Severe Vesicoureteral Reflux Research Articles

Impact of antibiotic prophylaxis on urinary tract infection recurrence in children

Introduction: Given the potential consequences associated with urinary tract infections (UTI), it has become standard practice to use continuous antibiotic prophylaxis (CAP) in children, even if controversial. We reviewed the effectiveness of CAP on recurrent UTI in a pediatric population to determine if equipoise remains and allow for a placebo control group to study the effectiveness of the vaccine MV140. Method: We completed a rapid review. We searched Medline, Embase and the Cochrane Library and data extraction was completed by a single reviewer. Our search criteria were 2005–2022, English and French language, randomized controlled trials (RCTs) and systematic reviews only. The population was 19 years and younger, including: vesicoureteral reflux (VUR), congenital anomalies of the kidneys and urinary tracts (CAKUT), and bladder and bowel dysfunction (BBD). Results: Three RCTs and three systematic reviews found a benefit for CAP, mostly for a population with VUR, and those with severe VUR have more benefit. Most studies were not able to show a difference in the rate of UTIs or new renal scars (NRS). Three RCTs found a deleterious effect with CAP. Other studies were able to prove a benefit for patients with dilatation of the urinary tract without obstruction and high-grade VUR combined with BBD. The major adverse event found was antimicrobial resistance. Conclusions: High-risk patients benefit from CAP. The potential consequences of UTIs makes it unethical to use a placebo-only control group for them; however, CAP use seems difficult to justify in a low-risk population.

Urodynamic Abnormalities in Children with Primary Bilateral Vesicoureteral Reflux.

Bilateral vesicoureteral reflux (VUR) has been associated with poor long-term prognosis, and research focusing exclusively on its effect on urinary bladder function is lacking. This study aims to assess the urodynamic characteristics of children with bilateral VUR and identify factors influencing renal function. A retrospective analysis was performed on children diagnosed with bilateral VUR who underwent urodynamic examination in the outpatient department of our institution from January 2019 to January 2023. All patients underwent comprehensive assessments, including voiding cystourethrography, urinary system ultrasound and urodynamic examination, to analyse the urodynamic features associated with different clinical characteristics. The study included 148 children with bilateral VUR, amongst whom 92 (62.2%) exhibited urodynamic abnormalities, including idiopathic detrusor overactivity (DO) in 30 cases (20.3%) and dysfunctional voiding (DV) in 58 cases (39.2%). DV was prevalent in children under 5 years of age, whereas idiopathic DO was predominantly observed in children older than 2 years of age. Children older than 5 years of age exhibited a trend towards reduced bladder volume, whereas those younger than 2 years of age often had increased bladder volume and residual urine. Multivariate analysis identified bilateral severe VUR as an independent risk factor for abnormal estimated glomerular filtration rate. DV tends to be more common in younger children with larger bladder volumes and increased residual urine than in older children. By contrast, older children are more susceptible to idiopathic DO associated with smaller bladder volumes than younger children. Bilateral severe reflux increases the likelihood of renal functional abnormalities, which appear to be a consequence of congenital scarring rather than abnormalities in bladder function.

Neurogenic Bladder: A Rare Autonomic Sign in a Patient With Preserved Speech Variant (Zappella Variant) Rett Syndrome

