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Primary vesicoureteral reflux (VUR) is one of the most common urological abnormalities in infants and children. The association of VUR, urinary tract infection (UTI) and renal parenchymal damage is well established. The most serious complications of VUR-associated reflux nephropathy are hypertension and proteinuria with chronic kidney disease. Over the past two decades, our understanding of the natural history of VUR has improved, which has helped to identify patients at increased risk of both VUR and VUR-associated renal injury. The main goals in the treatment of paediatric patients with VUR are the prevention of recurrent UTIs and minimizing the risk of renal scarring and long-term renal impairment. Currently, there are four options for managing primary VUR in infants and children: surveillance or intermittent treatment of UTIs with management of bladder and bowel dysfunction; continuous antibiotic prophylaxis; endoscopic subureteral injection of tissue-augmenting substances; and ureteral reimplantation via open, laparoscopic or robotic-assisted surgery. Current debates regarding key aspects of management include when to perform diagnostic imaging and how to best identify the paediatric patients that will benefit from continuous antibiotic prophylaxis or surgical intervention, including endoscopic injection therapy and minimally invasive ureteral reimplantation. Evolving technologies, such as artificial intelligence, have the potential to assist clinicians in the decision-making process and in the individualization of diagnostic imaging and treatment of infants and children with VUR in the future., (© 2024. Springer Nature Limited.)

Background: 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., Methods: 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., Results: 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., Conclusions: 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., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s).)

Vesicoureteral reflux (VUR) is a pathological condition contradistinguished by monolateral or bilateral retrograde flow of urine from the bladder to the ureter and to the kidney. If not properly recognized and treated, VUR can potentially be associated to several complications such as recurrent infections and possible secondary scars with Chronic Kidney Disease (CKD). Furthermore, it represents an important risk factor for nephrovascular hypertension. During the last 20 years, the diagnostic approach to this entity has passed through several, drastic changes: indeed, since its introduction in 1994 contrast-enhanced voiding urosonography (ceVUS) has gradually accompanied the voiding cystourethrography (VCUG) as alternative imaging technique for the diagnosis and staging of VUR. Despite a large number of papers has strongly encouraged its use in clinical practice, due to the lack of ionizing radiations and its high sensitivity rate, to date almost all the guidelines only include the VCUG for VUR diagnosis. The introduction of technologically advanced US software and the approval of the intravesical administration of ultrasound contrast agents by the Food and Drug Administration (FDA) and by the European Medicine Agency (EMA) have to induce the Scientific Community to a deep revaluation of the role of ceVUS in the diagnosis and follow-up of VUR: urosonography might extensively replace VCUG as the reference method, reserving to cystourethrography a role in the most complex anatomic settings for pre-surgical evaluation.

Background: Turner syndrome (TS) is a chromosomal disorder with various complications, including congenital anomaly of the kidney and urinary tract (CAKUT). However, its renal function remains poorly known. Therefore, this study aimed to evaluate renal function in TS of various ages from childhood to adulthood., Methods: We retrospectively analyzed 63 patients with TS who visited our hospital between 1989 and 2020, examined their renal morphology, and analyzed renal function by calculating the estimated glomerular filtration rate (eGFR) using formulas applicable for Japanese populations., Results: Renal morphological abnormality was observed in 22 cases (35.0%) (horseshoe kidney, 7 [11.1%]; hydronephrosis, 11 [17.5%]; duplex collecting system, 3 [4.8%]; and single unilateral kidney, 1 [1.6%]). We evaluated the eGFR of 47 subjects aged 2.8-39.3 years and classified them into Group 1 (with CAKUT, n = 15) and Group 2 (without CAKUT, n = 32). The eGFR at the first visit and the final follow-up was not statistically different between these groups. In Group 1 with CAKUT, the eGFR was not significantly different between that at the first visit and that at the final follow-up (p = 0.21). During the observation period (median, 7.9 years), the eGFR of all individuals in both groups gradually decreased with age, but did not fall < 60 mL/min/1.73 m 2 , which defines chronic kidney disease (CKD)., Conclusions: The renal function of TS remained normal in all cases during our investigation period, and no one developed CKD by the age of 40 years.

Background: Anti-glomerular basement membrane disease (GBM) disease is a rare autoimmune disease causing rapidly progressive glomerulonephritis and pulmonary haemorrhage. Recently, an association between COVID-19 and anti-glomerular basement membrane (anti-GBM) disease has been proposed. We report on a patient with recurrence of anti-GBM disease after SARS-CoV-2 infection., Case Presentation: The 31-year-old woman had a past medical history of anti-GBM disease, first diagnosed 11 years ago, and a first relapse 5 years ago. She was admitted with severe dyspnoea, haemoptysis, pulmonary infiltrates and acute on chronic kidney injury. A SARS-CoV-2 PCR was positive with a high cycle threshold. Anti-GBM autoantibodies were undetectable. A kidney biopsy revealed necrotising crescentic glomerulonephritis with linear deposits of IgG, IgM and C3 along the glomerular basement membrane, confirming a recurrence of anti-GBM disease. She was treated with steroids, plasma exchange and two doses of rituximab. Pulmonary disease resolved, but the patient remained dialysis-dependent. We propose that pulmonary involvement of COVID-19 caused exposure of alveolar basement membranes leading to the production of high avidity autoantibodies by long-lived plasma cells, resulting in severe pulmonary renal syndrome., Conclusion: Our case supports the assumption of a possible association between COVID-19 and anti-GBM disease.

&lt;b&gt;Background and Objective:&lt;/b&gt; Primary Nonsyndromic Vesicoureteral Reflux (PVUR) is a widespread genetic malformation and considered a prevalent Congenital Abnormality of the Kidney and Urinary Tract (CAKUT). Mutations in the &lt;i&gt;PAX2 &lt;/i&gt;gene have been associated with abnormalities in the kidney extending from CAKUT to oncogenic processes. The present study analyzes the &lt;i&gt;PAX2&lt;/i&gt; polymorphisms and their association with primary VUR in Saudi children patients from the Taif governorate. &lt;b&gt;Materials and Methods:&lt;/b&gt; Fifteen children with primary VUR were identified and screened for gene mutations in the &lt;i&gt;PAX2&lt;/i&gt; gene by direct sequencing method of purified Polymerase Chain Reaction (PCR) products of all exons to elucidate the correlation between &lt;i&gt;PAX2&lt;/i&gt; gene and VUR. &lt;b&gt;Results:&lt;/b&gt; Seven new variants have been defined. Three polymorphic missense variants in homozygous genotype form were found in intron 8 and detected in eight patients, One missense mutation was found in exon 10 in the site of transactivation domain and detected in ten patients and &lt;i&gt;in-silico&lt;/i&gt; analysis predicted it as a pathogenic one, Three mutations were found in exon 11 and detected in all patients as a compound homozygous. &lt;b&gt;Conclusion:&lt;/b&gt; &lt;i&gt;PAX2&lt;/i&gt;is important for normal kidney development and mutations in the gene possibly lead to disturbance in the protein structure and could be non-functional thus mutations in &lt;i&gt;PAX2&lt;/i&gt; may be one of the causes of PVUR in Saudi Arabia. Further investigation is necessary to understand the aetiology of disease and maybe other genes implicated in VUR.

