up to 10 times higher than children with normal or slightly elevated CRP levels, no or mild fever, and no reflux. CRP concentration and body temperature at the index infection, in combination with the results of voiding cystourethrography, are useful in classifying children at high and low risk of scintigraphic renal damage 1 year after urinary tract infection.
Article
A prospective study was performed on 185 children with symptomatic urinary tract infection (UTI), 130F and 55M, having a median age of 0.9 y (range 0.1-9.8) at the time of UTI. The aim of the study was to find out how the 99mTechnetium-dimercaptosuccinic acid (DMSA) scan should be used to investigate UTI, and to follow the development of renal changes during pyelonephritis into subsequent permanent renal damage. All children were investigated with a DMSA scan within 5 days after admission and after 3.9-53.3 (median 9.2) weeks, and 159 were studied again after approximately 2 y (range 1.5-3.9 y). They all underwent micturition cystourethrography at the time of the second study. At the time of infection, the DMSA scan was abnormal in 85% of the children, in 58% at the first follow-up and in 36% at the second follow-up. An abnormal DMSA scan performed within 20 weeks from infection became normal in 38% of cases on the third study, while only 1/10 abnormal DMSA scans performed more than 20 weeks after infection became normal after 1.5-3.9 y. Persistent renal changes were more common in children > 4 y of age than in children < or = 1 y of age. Two months after the presenting infection, it was unusual to see a normal DMSA scan in a child with a VUR gr. > or = 3. The study suggests that DMSA changes after an index UTI may be transient for a longer period of time than has been previously considered. Therefore, in order to detect persistent changes, a DMSA scan should be performed more than 5 months after UTI.
Article
To reassess the impact of renal ultrasonography on the care of children with first febrile urinary tract infection (UTI) we conducted a computer search and review of medical records of (1) all children who were admitted to our hospital with first febrile urinary tract infection and underwent renal ultrasonography during a 25-month period beginning February 1, 1995, (2) all children diagnosed by ultrasound to have hydronephrosis during the same time period. Of a total of 124 patients with UTI, renal ultrasound appeared normal or showed evidence of acute pyelonephritis in 105 (84.7%), and in another nine (7.2%) it showed only minor findings. In 10 children (8.1%) ultrasound showed hydronephrosis and/or hydroureter. In eight of the latter 10, voiding cystourethrography showed vesicoureteral reflux; in one, posterior urethral valves; and in one, who had a unilateral nonobstructed dilatated system, cystography appeared normal. Except for the last patient, who was given prophylactic antibiotics and continued to have urinary tract infections, in no other case did ultrasound alone have any impact on the patient's management. Four children with both abnormal-appearing renal ultrasound and voiding cystourethrography required surgical intervention. One hundred of the 124 children had a voiding cystourethrogram. In 38 children it detected vesicoureteral reflux and, in another two, bladder abnormalities. Thirty-five of those with abnormal-appearing cystogram but without an indication for surgery were given prophylactic antibiotics. During the same 25-month period, 63 children without urinary tract infection were diagnosed by ultrasound with hydronephrosis. In 45 of them (71.4%) the urologic abnormality had already been detected by prenatal ultrasound. Fourteen of these 45 children (31.1%) required surgery, all for congenital anomalies related to obstructive uropathy. We conclude that routine renal ultrasonography in children with first urinary tract infection has negligible influence on their clinical management. This seems to be due to the recent widespread use, in industrialized countries, of maternal-fetal ultrasonography, which already detects a significant number of children with congenital obstructive uropathy prenatally. On the other hand imaging of the lower urinary tract is of high yield and contributes significantly to patient care. Therefore, whereas imaging of the lower urinary tract should continue to be done routinely in children with first urinary tract infection, renal ultrasound may be reserved for more select cases.
Article
The strategy for morphological investigations in children with acute pyelonephritis (APN) remains debatable. We studied 70 children (median age 2.0 years) admitted with a first episode of pyelonephritis using a high-resolution ultrasound technique (RUS) and compared the results with 99m technetium-dimercaptosuccinic acid (DMSA) renal scintigraphy. The DMSA scan was abnormal in 62 children (89%). However, using a high-frequency transducer we found abnormal sonogram changes in 61 children (87%), consisting of an increased kidney volume in 42, and/or a thickening of the wall of the renal pelvis in 42, and/or a focal hyper- or hypoechogenicity in 36, and/or a diffuse hyperechogenicity in 31 children. Micturating cystourethrography was performed in all children, revealing vesicoureteral reflux (VUR) in 22 (31%). Among those children with VUR, 4 had a normal DMSA scan, 2 an abnormal RUS, and 2 a normal DMSA scan and RUS. Our data suggest that B-mode RUS performed with a high-frequency transducer by a trained radiologist is nearly as sensitive as the DMSA scan in diagnosing renal involvement in children with unobstructed APN and in predicting VUR.
Article
To evaluate blood pressure in a population-based cohort with urographic renal scarring after childhood urinary tract infection. Follow-up investigation 16-26 years after the first recognized urinary tract infection. University out-patient clinic for children with urinary infections serving the local area. From the original cohort of 1221 consecutive children with first urinary tract infection diagnosed during 1970-1979, 57 of 68 with non-obstructive renal scarring participated as well as 51 matched subjects without scarring. 24 h ambulatory blood pressure. Acceptable blood pressure monitorings were obtained from 53 individuals with and 47 without scarring. There were no significant differences between the two groups even when only patients with the most extensive scarring (individual kidney clearance < 30 ml/min per 1.73 m2) or patients with bilateral scarring were compared with the non-scarring group. Mean systolic or diastolic blood pressure above +2 SD were found in 5/53 (9%) and 3/47 (6%) in the scarring and non-scarring group, respectively. Plasma renin activity, angiotensin II and aldosterone concentrations were not significantly different, but atrial natriuretic protein was significantly higher in the scarring group (P = 0.004). This study demonstrates a low risk of hypertension two decades after childhood urinary tract infection. It should be stressed that the patients with renal scarring were under close supervision throughout childhood. Those with scarring had higher concentrations of atrial natriuretic protein which might indicate a counter-regulation mechanism.
Article
The objective of this study was to evaluate the findings of 99mTc-DMSA renal scintigraphy in children with their first acute febrile urinary tract infection in relation with several clinical-biological parameters and other imaging studies and a long-