Background: Rett syndrome is characterized by the loss of speech and purposeful hand movements, ambulation problems, and typical hand stereotypies. Preserved speech variant Rett syndrome (Zappella Variant) is a much less common form where speech is relatively preserved, from words to simple sentences. Lower urinary tract dysfunction and neurogenic bladder due to autonomic involvement have been only rarely reported in Rett syndrome. We aimed to emphasize neurogenic bladder due to autonomic dysfunction, which has very rarely been reported in the literature, in a patient with preserved speech variant Rett syndrome, a rare form of the Rett syndrome. Case presentation: A 7-year-old female patient who had been diagnosed with severe vesicoureteral reflux and neurogenic bladder when 11 months old due to the inability to urinate was suspected of suffering from Rett syndrome after intense eye contact and the stereotypic movement of hand wringing were observed. The patient could talk with phrases and walk and had purposeful hand movements. The presence of the c.961C>T (p.Arg321Trp) mutation in the C terminal region of the MECP2 gene was demonstrated with Sanger sequencing. The patient is currently 13 years old and is receiving special education and continues to be monitored for chronic renal disease at the pediatric nephrology department. Conclusion: The presence of hand stereotypies and intense eye pointing could indicate the Zappella variant Rett syndrome in a female patient who has developmental problems, can talk, has purposeful hand skills. Rett syndrome patients can also have lower urinary tract dysfunction although this is less common than cardiac, respiratory and gastrointestinal autonomic involvement. The development of intermittent urinary retention and vesicoureteral reflux may be associated with neurogenic bladder caused by autonomic involvement should be considered in these patients and one must be aware of the complications.

The Role of Varied Sonographic Criteria for Predicting Treatment and Prognosis of Antenatal Hydronephrosis: A Retrospective Cohort Study

Objective: This study aimed to compare the Society of Fetal Urology (SFU) guidelines, the anteroposterior pelvic diameter (APD), and the urinary tract dilation (UTD) classification criteria for predicting the prognosis of antenatal hydronephrosis (AH). Materials and Methods: This was a retrospective analysis of the relationship among the three classification criteria and their contribution to the diagnosis and prognosis of possible AH in a cohort of neonates. Results: This study was a retrospective review of 290 neonates. The mean age was 16.4 ± 9.0 days, and 33% of the study population comprised female babies. An image review demonstrated that 35% of the patients had severe vesicoureteral reflux (VUR), 22% exhibited severe obstruction, 40% had transient hydronephrosis, and 9% required surgery. The antenatal SFU grading criteria demonstrated a significant relationship with severe obstruction, and the postnatal SFU grading was related to the severity of VUR. The highest sensitivity for the presence of VUR for surgical intervention was obtained for prenatal SFU-1 (100%). The highest specificity was for prenatal SFU-4 (96%) for the presence of VUR, prenatal SFU-4 (99%), and postnatal SFU-4 (94%) for surgical intervention. Conclusion: No reliable sonographic findings were found to predict VUR or severe ureteropelvic junction obstruction. The SFU grading during the postnatal period may predict VUR with low sensitivity and specificity. However, all three classification criteria contributed to the evaluation of the need for treatment in this cohort.

Therapeutic Management of Children with Vesicoureteral Reflux.

Contrasting data refer to therapies for vesicoureteral reflux (VUR), such as surgical treatments and continuous antibiotic prophylaxis (CAP). This study evaluated the effectiveness of these approaches in children with VUR, analyzing the recurrence of febrile urinary tract infections (UTIs) and the resolution of VUR after the treatment. A total of 350 pediatric patients underwent contrast-enhanced voiding urosonography (ceVUS) to diagnose a VUR, whereas renal scintigraphy evaluated potential scars. After 12 months from the treatment, the VUR, the relapse of febrile UTIs, and reflux-related nephropathy were analyzed. Twenty-seven children had recurrent febrile UTIs after surgical therapy, with a greater rate of relapses observed in III and V VUR grades. Thirteen patients who underwent surgery had scars, independently of VUR grades and gender, with evidence of chronic renal failure at the end of the follow-up period. A total of 140 subjects were treated with CAP, and 30% of them continued to suffer from febrile UTIs. Ninety-five patients with VUR underwent ceVUS after 12 months, with persistent reflux in fifty-two patients. All of them had severe VUR, correlating with the age at diagnosis and gender. CAP therapy prevented scarring better than surgery, especially in children with III and V grades of VUR. A late onset of VUR or VUR involving neonatal patients is rarely a reversible process. This study identified predictors of success or failure of surgical or CAP therapies, evaluating the relapse of UTIs or persistent reflux after the treatment and giving prognostic information in children with VUR.

The Utility of Noninvasive Urinary Biomarkers for the Evaluation of Vesicoureteral Reflux in Children.