In this study, our aim was to evaluate the significance of the change in renal pelvis anterior-posterior diameter (RPAPD) before and after micturition between vesicoureteral reflux (VUR)-positive and -negative patients to whom had voiding cystourethrography (VCUG) was performed.In this study, 69 children, age ranging from 0 to 12 years, were included. Before the VCUG imaging, the RPAPD was measured first with a full bladder and then after urination via ultrasound (US). The differences between in RPAPD measurements were noted and values compared made among VUR-positive and -negative children. Data distribution was inhomogeneous, and the Wilcoxon Sign Rank test was utilized instead of Student t test. There was no statistically significant difference in prevoiding and postvoiding RPAPD in VUR (+) and VUR (-) patients (P = 0.672). There was no statistically significant relation between VUR and the presence of hydronephrosis (P = 0.126). Vesicoureteral reflux is more common in patients with urinary tract infections (UTI) (P = 0.001). There was no statistically significant relationship between prevoiding and postvoiding RPAPD change and VUR diagnosis (P = 0,164).Ultrasound is the modality of choice for urinary system evaluation. Diagnosis of hydronephrosis via US is not sufficient in predicting VUR; however, indirect findings may reveal the diagnosis. A decrease in RPAPD in postvoiding US evaluation may not rule out the VUR diagnosis for this reason further imaging modalities, such as VCUG, should be taken into consideration for the patients with clinical suspicion.

Introduction: Since 2011 we have been following prospectively myelomeningocele patients treated in utero with particular interest to patients with sphincter weakness/deficiency. We investigated the changes of bladder pattern and upper urinary tract with time in children who underwent in utero repair and had low-pressure incontinence based on urodynamic evaluation (UE)., Materials and Methods: From the 120 patients in our database, 117 had at least one UE. Of these, 30 were classified as incontinent when leaking at low pressure (<40 cmH20). We reviewed clinical evaluation, urinary tract ultrasound, voiding cystourethrography (VCUG), and other UE parameters at first and last evaluation., Results: We found 30 cases (25.64%). Mean age at initial evaluation was 4.97 months followed by UE done initially at mean age of 5.73 months. Follow-up was 28.4 months. Febrile urinary tract infection has been found in four patients (13.3%), hydronephrosis in four patients, and bladder neck thickening in three (10%). The VCUG showed vesicoureteral reflux in three cases (3/27, 11.1%). A total of 90% of patients had detrusor overactivity with mean maximum detrusor pressure (33.37 cmH20). Only 16.67% of patients showed normal bladder capacity. From the 30 patients, 23 had at least two UE. We noticed a change of bladder pattern as follows: six patients became of high-risk pattern, five normal, and two with underactive bladder pattern. The average interval between the first and last UE was 25.5 months (median: 15 months)., Conclusion: We concluded that 43.47% of patients with low DLPP have kept the incontinent pattern. If the initial LPP was below 30 cmH20, 70% remained with the incontinet pattern., (© 2020 Wiley Periodicals LLC.)

Background: Bladder volume at the onset of vesicoureteral reflux (VUR) is an important prognostic indicator of spontaneous resolution and the risk of pyelonephritis., Objective: We aim to determine whether pediatric urologists and pediatric radiologists can accurately estimate the timing of reflux by examining voiding cystourethrogram (VCUG) images without prior knowledge of the instilled contrast volume., Materials and Methods: Total bladder volume and the volume at the time of reflux were collected from VCUG reports to determine the volume at the onset of VUR. Thirty-nine patients were sorted into three groups: early-/mid-filling reflux, late-filling and voiding only. Thirty-nine images were shown to three pediatric urologists and two pediatric radiologists in a blinded fashion and they were then asked to estimate VUR timing based on the above categories. A weighted kappa statistic was calculated to assess rater agreement with the gold standard volume-based report of VUR timing., Results: The mean patient age at VCUG was 3.1±2.9 months, the median VUR was grade 3, and 20 patients were female. Overall agreement among all five raters was moderate (k=0.43, 95% confidence interval [CI] 0.36-0.50). Individual agreement between rater and gold standard was slight to moderate with kappa values ranging from 0.13 to 0.43., Conclusion: Pediatric radiologists and urologists are unable to accurately and reliably characterize VUR timing on fluoroscopic VCUG. These findings support the recently published American Academy of Pediatrics protocol recommending the routine recording of bladder volume at the onset of VUR as a standard component of all VCUGs to assist in a more accurate assessment of the likelihood of resolution and risk of recurrent urinary tract infections.

Aims: To assess the urodynamic findings during the filling phase in neurogenic bladder patients with or without vesicoureteral reflux (VUR) who underwent sacral neuromodulation (SNM)., Methods: We retrospectively reviewed the records of 19 patients with neurogenic lower urinary tract dysfunction (NLUTD) who underwent SNM at our center from July 2018 to July 2019. Clinical data and video-urodynamic parameters were collected. VUR grading systems were used to evaluate upper urinary tract function., Results: The mean test duration was 24 ± 8.2 days. The urodynamic evaluation showed a significant increase in the mean maximum cystometric capacity (136.3 ± 118.2 vs 216.5 ± 137.8 mL; P = .0071) and compliance (8.7 ± 8.52 vs18.3 + 16.47 mL/H 2 O; P = .016), as well as a decrease in maximum intravesical pressure (57 ± 39.23 vs 36.58 ± 31.16 H 2 O; P = .0064). In the voiding phase, none of the patients had automatic urination at the baseline and testing phases. In 8 of 19 patients who had detrusor overactivity (DO), the DO disappeared (four patients) or was delayed (four patients). The VUR in 3 of 12 ureter units disappeared. The grade of VUR or the volume before VUR improved in 8 ureter units, and the remaining 1 did not change significantly. An implant was performed in 16 cases. After permanent implantation, all patients needed intermittent catheterization to empty the bladder., Conclusions: This retrospective study indicates that SNM can improve the urinary storage function of the bladder in appropriate patients with NLUTD. For patients with VUR, SNM can cure or reduce VUR by improving DO and bladder compliance., (© 2020 Wiley Periodicals, Inc.)

Congenital anomalies of the kidneys and urinary tracts (CAKUT) are disorders caused by defects in the development of the kidneys and their outflow tracts. The formation of the kidneys begins at week 3 and nephrogenesis continues until week 36, therefore, the kidneys and outflow tracts are susceptible to environmental risk factors that perturb development throughout gestation. Many genes have been implicated in kidney and outflow tract development, and mutations have been identified in patients with CAKUT. In severe cases of CAKUT, when the kidneys do not form, the fetus will not survive. However, in less severe cases, the baby can survive with combined kidney and outflow tract defects or they may only be identified in adulthood. In this review, we will cover the clinical presentation of CAKUT, its epidemiology, and its long-term outcomes. We will then discuss risk factors for CAKUT, including genetic and environmental contributions. Although severe CAKUT is rare, low nephron number is a much more common disorder with its effect on kidney function increasingly apparent as a person ages. Low nephron number appears to arise by the same mechanisms as CAKUT, but it differs in terms of the magnitude of the insult and the timing of when it occurs during gestation. By understanding the causes of CAKUT and low nephron number, we can begin to identify preventive treatments and establish clinical guidelines for how these patients should be followed., (Copyright © 2020 by the American Society of Nephrology.)

Radiological voiding cystourethrography has long been considered the gold standard for reflux testing in paediatric urology. Additional contrast-based procedures such as voiding urosonography or radionuclide cystography have been established in recent decades. Their main indication is reflux diagnosis after pyelonephritis in early infancy and childhood. The selection of the appropriate method is based on factors such as clinical question, availability, economic aspects, expenditure of human resources and time, and the goal of finding of method that provides as much information as possible while keeping radiation exposure to a minimum. Modern strategies aim for a risk-oriented, individual indication independent of the method of reflux testing., Competing Interests: Der Autor gibt an, dass kein Interessenkonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)

Purpose: We studied the effect of oxybutynin on bladder and upper urinary tract outcomes in infants following posterior urethral valve ablation., Materials and Methods: Patients younger than 12 months old who had undergone primary endoscopic valve ablation for posterior urethral valves were screened for eligibility. Patients who had undergone urinary diversion or had other conditions that could affect lower urinary tract function were excluded. Study patients were randomized to either oxybutynin (0.2 mg/kg 3 times daily) until toilet training or active observation. The study end points were serum creatinine, estimated glomerular filtration rate, hydronephrosis improvement, vesicoureteral reflux resolution, febrile urinary tract infection and toilet training., Results: A total of 49 infants (24 receiving oxybutynin and 25 undergoing observation) were enrolled between December 2013 and September 2015 and completed at least 1 year of followup. Oxybutynin was discontinued before toilet training in 5 patients due to facial flushing in 2, bladder and upper tract dilatation in 2, and cognitive changes in 1. After a median followup of 44.2 months (range 12 to 57.6) median serum creatinine and estimated glomerular filtration rate were not significantly different between the groups (p=0.823 and p=0.722, respectively). Renal units in the oxybutynin group had a greater likelihood of hydronephrosis improvement (61.9% vs 34.8%, p=0.011) and resolution of vesicoureteral reflux (62.5% vs 25%, p=0.023). Febrile urinary tract infection (29.2% vs 40%, p=0.404), completion of toilet training (70.8% vs 76%, p=0.748) and age at toilet training (p=0.247) did not differ significantly between the oxybutynin and observation groups., Conclusions: Oxybutynin enhances hydronephrosis improvement and vesicoureteral reflux resolution following primary endoscopic valve ablation in infants but periodic monitoring is warranted.

Objectives: Lower urinary tract abnormalities have been considered to be contraindications for renal transplant. However, advancements in diagnosis and treatment in this area have allowed renal transplant as a treatment choice in selected cases. We evaluated clinical outcomes of pediatric renal transplant in patients with lower urinary tract dysfunction., Materials and Methods: We retrospectively evaluated data from 165 pediatric renal transplant patients, and data were compared between patients with and without lower urinary tract dysfunction. Patient demographics, cause of chronic renal failure, acute rejection episodes, and graft loss were included in our analyses., Results: Seventeen patients had lower urinary tract dysfunction, and the remaining 148 patients had functional lower urinary tracts. Patients with lower urinary tract dysfunction were younger than the other patient group at diagnosis of chronic renal failure. The mean follow-up after renal transplant in the 2 groups was similar. Differences with regard to donor type, immunosuppressive treatment, and acute rejection episodes were not significant between the 2 groups. Eight patients had lost their grafts during follow-up; however, only 1 of these patients was in the lower urinary tract dysfunction group. Graft loss rate was similar between the groups., Conclusions: Pediatric patients with lower urinary tract dysfunction had similar graft outcomes versus other pediatric renal transplant patients. Careful evaluation and preparation of the lower urinary tract are important factors for renal transplant success.