Vesicoureteral reflux (VUR) is one of the most important disorders encountered in pediatric nephrology due to its frequency and potential evolution to chronic kidney disease (CKD). The aim of our study was to identify noninvasive and easy-to-determine urinary markers to facilitate the diagnosis and staging of VUR. We performed a cross-section study including 39 patients with VUR followed over three years (August 2021-September 2023) and 39 children without urinary disorder (the control group). We measured the urinary concentration of interleukin-6 (IL-6), cathelicidin (LL-37), and neutrophil gelatinase-associated lipocalin (NGAL) in VUR and healthy controls. Moreover, we analyzed the correlation between these biomarkers and the presence of renal scars (RS), reflux nephropathy (RN), and CKD. The NGAL concentrations were significantly higher in patients with VUR than in the controls (p = 0.02). Regarding the severity of the reflux, NGAL/creatinine and LL-37/creatinine were positively correlated with severe reflux (p = 0.04, respectively, p = 0.02). In patients with VUR and RS, LL-37/creatinine was significantly lower (p = 0.01). LL-37/creatinine with an AUC of 0.71 and NGAL/creatinine with an AUC of 0.72 could be acceptable diagnostic tests for severe VUR. In conclusion, urinary IL-6, NGAL, and LL-37 could serve as valuable markers for diagnosing and predicting outcomes in patients with VUR and RN.

Diagnostic Values of Immature Granulocytes Detected by the Sysmex XN 9000 Hematology Analyzer in Children with Urinary Tract Infections.

Immature granulocytes (IGs) are used as markers of infection and systemic inflammation. We aimed to investigate the diagnostic value of IGs in children with urinary tract infections (UTIs). Children with their first UTIs were included in this observational study. Blood samples were obtained before antibiotic therapy. The blood analysis was repeated 2 weeks after the treatment ended. In total, 194 children (95 with febrile UTI, 58 with cystitis, and 41 controls) were included. The percentage of IGs (IG%) and IG count (IGC) measured at the time of admission were higher in the patients with febrile UTI than in the patients with cystitis and the controls (P = 0.000). The IGC and IG% after treatment were higher in patients with renal scarring than in those without scarring (P = 0.012 and P = 0.021, respectively). Cox's regression analysis showed the significant associations of renal scarring with both IGC and IG% (hazard ratio: 8.181, P = 0.002; hazard ratio: 5.106, P = 0.033, respectively). Both IGC and IG% were positively associated with severe vesicoureteral reflux (VUR) [odds ratio (OR): 22.235, P = 0.025; OR: 15.597, P = 0.038, respectively]. In conclusion, the IG% and IGC, which can be easily measured in a routine complete blood count without the need for additional effort, could be used as biomarkers for predicting febrile UTI, renal scarring, and severe VUR in children.