Background: Primary vesicoureteral reflux (VUR) is the most common urological anomaly in children. Voiding cystourethrography (VCUG) is considered the reference standard for the diagnosis of VUR. Even if it is a secure and standardized technique, it is still an invasive method, hence, the effort to find an alternative method to diagnose VUR. The aim of the study is to evaluate the diagnostic accuracy of 99m TC-MAG3 scintigraphy with indirect cystography in detecting VUR and to estimate any interobserver variability in 99m TC-MAG3 scintigraphy interpretation., Methods: The authors retrospectively reviewed all the pediatric patients who underwent both a VCUG and a 99m TC-MAG3 renal scintigraphy at the study institution between 2012 and 2016., Results: A total of 86 children (and 168 renal units) were included. MAG3 scan revealed a sensitivity of 54% and a specificity of 90% with positive predictive value of 79% and negative predictive value of 73%. Each MAG3 scintigraphy was then independently and blindly evaluated by a pediatric urologist and two nuclear physicians. After revision, the concordance between VCUG and MAG3 in reflux cases dropped from 54% to 27% (on average), and the reviewers reclassified most examinations as non-conclusive., Conclusions: 99m TC-MAG3 renal scintigraphy with indirect cystography showed low sensitivity in detecting VUR of any grade and cannot, therefore, be proposed as completely alternative to VCUG in the diagnosis of VUR. Moreover, MAG3 scintigraphy interpretation for the diagnosis of VUR has a very high interobserver variability, mostly because of the lack of a correct and complete voiding phase., (Copyright © 2019 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Objective: The objective of the study was to evaluate the predictive value of distal ureteral diameter ratio (UDR) on outcome of primary vesicoureteral reflux (VUR) and reflux resolution after endoscopic injection., Patients and Methods: Three hundred eighty-three patients treated for primary VUR between January 2010 and October 2015 were retrospectively reviewed. The parameters analyzed were age at diagnosis, sex, grade and lateralite of VUR, complaints at admission (febrile urinary tract infection, antenatal hydronephrosis, family history),bladder-bowel dysfunction (urgency, incontinence, constipation), dimercaptosuccinic acid (DMSA) scintigraphy findings, follow-up period, clinical course (spontaneous resolution or surgical correction), time of spontaneous resolution, surgical treatment time and age, materials used for injection and success of endoscopic injection. Ureteral diameter ratio was calculated on the initial VCUG at the time of the diagnosis as the largest ureteral diameter within the false pelvis divided by the distance between L1-L3.The correlation between UDR, clinical outcome (spontaneous resolution/surgical correction) and success of endoscopic injection was evaluated by logistic regression analysis. To compare the effect of UDR and grade of reflux on spontaneous resolution, multivariate logistic regression analysis was performed in three models together with sex, age, resolution time, presence of febrile UTI and DMSA scan findings., Results: Three hundred eighty-three patients were enrolled. There was a strong correlation between UDR and grade of reflux (p < 0,0001). Ureteral diameter ratio was higher in patients whose complaints at admission were family history and febrile UTI, but this correlation was not statistically significant (p > 0.05). When the correlation between UDR and the DMSA scan findings was evaluated, UDR was found to be significantly higher in patients with moderate and severe scarring. Bladder-bowel dysfunction was present in 111 patients (28.9%). There was no significant correlation between BBD and UDR (p > 0.05). 62 patients showed spontaneous resolution in a median duration of 1.55 years. The predictive value of UDR for spontaneous resolution was more significant than grade (p < 0.001).There was no spontaneous resolution in patients with UDR over 0.45.321 patients underwent operation (248 endoscopic injection, 17 ureteroneocystostomy, 56 endoscopic injection+ureteroneocystostomy). When the predictive value of the reflux grade and UDR in the success rate of endoscopic correction was compared, UDR was shown to be significantly more predictive than the grade of reflux (p < 0.05). Ureteral diameter ratio was significantly higher in patients whose injection treatment was unsuccessful. Each 0.05 unit increase in UDR affected the success of endoscopic injection negatively (95% CI:<0.001-0.071)., Conclusion: Ureteral diameter ratio is an objective measurement of VUR and appears to be a new predictive tool for clinical outcome and success after endoscopic injection., (Copyright © 2019 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Objectives: To evaluate the clinical spectrum and patterns of clinical presentation in congenital anomalies of kidney and urinary tract., Methods: We enrolled 307 consecutively presenting children with congenital anomalies of kidney and urinary tract at the pediatric nephrology clinic. Patients were evaluated clinically, with serum biochemistry, appropriate imaging and radionuclide scans., Results: The most common anomaly was primary vesicoureteric reflux (VUR) (87, 27.3%), followed by pelviureteral junction obstruction (PUJO) (62,20.1%), multicystic dysplastic kidney (51 16.6%), non-obstructive hydronephrosis (32, 10.4%) and posterior urethral valves (PUV) (23, 7.4%). 247 (80.4%) anomalies had been identified during the antenatal period. Another 33 (10.7%) were diagnosed during evaluation of urinary tract infection, and 21 (6.8%) during evaluation for hypertension at presentation. Obstructive anomalies presented earlier than non-obstructive (7 (3, 22.5) vs 10 (4, 24) mo: (P=0.01)). The median (IQR) ages of presentation for children with PUV (n=23), VUR (n=87) and PUJO (n=62) were 4 (2, 14) mo, 10 (5, 27) mo, and 7 (3, 22.5) mo, respectively. Nine (2.9%) children had extrarenal manifestations., Conclusions: The median age at clinical presentation for various subgroups of anomalies indicates delayed referral. We emphasize the need for prompt referral in order to initiate appropriate therapeutic strategies in children with congenital anomalies of kidney and urinary tract.

Objective: To analyze factors influencing reflux resolution in patients with the coexistence of non-neurogenic lower urinary tract dysfunction and vesicoureteral reflux., Methods: The data of 153 children who were diagnosed with vesicoureteral reflux and accompanying non-neurogenic lower urinary tract dysfunction between 2010 and 2015 were retrospectively evaluated. Patients with neurogenic and anatomical malformations, monosymptomatic nocturnal enuresis, previous history of vesicoureteral reflux surgery, irregular and/or incomplete follow-up data were excluded. After exclusion of 55 patients, 98 patients were enrolled in this study. Patients were divided into two groups according to the presence of spontaneous vesicoureteral reflux resolution during the follow-up period. Group 1 consisted of 54 children with spontaneous vesicoureteral reflux resolution, whereas group 2 included 44 children without resolution. Medical history, physical examination, urinalysis, uroflowmetry combined with electromyography, ultrasonography, as well as the Dysfunctional Voiding and Incontinence Symptom Score questionnaire were also evaluated., Results: The mean age at presentation was 7.57 ± 0.23 years (range 5-13 years), and the mean follow-up period was 28.3 months. Significant differences were noted between the two groups in terms of dysfunctional voiding and incontinence symptom score, bladder wall thickness, and the post-void residual urine volumes. In addition, lower urinary tract symptoms, namely frequency, urgency and daytime incontinence, were found to be higher in group 2. In multivariate analysis, post-void residual urine volume and Dysfunctional Voiding and Incontinence Symptom Score were found to affect reflux resolution rates (P = 0.002, P = 0.002, respectively)., Conclusions: The absence of significant post-void residual urine volume, and a low Dysfunctional Voiding and Incontinence Symptom Score increase the likelihood of spontaneous resolution rates of vesicoureteral reflux in children with non-neurogenic lower urinary tract dysfunction., (© 2019 The Japanese Urological Association.)

Background: A bilateral duplex collecting system is an unusual renal tract abnormality. Vesicoureteral reflux may be associated. We describe a rare case of bilateral duplex collecting system with bilateral vesicoureteral reflux in which the refluxing ureter on the left side drains the upper pole moiety contrary to what is often found., Case Presentation: A 24-year-old married Arab woman presented with ascending left-sided flank pain during micturition. She complained of recurrent urinary tract infections. A physical examination and laboratory tests were normal. Voiding cystourethrography and computed tomography scan detected bilateral duplex collecting system, grade IV vesicoureteral reflux on the left side, and grade I vesicoureteral reflux on the right. She underwent left heminephrectomy and dextranomer/hyaluronic acid injections on the right side. After a year of follow-up, a clinical examination and imaging findings were unremarkable., Conclusions: A bilateral duplex collecting system with refluxing upper pole moiety ureter is a very rare entity. The diagnosis should be suspected when exploring any flank pain with recurrent urinary tract infections to avoid subsequent renal impairment. Furthermore, this case shows how some common symptoms may lead to finding an unexpected urinary tract abnormality.

Objectives: To assess the diagnostic performance of urinary dysfunction patterns associated with vesicoureteral reflux (VUR) in children over the age of 3 according to the result of the first endoscopic treatment (ENDT1), grouped into a classification designed by our group (CMD.URI-La Fe). Comparison with other current classifications such as that of Van Batavia et al. MATERIAL AND METHODS: Ambispective cross-cutting study of a sample of 50 children., Exclusion Criteria: previous ENDT, age ≤ 3 years, anatomical or neurological anomalies and a history of ureteral or abdominopelvic surgery. Prior to the ENDT1, a bladder voiding function assessment by uroflowmetry+electromyography (UF-EMG) and post-mictional residue (ultrasound). Other variables from the bladder diary, pre-mictional bladder wall thickness and other clinical variables. The correction of VUR was assessed by isotope cystography 3 months after the treatment. Urinary patterns were classified according to the significant variables (URI-La Fe), and the diagnostic performance of this classification was assessed, comparing it to the classification of patients as proposed by Van Batavia et al. RESULTS: Mean age: 6.8±2.28 years. Males/females (44%/56%). Grades of VUR (mild/moderate/severe). ENDT1 VUR correction rate: 77% (n=38). Diagnostic performance (Van Batavia; URI-La Fe): correct prediction (37.5%; 75%), sensitivity (32.4%; 87.8%), specificity (54.5%; 46.6%), positive predictive value (70.6; 78.3%) and negative predictive value (19.4%; 63.6%)., Conclusions: Our results show the usefulness of the non-invasive test and the classification of urinary dysfunction in children aged over 3 years prior to the first endoscopic treatment of VUR., (Copyright © 2018 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.)

Objectives: To evaluate the first 100 cases of in utero myelomeningocoele (MMC) repair and urological outcomes in a prospective analysis aiming to define possible improvement in bladder function., Patients and Methods: We used a protocol consisting of a detailed medical history, urinary tract ultrasonography, voiding cystourethrography, and urodynamic evaluation. Patients were categorised into four groups: normal, high risk (overactive bladder with a detrusor leak-point pressure >40 cm H 2 O and high filling pressures also >40 cm H 2 O), incontinent, and underactivity (underactive bladder with post-void residual urine), and patients were treated accordingly., Results: We evaluated 100 patients, at a mean age of 5.8 months (median 4 months), classified as high risk in 52.6%, incontinent in 27.4%, with underactive bladder in 4.2%, and only 14.7% had a normal bladder profile. Clean intermittent catheterisation was initiated in 57.3% of the patients and anticholinergics in 52.6%. Antibiotic prophylaxis was initiated in 19.1% of the patients presenting with vesico-ureteric reflux., Conclusion: The high incidence of abnormal bladder patterns suggests little benefit of in utero MMC surgery concerning the urinary tract., (© 2018 The Authors BJU International © 2018 BJU International.)

Vesicoureteral reflux, retrograde flow of urine from the bladder into the upper urinary tract, is one of the most common urological diagnoses in the pediatric population. Diagnosis and subsequent management of urinary reflux have become increasingly debated in the past decade, with divergent opinions over which patients should be evaluated for reflux, and when detected, which children should receive intervention. Although some argue that vesicoureteral reflux is a "phenotype" that often resolves without intervention, others contest that untreated reflux has the potential to cause irreversible renal damage over time. Voiding cystourethrogram images the urethra and bladder during both bladder filling and emptying, as well as the ureters and kidneys when reflux is present, and is considered the gold standard for diagnosing vesicoureteral reflux. Once detected, therapeutic options for urinary reflux are diverse, ranging from observation with or without low-dose antibiotic prophylaxis to a variety of operative interventions. Management should be based on a multitude of factors including patient age, risk of subsequent urinary tract infections, risk of renal parenchymal injury, a given child's projected clinical course and parental preference. Over the past two decades, investigators have elucidated many crucial voiding cystourethrogram findings in addition to grade that provide significant prognostic information and are useful in determining the best course of action for a child on a more individualized basis., (© 2019 The Japanese Urological Association.)

Purpose: Ureteral complications following renal transplantation are more common in children than in adults. We identify potential risk factors for ureteral complications in pediatric patients., Materials and Methods: We retrospectively studied a cohort of patients who underwent renal transplantation at Lurie Children's Hospital between 2004 and 2016. We analyzed the associations between patient characteristics, operative factors, graft characteristics and postoperative complications., Results: A total of 224 renal transplantations in 219 patients were identified. Preexisting bladder pathology was present in 25% of cases. Overall rate of ureteral complications was 16%, with symptomatic vesicoureteral reflux being the most common. Ureteral complications were seen significantly more frequently in patients with underlying bladder pathology (26% vs 12%, p = 0.01). Rate of postoperative vesicoureteral reflux in patients with bladder pathology was lower when a urologist performed the reimplantation but the difference was not statistically significant (15% vs 27%, p = 0.35). Urologists were significantly more likely to perform the ureteral anastomosis in patients on clean intermittent catheterization (85% vs 43%, p = 0.004) and in patients with a history of complex bladder reconstruction (75% vs 28%, p <0.001)., Conclusions: Patients with existing bladder pathology are at increased risk for ureteral complications, particularly vesicoureteral reflux. Since pediatric urologists routinely perform ureteral reimplantation in patients with existing bladder pathology, these patients may benefit from a multidisciplinary approach between urology and transplant surgery at renal transplantation.

Congenital anomalies of the kidney and urinary tract (CAKUT) are a wide range of congenital structural renal defects. CAKUT is the leading cause of chronic renal failure and end-stage renal disease in children. Studies in humans and animal models have confirmed the large genetic contribution to CAKUT. The previous evidence suggested that human TBX6 coding mutations might cause CAKUT via gene-dosage insufficiency. However, the potential involvement of TBX6 noncoding mutations in CAKUT remains to be elucidated. Here, we described DNA sequencing and copy-number analysis of TBX6 in 269 Chinese subjects with CAKUT. Interestingly, we identified two heterozygous noncoding variants of TBX6 in sporadic subjects with CAKUT: one is c.769-7delT, from a subject with duplex renal and collecting system, and the other is a 3' untranslated region (3'-UTR) variant (c.1392C>T) from a subject with unilateral renal hypoplasia. These two TBX6 noncoding variants are novel and extremely rare, respectively, in human populations archived in the ExAC database. The mini-gene splicing assay showed that the TBX6 c.769-7delT variant significantly reduced the splicing efficiency of TBX6 intron 5 when compared to the wild-type control. In this work, we identified a novel splicing variant of TBX6 in human CAKUT. Our experimental observations suggested that the TBX6 noncoding variant can affect gene expression and may potentially be involved in human CAKUT.

Background: The purpose of this study was to resolve the clinical question as to whether all patients with unilateral multicystic dysplastic kidney (MCDK) should receive voiding cystourethrography (VCUG)., Methods: This is a retrospective study using cross-sectional analysis. Seventy-five children with unilateral MCDK were enrolled, excluding patients with other genetic or chromosome abnormalities, spinal cord diseases, or anal atresia. We reviewed their records from medical charts and calculated risk factors for abnormal VCUG using multivariate logistic regression analysis., Results: Abnormal VCUG findings were present in 24 of 75 patients (32.0%), specifically, vesicoureteral reflux (VUR) in 8 (10.6%), including high-grade VUR in 2 (2.7%), and only lower urinary tract or bladder disease in 16 (21.3%). In multivariate analysis, only abnormal findings by ultrasonography was an independent risk factor for abnormal VCUG findings with statistical significance in multivariate analysis (OR 6.57; 95% CI 1.99-26.26; P = 0.002). When we excluded five patients who showed similar findings by ultrasonography and VCUG, abnormal findings by ultrasonography were again calculated as an independent risk factor (OR 4.44; 95% CI 1.26-28.42; P = 0.02). Sensitivity, specificity, positive predictive value, and negative predictive value of abnormal findings by ultrasonography to predict urologic anomalies by VCUG in these children were 83%, 59%, 49%, and 88%, respectively. Two children required a third ultrasonography to detect abnormal findings., Conclusions: We can select, using only abnormal findings by ultrasonography, children with unilateral MCDK who should undergo VCUG. We would also like to emphasize that ultrasonography should be performed repeatedly to detect congenital anomalies of the urinary tract.