EVALUATION OF VESICOURETERAL REFLUX IN NEUROGENIC BLADDER DYSFUNCTION AND CHOICE OF TREATMENT STRATEGY

The aim of the research is to enhance the treatment outcomes of vesicoureteral reflux (VUR) that arises in the context of neurogenic bladder dysfunction (NBD) by developing a systematically justified approach for selecting treatment strategies for patients and improving existing treatment methods accordingly.
 Materials and Methods. A clinical examination was conducted on 279 patients with vesicoureteral reflux (VUR) that occurred in the context of neurogenic bladder dysfunction (NBD). Out of these, 87 patients received conservative treatment. The study design employed was a longitudinal (prospective) case-control study. Randomization was not used. Inclusion criteria required the presence of VUR in patients concurrently with NBD. Patients with Grade V VUR were excluded from the study. Clinical and laboratory manifestations of VUR and its complications were studied and assessed. A comprehensive evaluation of the severity of VUR and treatment effectiveness was performed. Patients were divided into three groups based on the proposed system "Method for a Comprehensive Assessment of the Severity of Vesicoureteral Reflux Disease and Treatment Effectiveness."
 Results. Vesicoureteral reflux (VUR) was most frequently observed in patients between the ages of 6 and 10, constituting 44.4% of the cases. VUR of Grade III-IV was more commonly diagnosed in patients under 5 years of age. Complaints related to urinary disorders tended to decrease or disappear with age (t= -0.1533; p=0.010). As patients grew older (after 7-8 years), the frequency of pyelonephritis exacerbations decreased (t= -0.1344; p=0.025). However, dilatation of the upper urinary tract (t=0.2157; p=0.001) and deterioration of kidney function (t=0.2354; p=0.001) were observed more frequently. Inflammation of the urinary tract occurred more frequently in women (t=0.1419; p=0.018), while renal function impairment due to VUR was more common in men (t= -0.1733; p=0.004).
 Conclusions. Most clinical and laboratory manifestations of vesicoureteral reflux (VUR) do not correlate with its grade. A reverse correlation was found between the grade of VUR and age, and a direct correlation with leukocyturia. Urinary disorders, leukocyturia, and the frequency of pyelonephritis exacerbations are components of VUR's clinical presentation that affect the quality of life and are among the first to change due to treatment, primarily through the normalization of bladder function. Clinical manifestations and complications of VUR negatively impact the quality of life in 66.2% of patients. The assessment of treatment effectiveness takes into account the grade of VUR and the complex of main clinical manifestations and complications, which can be considered using the proposed system "Method for a Comprehensive Assessment of the Severity of Vesicoureteral Reflux Disease and Treatment Effectiveness."

Quantification of vesicoureteral reflux using machine learning

The radiographic grading of voiding cystourethrogram (VCUG) images is often used to determine the clinical course and appropriate treatment in patients with vesicoureteral reflux (VUR). However, image-based evaluation of VUR remains highly subjective, so we developed a supervised machine learning model to automatically and objectively grade VCUG data. A total of 113 VCUG images were gathered from public sources to compile the dataset for this study. For each image, VUR severity was graded by four pediatric radiologists and three pediatric urologists (low severity scored 1-3; high severity 4-5). Ground truth for each image was assigned based on the grade diagnosed by a majority of the expert assessors. Nine features were extracted from each VCUG image, then six machine learning models were trained, validated, and tested using 'leave-one-out' cross-validation. All features were compared and contrasted, with the highest-ranked then being used to train the final models. F1-score is a metric that is often used to indicate performance accuracy of machine learning models. When using the highest-ranked VCUG image features, F1-scores for the support vector machine (SVM) and multi-layer perceptron (MLP) classifiers were 90.27% and 91.14%, respectively, indicating a high level of accuracy. When using all features combined, F1 scores were 89.37% for SVM and 90.27% for MLP. These findings indicate that a distorted pattern of renal calyces is an accurate predictor of high-grade VUR. Machine learning protocols can be enhanced in future to improve objective grading of VUR.

The correlation between ureteric orifice morphology and primary vesicoureteral reflux grade and the impact on the effectiveness of endoscopic reflux correction

Early diagnosis and treatment of primary vesicoureteral reflux (VUR) are essential for preserving renal function. The study explored whether preoperative cystoscopic grading of refluxing ureteric orifices (UO) correlated with their shape in an institution with non-performance of hydrodistention of the UO in the diagnosis and grading of VUR. We also assessed the relationship between the UO shape and VUR grade with the effectiveness of endoscopic correction of primary VUR in children. This retrospective study included consecutive patients ≤15 years treated for primary VUR. The reflux grade was based on the results of preoperative voiding cystourethrography as mild, moderate, or severe. Fifty-one patients with 77 renal refluxing units (RRU) underwent endoscopic treatment with Deflux®. VUR was bilateral in 51% of patients. VUR was mild in 13%, moderate in 53%, and severe in 34% of cases. The patients with mild and moderate VUR had stadium-shaped UOs in 60% and 54% RRUs, respectively. Horseshoe-shaped UOs constituted 42% of UOs in patients with severe VUR, followed by 31% of golf-hole UOs. The reflux resolution rate after the first endoscopic injection was 84%. The preoperative VUR grade correlated with UOs shape (p<0.001). No significant correlation between UOs configuration and the outcome of endoscopic treatment was seen (p=0.452). The preoperative VUR grade negatively correlated with a favorable endoscopic treatment (p=0.043). Our data indicate ureteral orifice shapes are closely related to preoperative VUR grade. There was no correlation between the UO configuration and the success rate of endoscopic treatment of VUR, in contrast to the significant negative correlation between the VUR grade and the success rate of endoscopic treatment.