Objective: To determine whether vesicoureteral reflux (VUR) that occurs during either the filling or voiding phase on voiding cystourethrogram (VCUG) has prognostic significance on successful endoscopic treatment., Materials and Methods: A retrospective review was performed of 299 patients (438 ureters) with VUR who underwent endoscopic treatment with dextranomer/hyaluronic acid copolymer (Deflux) at a single institution from 2010 to 2013. Success was defined as absence of VUR on 3-month follow-up VCUG. Preoperative VCUGs were analyzed to determine whether the onset of VUR occurred during the filling or voiding phase. Predictor variables to determine success were analyzed, with a specific focus on VUR timing., Results: Success rate was 319/438 (72.8%) by ureter and 202/299 (67.6%) by patient. Reflux was seen during the filling and voiding phases in 290 and 148 ureters, respectively. Success rate was 203/290 (78%) for filling VUR and 116/148 (70%) for voiding VUR. Univariable analysis revealed voiding VUR had significantly increased odds of success (odds ratio [OR] 3.2, P = .049), while high-grade reflux (OR 0.53, P = .005) had significantly decreased odds of success. Multivariable analysis showed that voiding VUR (OR 3.2, P = .005) had significantly higher odds of success while those with high grade reflux (OR 0.42, P = .017) had significantly decreased odds of success., Conclusion: The timing of VUR on preoperative VCUG appears to be an important independent predictor of successful endoscopic treatment of VUR. This has important clinical considerations when selecting VUR patients who would be best candidates for endoscopic treatment., (Copyright © 2018. Published by Elsevier Inc.)

Background: Reflux nephropathy is a common urinary tract malformation, and a substantial cause of morbidity in women of childbearing age. While recent studies provide further new information on pregnancy-related outcomes, their results are heterogeneous and a systematic meta-analysis may help the interpretation. The aim of this review was to analyze pregnancy-related outcomes in the recent literature on reflux nephropathy (2000-2016), to perfect the estimation of risks, and to identify specific research needs., Methods: We searched Medline, EMBASE and the Cochrane review databases for the period 2000-2016 (PROSPERO registration no. 42016042713)., Selection Criteria: all case series and case reports dealing with reflux nephropathy and reporting on at least one pregnancy outcome. Data were extracted from eligible case series (≥ 6 cases). For the outcomes preeclampsia (PE), pregnancy-induced hypertension (PIH), preterm birth, and newborns small for gestational age, we employed as a control group the low-risk pregnancies from a multicenter database including 1418 live-born singletons. Case reports were analyzed narratively., Results: The search retrieved 2507 papers, of which 7 case series and 4 case reports were retained. The series report on 434 women with 879 pregnancies; no study reported controls. Compared to the low-risk controls, the meta-analysis showed an increased risk of PIH (odds ratio, OR 5.55; confidence interval, CI 3.56-8.66), PE (OR 6.04; CI 2.41-15.13), and all hypertensive disorders combined (OR 10.43; CI 6.90-15.75). No difference was observed in preterm delivery and caesarean sections. A higher incidence of stillbirth was reported in one paper. Conversely, the 4 case reports (on 10 pregnancies) alert us to a potentially severe complication, hydro(uretero)nephrosis with or without infection., Conclusion: Reflux nephropathy is associated with an increased risk of PIH and PE, but not of preterm delivery, suggesting the occurrence of late 'maternal' PE. The finding of a higher incidence of stillbirths in one series requires further analysis. Strict follow-up of these women is needed, in particular in late pregnancy stages, to avoid and manage in particular hypertensive pregnancy complications.

Objective: To determine the different urine flow patterns and active pelvic floor electromyography (EMG) during voiding in children with vesicoureteral reflux (VUR) as well as presenting the prevalence of lower urinary tract symptoms in these patients., Materials and Methods: We retrospectively reviewed the charts of children diagnosed with VUR after toilet training from Sep 2013 to Jan 2016. 225 anatomically and neurologically normal children were included. The reflux was diagnosed with voiding cystourethrography. The study was comprised an interview by means of a symptom questionnaire, a voiding diary, uroflowmetry with EMG and kidney and bladder ultrasounds. Urine flow patterns were classified as bell shape, staccato, interrupted, tower and plateau based on the current International Children's Continence Society guidelines., Results: Of 225 children with VUR (175 girls, 50 boys), underwent uroflowmetry + EMG, 151 (67.1%) had an abnormal urine flow pattern. An active pelvic floor EMG during voiding was confirmed in 113 (50.2%) children. The flow patterns were staccato in 76 (33.7 %), interrupted in 41 (18.2%), Plateau in 26 (11.5%), tower in 12 (5.3%) and a bell shape or normal pattern in 70 (31.5%). Urinary tract infection, enuresis and constipation respectively, were more frequent symptoms in these patients., Conclusions: Bladder/bowel dysfunction is common in patients with VUR that increases the risk of breakthrough urinary tract infections in children receiving antibiotic prophylaxis and reduces the success rate for endoscopic injection therapy. Therefore investigation of voiding dysfunction with primary assessment tools can be used prior to treating VUR., Competing Interests: Conflict of interest: None declared., (Copyright® by the International Brazilian Journal of Urology.)

Introduction: The objective of this research was to determine whether vesicoureteral reflux(VUR) was associated with evolution to renal scarring (RS) following a febrile urinary tract infection (UTI) in infants., Materials and Methods: Our research included 100 infants, ages up to 1 year with a first febrile UTI. The diagnostic was based on results of: laboratory findings, ultrasonography (USG), voiding cystourethrography (VCUG) and initial and control renal scintigraphy (DMSA renal scan) withtechnetium 99m Tcsuccimer (dimercaptosuccinic acid), to assess the acute pyelonephritis (APN), VUR and RS., Results: APN was proven with DMSA renal scan in 66 (66%) infants. Twenty-two infants (33.3%) had VUR in-group of patients with APN. On the control DMSA scan, performed 6 months after the first DMSA, the presence of RS was found in 18 (27.27%) infants. In infants with renal scars VUR were discovered in 9 of them (50%)., Conclusions: The pathogenesis of RS after febrile UTI in young children is multifactorial. Children with VUR have an increased risk for APN and RS. However, VUR is not the only precondition for RS. Creating a renal scarring cannot be imagined without the inflammatory process of the upper urinary system. Therefore, early detection and treatment of febrile UTIs in children and identify children at risk for RS are of primary importance.

Vesicoureteric reflux (VUR) is the most common congenital anomaly of the urinary tract that occurs in 30%-50% of children presenting with recurrent urinary tract infections. Long-standing untreated VUR results in renal scarring and hydronephrotic changes ultimately leading to chronic renal failure and arterial hypertension. However, it may also result in diffuse tubulopathy compromising the concentrating capacity of tubules and urinary acidification defects. Renal tubular dysfunction should be considered in all children with VUR presenting with failure to thrive, rickets, bony deformity/pain, hypokalemia, and metabolic acidosis. We report such a case of a 16-year-old male adolescent who presented with rickets, failure to gain weight and height, bony pains, and muscle weakness with a history of VUR. On investigation, he was found to have normal anion gap metabolic acidosis with hypokalemia suggestive of distal renal tubular acidosis. He responded well to oral alkali and potassium replacement therapy., Competing Interests: None declared.

Introduction: The long-held belief that a ureteral re-implant tunnel should be five times the diameter of the ureter, as proposed by Paquin in 1959, ignores the effect of the orifice on the occurrence of reflux. In 1969, Lyon proposed that the shape of the ureteral orifice (UO) is more important than the intravesical tunnel. However, both theories missed quantitative evidence from principles of physics. The goal of the current study was to test Lyon's theory through numerical models (i.e. to quantify the sensitivity of ureterovesical junction (UVJ) competence to intravesical tunnel length and to the UO)., Materials and Methods: The closure of a three-dimensional spatial configuration of ureter, constrained within a bladder, was simulated. Two common UO shapes (i.e. golf type vs 2-mm volcano type (Summary Fig.)), and two different intravesical ureteral tunnel length/diameter ratios (3:1 and 5:1) were examined. The required closure pressures were then compared., Results: The UO was a significant factor in determining closure pressure. Given the same intravesical ureteral tunnel length/diameter ratio, the required closure pressure for the volcanic orifice was 78% less than that for the golf orifice. On the other hand, the intravesical ureteral tunnel length/diameter ratio had minimal effect on the required closure pressure. As the intravesical ureteral tunnel length/diameter ratio changed from 3:1 to 5:1, the required closure pressure was reduced by less than 7%, regardless of the orifice shape., Conclusions: The simulation results showed that UVJ competence was more sensitive to a 2-mm protrusion of the UO compared to an increase in the intravesical tunnel length from 3:1 to 5:1. This agrees with Lyon's theory, and at the same time challenges Paquin's 5:1 rule. Researchers could use this information to consider the UO configuration in further animal, human, computer or material models., (Copyright © 2018 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Introduction: Asymptomatic post-renal transplant reflux is common but only 5-10% patients are diagnosed with vesico-ureteral reflux in the setting of post-transplant febrile urinary tract infections, requiring redo ureteroneocystostomy (redo-UNC). Here we report the renal function outcomes of 37 such patients, stratified by lower urinary tract (LUT) status., Objective: We hypothesized that those with pre-transplant LUT dysfunction would have lower glomerular filtration rate (GFR) on follow-up., Study Design: Using procedure codes, 37 patients who underwent renal transplant followed by redo-UNC for transplant reflux at our institution between 1991 and 2014 were identified. Patient characteristics and GFR levels from four different time points were recorded. Comparisons were made between those with and without LUT dysfunction, using Fisher's exact, Wilcoxon rank sum, or signed-rank tests. Generalized estimating equations were constructed to account for the clustered nature of GFR within each LUT group and to assess their change over time., Results: Twelve patients (32%) had pre-transplant LUT dysfunction. The proportion of males in this group was significantly higher (75% vs. 32%, p = 0.032), and there was no statistical difference towards presenting earlier with post-transplant reflux (1.4 vs. 2.3 years, p = 0.087). After an average of 4.9 years, the median GFRs were similar between the two groups (53 mg/dL vs. 58 mg/dL, p = 0.936). There was no significant difference in GFR at this last follow-up time point in patients with and without LUT dysfunction., Discussion: Vesicoureteral reflux in the setting of renal transplantation is common and doesn't often require repair. In our series, we found that those with LUT dysfunction did not present statistically sooner with symptomatic transplant reflux. Longer-term follow-up did show a decline in GFR but did not reveal a difference in GFR in patients' with and without LUT dysfunction., Conclusions: Pediatric post-transplant GFR after open redo ureteral reimplant decreases over time in similar fashion in patients with symptomatic reflux regardless of whether they have LUT dysfunction or normal anatomy. Vigilance should apply to the recognition, treatment, and follow-up of all symptomatic transplant reflux regardless of LUT status., (Copyright © 2018 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Objective: To assess whether antibiotic reduces voiding cystourethrogram (VCUG)-associated urinary tract infection (UTI)., Design: Open-labelled randomised controlled trial., Setting: Tertiary paediatric nephrology centre., Patients: 120 children (age 2 months-5 years) undergoing VCUG., Interventions: Children were randomised into group A (antibiotic, n=72) or group B (no antibiotic, n=48) in 3:2 ratio. Group A received oral antibiotic (cephalexin if <6 months or co-trimoxazole if >6 months old) a day prior to VCUG and continued for 1 day post VCUG., Main Outcome Measures: The main outcome measure is incidence of VCUG-associated UTI. Urine was checked on day 3 after VCUG and UTI was defined as significant growth of a single organism in a symptomatic child., Results: The median age was 8 months (IQR 13 months) with 68% male. Indication for undertaking VCUG was history of UTI (first UTI in infancy=43, recurrent UTI=49) and congenital anomaly of kidney and urinary tract without any UTI (n=28). Post-VCUG UTI was significantly higher among group B in comparison to group A (17% (n=8) vs 1.4% (n=1); p=0.01, OR=14.2 (95% CI 1.7 to 117)). Multivariate binary logistic regression analysis found an abnormal pre-VCUG ultrasound scan to be a significant independent risk factor for post-VCUG UTI (p=0.02, OR=9.51, 95% CI 1.43 to 63.4). The number needed to treat with antibiotic to prevent one post-VCUG UTI was 6.5, which reduced to 4 if only the group with abnormal pre-VCUG ultrasound scan was included., Conclusions: Antibiotic significantly reduces post-VCUG-acquired UTI especially in those with abnormal ultrasound scans., Trial Registration Number: Clinical Trial Registry of India: CTRI/2017/03/00824., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Two common abnormalities in ureters include primary refluxing megaureter (PRM) and primary obstructed megaureter (POM). The aim of this study was to represent the numerical simulation of the urine flow at the end of the ureter with vesicoureteral reflux (VUR) and POM during peristalsis. Methodologically, the peristalsis in the ureter wall was created using Gaussian distribution. Fluid-structure interaction (FSI) was applied to simulate urine-elastic wall interactions; and governing equations were solved using the arbitrary Lagrangian-Eulerian method. Theories such as wall elasticity, Newtonian fluid, and incompressible Navier-Stokes equations were used. Velocity fields, viscous stresses and volumetric outflow rate profiles were obtained through the simulation of the ureter with VUR and POM during peristalsis. In addition, the effect of urine viscosity on flow rate was investigated. When the bladder pressure increased, VUR occurred because of the ureterovesical junction (UVJ) dysfunction, leading to high stresses on the wall. In the POM, the outflow rate was ultimately zero, and stresses on the wall were severe in the obstructed section. Comparing the results demonstrated that the peristalsis leads to even further dilation of the prestenosis portion. It was also observed that the reflux occurs in the ureter with VUR when the bladder pressure is high. Additionally, the urine velocity during the peristalsis was higher than the non-peristaltic ureter.