Vesicoureteral reflux severity is not associated with unplanned urinary catheterization or length of hospital stay after ureteroneocystostomy

Vesicoureteral reflux (VUR) is a common urologic condition affecting approximately 1% of all children. Surgical success often depends on the grade of VUR, as patients with grades 4 or 5 have been have a greater risk for postoperative complications. Unplanned urinary catheter placement (UCP) postoperatively and prolonged length of hospital stay (LOS) are indicative of unexpected complications. The association between VUR severity and such metrics remain unclear. The study's objective is to determine if the severity of VUR is associated with higher rates of UCP or prolonged LOS after ureteroneocystostomy (UNC). The 2020 National Surgical Quality Improvement Program Pediatric database was analyzed for patients with VUR. A total of 1742 patients were initially evaluated with 1373 meeting exclusion criteria. The patients were divided into 3 groups of varying voiding cystourethrogram (VCUG) or radionuclide cystogram (RNC) severity: VCUG Grade 1 or RNC Grade 1 (Group A), VCUG Grade 2 or 3 or RNC Grade 2 (Group B), and VCUG Grade 4 or 5 or RNC Grade 3 (Group C). Basic statistical analysis was performed, and logistic regression was performed with both UCP and LOS as dependent variables. Among the 1373 patients, 2.9% were included in Group A, 32.5% were in Group B, and 64.6% were in Group C. Significant differences were found among the groups for mean age, gender, inpatient status, rate of congenital malformation, ureteral stents, and ASA classification. Regarding surgical treatment, differences were also found comparing mean operative time, LOS, laterality and type of procedure, urine culture results, rates of UTI, surgical site infections, postoperative returns to the emergency department, and unplanned procedures and catheterization. Multivariate analysis demonstrated no significant association between the rate of UCP and VUR severity, while postoperative UTI and unplanned procedure were both independent factors associated with UCP postoperatively. Additionally, postoperative UTI, ASA classification, mean operation time, ureteral stent placement, unplanned procedure, and UCP were independent factors found to contribute to LOS. Greater VUR severity does not appear to increase the need for catheterization or prolong hospital stay, while the development of a UTI postoperatively or having an additional unplanned procedure are associated with an increased likelihood of both. The postoperative course after UNC also appears to be influenced more so by other factors such as the operative approach and whether complications arise.

A quantitative analysis of voiding cystourethrogram features confirms the association between high-grade vesicoureteral reflux with male sex, younger age, and hydronephrosis.

Vesicoureteral reflux (VUR) is commonly diagnosed in the workup of urinary tract infections or hydronephrosis in children. Traditionally, VUR severity is graded subjectively based on voiding cystourethrogram (VCUG) imaging. Herein, we characterized the association between age, sex, and indication for VCUG, by employing standardized quantitative features. We included renal units with a high certainty in VUR grade (>80% consensus) from the qVUR model validation study at our institution between 2013 and 2019. We abstracted the following variables: age, sex, laterality, indication for VCUG, and qVUR parameters (tortuosity, ureter widths on VCUG). High-grade VUR was defined as grade 4 or 5 The association between each variable and VUR grade was assessed. A total of 443 patients (523 renal units) were included, consisting of a 48:52 male/female ratio. The median age at VCUG was 13 months. Younger age at VCUG (<6 months) was associated with greater odds of severe VUR (odds ratio [OR] 2.0), and there was a weak correlation between age and VUR grade (ρ=-0.17). Male sex was associated with increased odds of high-grade VUR (OR 2.7). VCUGs indicated for hydronephrosis were associated with high-grade VUR (OR 4.1) compared to those indicated for UTI only. Ureter tortuosity and width were significantly associated with each clinical variable and VUR severity. Male sex, younger age (<6 months), and history of hydronephrosis are associated with both high-grade VUR and standardized quantitative measures, including greater ureter tortuosity and increased ureteral width. This lends support to quantitative assessment to improve reliability in VUR grading.

Assessing the Utility of Tamsulosin in Delaying Progression to Clean Intermittent Catheterization and End-stage Renal Disease in Patients With Posterior Urethral Valves: Are We Postponing the Inevitable?

To assess whether tamsulosin may aid emptying of the lower urinary tract in posterior urethral valves patients, mitigating the likelihood of progressing to clean intermittent catheterization (CIC) or need for renal replacement therapy. We reviewed a prospective institutional database containing posterior urethral valves patients treated between January 2000 and January 2022. After assessing baseline characteristics, Kaplan-Meier survival curves and log-rank tests were generated to assess differences in clinically significant outcomes (progression to CIC, dialysis, or kidney transplantation) between those prescribed tamsulosin and those who were not. A total of 179 patients were included. Fifty-nine patients received tamsulosin prior to initiation of CIC (group 1), and 120 did not (group 2). The baseline characteristics were similar between the two groups, except for anticholinergic use (tamsulosin group - 35/59 vs no tamsulosin - 32/120, P<.001). The median age at tamsulosin initiation was 26.0 months (IQR 15.5-48.6) and the median time from initiation of tamsulosin to progression to CIC was 52.6 months (IQR 10.1-69.3). Kaplan-Meier survival curves showed that patients on tamsulosin were less likely to progress to CIC (P=.021), however, there was no difference in progression to dialysis or kidney transplantation. A Cox-regression analysis controlling for baseline characteristics, including age, anticholinergic use, vesicoureteral reflux severity, and CKD stage at 1-year of life, showed a consistent effect of tamsulosin in delaying progression to CIC (HR 0.444 95%CI 0.218-0.902, P=.025). While tamsulosin may delay CIC, it does not appear to delay progression to end-stage renal disease. Additional studies exploring specific patient factors are required to determine the timing and subset who may benefit the most from tamsulosin.

The Role of Urinary NGAL in the Management of Primary Vesicoureteral Reflux in Children.

Vesicoureteral reflux (VUR) is the most frequent congenital urinary tract malformation and an important risk factor for urinary tract infections (UTIs). Up to 50% of children with VUR may develop reflux nephropathy (RN), and the diagnosis and monitoring of renal scars are invasive and costly procedures, so it is paramount to find a non-invasive and accurate method to predict the risk of renal damage. Neutrophil gelatinase-associated lipocalin (NGAL) has already proven to be a good predictive biomarker in acute kidney injuries, but there are few studies that have investigated the role of NGAL in primary VUR in children. Our aim is to review the predictive value of urine NGAL (uNGAL) as a non-invasive biomarker of RN in children with primary VUR, as well as its ability to predict the evolution of chronic kidney disease (CKD). Based on our analysis of the available original studies, uNGAL can be an accurate and reliable biomarker of RN and its progression to CKD. Some studies suggested a good correlation between VUR severity and uNGAL levels, but other studies found no significant correlation. The relationship between VUR severity and uNGAL levels is likely complex and influenced by factors such as UTIs, the timing of the urine sample collection, and the age and overall health of the patient.

An infant girl with bilateral multicystic dysplastic kidney: a case report

Multicystic dysplastic kidney (MCDK) is a congenital kidney abnormality with an overall incidence rate of 1/4300 live births that is more prevalent in males than females. Here, we describe a rare case of bilateral MCDK complicated by hypertension, severe vesicoureteral reflux (VUR), and urinary tract infection (UTI), who stabilized during hospitalization with prospective kidney transplantation due to poor prognosis. Since bilateral MCDK is a rare disease with numerous complications and a poor prognosis, patient symptom management and treatment may be more challenging.

Urine Neutrophil Gelatinase Associated Lipocalin as a Predictor of Vesicoureteral Reflux and Renal Parenchymal Damage: A Systematic Review

Background: Vesicoureteral reflux (VUR) is the most common congenital urinary tract abnormality in children. Renal parenchymal damage is the most devastating complication of severe undiagnosed VUR. Different diagnostic biomarkers have been introduced as alternatives for radiologic evaluation in these patients. This review article aimed to increase the knowledge about the role of urine neutrophil gelatinase-associated lipocalin (uNGAL) in children affected by primary VUR and renal parenchymal damage. Methods: A systematic review of PubMed, Scopus, Web of Science, ProQuest, and Ovid was conducted in September 2022 to retrieve studies that investigated the correlation between uNGAL or uNGAL/Cr excretion and primary VUR in male/female patients younger than 18 years of age. Patients with secondary VUR, age older than 18 years, infectious or inflammatory disorders, obstructive uropathies, and acute or chronic kidney diseases were excluded. Two reviewers independently screened the titles and abstracts of the search results and then assessed the full texts selected from the pertinent studies. Results: Eighteen research articles with a total sample of 699 patients were found to measure uNGAL in VUR or renal scarring. UNGAL or uNGAL/Cr had increased excretion in the majority of children with primary VUR or RPD, with a positive or no correlation to the severity of VUR. Conclusions: Several studies addressed uNGAL and uNGAL/Cr as putative biomarkers for the prediction of VUR or reflux-associated RPD.

La profilassi antibiotica nei lattanti con reflusso vescicoureterale di grado elevato: più svantaggi che vantaggi

Antibiotic prophylaxis in infants with high-grade vesicoureteral reflux: more disadvantages than advantages The effectiveness of continuous antibiotic prophylaxis in high-grade reflux (III-V) is controversial. This prospective multicenter randomized open-label phase 3 study highlights how in infants with high-grade reflux without previous UTI, continuous antibiotic prophylaxis guarantees a small but significant benefit in terms of prevention of a first UTI compared to placebo (21.2% vs 35.6%, 95% CI 0.35-0.86, p= 0.008), despite an increased incidence of infections from non-coli germs and increased antibiotic resistance. Furthermore, no difference was highlighted between the two groups in terms of long-term renal scarring and renal function two years after enrollment. The use of continuous antibiotic prophylaxis, in patients without previous history of urinary tract infection must therefore be evaluated judiciously depending on the patient's sex, the severity of vesicoureteral reflux, the presence of bladder dysfunction.

Cases of Pediatric Pyelonephritis: A Single-Center Retrospective Study from an Extended-Spectrum β-Lactamase-Producing Escherichia coli Endemic Area in Japan.

Extended-spectrum β-lactamase (ESBL)-producing Escherichia coli has been increasingly recognized as the cause of upper urinary tract infection (UTI) in children. We have been using flomoxef at our department since 2017 as the first-line empiric therapy for children diagnosed with UTIs, and we avoid using carbapenems, which are considered the first-line treatment for ESBL-producing E. coli. However, reports on the use of flomoxef for UTIs are limited, especially for pediatric patients. The presence of vesicoureteral reflux at the onset of pyelonephritis is a concern. Severe vesicoureteral reflux can lead to repeated UTI and future deterioration of renal function, but the indication for voiding urethrography, which closely examines the presence of vesicoureteral reflux complications, is controversial. We retrospectively reviewed the laboratory findings, treatment, and clinical course of 96 pyelonephritis cases experienced at our department over a 7-year period from April 2014 to March 2021. ESBL-producing E. coli were identified as the cause of pyelonephritis in 51% of cases, and this value was significantly higher (88%) in 2017. No significant differences were found in the febrile period or recurrence rate between the flomoxef-initiated group and other antibiotics groups. We also examined clinical indicators to predict vesicoureteral reflux and found no significant differences in ultrasonographic findings of hydronephrosis. In the present series, 51% of all pyelonephritis cases were found to be caused by ESBL-producing E. coli, with a significant increase in recent years. Flomoxef may be a useful alternative to carbapenem for ESBL-producing E. coli and the initial antibiotic of choice for upper UTIs in children. The indication for voiding cystourethrography should be carefully determined.

Cutoff Value of Ureteral Diameter Ratio for Predicting Spontaneous Resolution of Vesicoureteral Reflux

Purpose: The five-grade international scale for vesicoureteral reflux (VUR) has been the mainstay for describing VUR severity. The concept of the distal ureteral diameter to the L1–L3 vertebral body distance ratio has been validated. We validated the ureteral diameter ratio (UDR) for predicting VUR outcomes and determined the cutoff value for spontaneous resolution. Materials and Methods: This retrospective review included children with primary VUR and detailed serial voiding cystourethrograms (VCUGs) between March 2005 and December 2016. Patient characteristics, VUR grade, laterality, UDR, laboratory data, and follow-up results were collected. UDR was estimated as the largest distal ureteral diameter within the pelvis divided by the distance of the L1–L3 vertebral bodies. The primary outcome was the prediction of spontaneous VUR resolution. The secondary outcome was the determination of the cutoff value of UDR in the present cohort. Results: We recruited 101 children (59 boys and 42 girls) diagnosed as having primary VUR based on VCUGs at a mean age of 23.48 months. VUR resolved spontaneously in 31 (30.7%) children, 40 (39.6%) children had persistent disease, and 30 (29.7%) received surgical correction. In univariate analysis, laterality, VUR grade, and UDR were significantly associated with spontaneous resolution (P = 0.017, P = 0.026, and P = 0.001, respectively). Multivariate analysis revealed UDR as the prognostic factor for spontaneous VUR resolution (odds ratio, 4.167; P = 0.023). The area under the curve of UDR indicates that the prediction accuracy was 0.74. The optimal cutoff value for UDR in this study was 0.264 (sensitivity, 0.81 and specificity, 0.63). Conclusion: UDR is superior to the VUR grade for predicting spontaneous VUR resolution. Our findings add significant prognostic value for children with primary VUR. A cutoff value of 0.264 may assist with clinical assessment and future management.

Evaluation of Pediatric Patients with a Diagnosis of Ureterocele.

The presence and clinical importance of vesicoureteric reflux in patients with a double collecting system are being questioned. Therefore, the role of voiding cystourethrography in the management of patients with ureterocele is unclear. This study aimed to evaluate patients with a ureterocele in terms of urinary tract infection (UTI) and vesicoureteral reflux (VUR). The cases who were admitted to the Pediatric Nephrology Clinic of Health Sciences University Tepecik Training and Research Hospital between 2012 and 2022 and were diagnosed with ureterocele were evaluated retrospectively. Demographic, clinical, and laboratory data were obtained from file records. All patients diagnosed with ureterocele and voiding cystourethrography (VCUG) were evaluated. A total of 24 (female 13 (54.2%)) children were included. The reasons for admission were antenatal hydronephrosis in 13 (54.2%) patients, UTI in 9 (37.5%) patients, and incidentally diagnosed ureterocele in 2 (8.3%) patients. Urinary tract infection was observed in 20 patients at admission, recurrent UTI in 21 patients at follow-up, preoperative pyelonephritis in 12 patients. VUR was found in 11 patients, and severe VUR (≥stage 3) was found in 9 patients. Ten patients had ipsilateral hydronephrosis, and 14 patients had a double collecting system. The presence of VUR was found to be associated with female gender, UTI at admission, and recurrent UTI at follow-up (p &lt; 0.05). However, there was no difference between groups with or without VUR in terms of ipsilateral hydronephrosis, scar formation, and the need for surgery (p &gt; 0.05). We could not demonstrate any criteria to select patients to receive VCUG; on the other hand, VUR did not cause more kidney damage. Our study supports the need for more scientific data to determine management in patients with ureterocele.