Background: Albuminuria is a potential biomarker of chronic kidney disease (CKD) in various glomerular diseases. Vesicoureteral reflux (VUR) often progresses to CKD, and study is required of use of albuminuria as a biomarker for this condition. The aim of this study was to evaluate the association between albuminuria and glomerular filtration rate (GFR) or filtration fraction (FF) in children with VUR., Study Design: In this retrospective study, renal parameters of 141 children with VUR were investigated, using inulin clearance, FF, and albuminuria. The association between urinary albumin to creatinine ratio (ACR), GFR, and FF was analyzed in a continuous manner by calculating the β coefficient, and also in a binary manner by calculating the OR., Results: Using both continuous and binary analyses, ACR values were negatively and significantly associated to GFR values in patients with low, normal, or high FF values (Table). It was also positively and significantly associated with FF values in patients with low, normal or high GFR values (Table). No association was found between ACR and gender, VUR stages or laterality, number of urinary tract infection, presence of a single functional kidney, history of reflux surgery, or renal scars or hypertension., Discussion: ACR is associated with CKD in patients with VUR. In addition, increased urinary albumin excretion cannot be completely and solely explained by decreased GFR and/or increased FF values. The two main limitations of this study are the crude assessment of renal scarring, which prevented finer analysis between albuminuria and renal scarring surface area, and that the study cohort may not be representative of the true VUR population., Conclusion: This study shows that albuminuria is associated with decreased renal function in patients with VUR and that it could be used to monitor renal function in this condition., (Copyright © 2017 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Aims: To evaluate the effectiveness and reliability of onabotulinum toxin A (onaBoNT-A) injections in pediatric patients with non-neurogenic detrusor overactivity (NNDO)., Methods: Between January 2010 and February 2016, 39 patients underwent onaBoNT-A injections for NNDO, and were evaluated retrospectively. Three-day voiding diary was filled at baseline, and at the postoperative 9th month. The voiding frequency, incontinence episodes, and the cystometric capacity were noted. Vesicoureteral reflux (VUR) associated with NNDO, and presence of nocturia were recorded. Additional injection requirements were also stated., Results: We reached the data of 33 patients on 9th month. The mean age was determined as 8.75 ± 3.01 (5-16) years. Initially, the mean bladder capacity was calculated as 114.66 ± 35.23 mL on the voiding diary, and 153.15 ± 47.40 mL on the baseline urodynamic study. After the procedures, the mean bladder capacity increased to 140.84 ± 45.61 mL (P = 0.0011), the mean daily voiding frequency decreased from 10.36 ± 1.05 to 7.42 ± 0.83 (P = 0.01), and the mean incontinence episodes decreased from 2.72 ± 1.87 to 1.18 ± 1.13 (P = 0.001), on voiding diary. VUR associated with NNDO was determined in 10 (30.3%) patients. The degree of VUR decreased three in patients, and VUR disappeared in five patients following the injections (P = 0.011). Fourteen (42.4%) patients had nocturia, and after the injections, nocturia disappeared in five (15.15%) patients (P = 0.151). Additional injections were required in 10 (30.3%) patients at the 9th month., Conclusions: OnaBoNT-A injections can be used in the pediatric patients with NNDO as an effective and reliable procedure by decreasing voiding frequency, incontinence episodes, and increasing bladder capacity, with negligible side effects and complications., (© 2017 Wiley Periodicals, Inc.)

Vesicoureteral reflux (VUR) is the most common type of obstructive uropathy in children. Reflux nephropathy (RN) is one of the most common complications of VUR that inevitably leads to chronic kidney disease. Patients with end-stage kidney disease require costly treatment, and the only way to cure them is kidney transplantation. A timely institution of renoprotective therapy is a key factor helping to preserve the function of the native kidneys. Hence, it is necessary to devise new highly sensitive and minimally invasive methods for early diagnosis of RN. The purpose of this article is to review the molecular mechanisms of initiation and progression of kidney fibrosis and the opportunities of instrumental and non-instrumental methods for its diagnosis. Special attention is paid to highly specific and highly sensitive non-invasive methods for the detection of minimal changes in the renal parenchyma. The authors discuss the promising biomarkers for the diagnosis and prediction of RN.

Introduction and Objective: Management of vesicoureteral reflux (VUR) remains controversial, and reflux grade constitutes an important prognostic factor. Recent work has suggested that distal ureteral diameter ratio (UDR) is a predictive factor relative to clinical outcome independent of grade. Previous studies have noted significant inter-rater variability with grading of VUR. The present study compared inter-rater reliability of reflux grade and UDR in children with primary VUR., Study Design: Four pediatric urologists independently reviewed, in a blinded fashion, voiding cystourethrograms. For each renal unit, grade was assigned according to the standardized international scale. The UDR was calculated by dividing the largest ureteral diameter within the false pelvis by the distance between L1-L3 vertebral bodies. Correlation within each rater was determined using Pearson's correlation coefficient. Reliability of VUR grade and UDR were calculated using two-way ANOVA model inter-rater agreement., Results: Four independent raters reliably measured VUR grade (ICC = 0.87, 95% CI = 0.78-0.93) and UDR (ICC = 0.95, 95% CI = 0.92-0.97). While UDR and grade were equally reliable measures, UDR had a tighter confidence interval. For each rater, grade and UDR were well correlated (r = 0.73-0.84; P < 0.0001). For higher-grade reflux, grade was more variable than UDR (Summary Figure). Using empirical thresholds, the increased variability of grade compared with UDR may lead to significant differences in clinical decision-making among physicians (P = 0.022)., Discussion: Known discordance with grading reflux emphasizes the need for a more objective VUR measurement, as clinicians and parents often opt for clinical intervention based on both clinical course and the likelihood of spontaneous resolution. While ICC for UDR and grade were not significantly different, the confidence intervals for grade were wider due to greater variability among grade measurements. This suggests that using UDR measurements may lead to more accurate characterization of VUR and ultimately more consistent clinical decision-making across providers., Conclusions: Ureteral diameter ratio has good inter-rater reliability among pediatric urologists, with less clinically relevant variability than VUR grade. Ureteral diameter ratio is a more objective and reliable measure than grade, and may be more useful in clinical decision-making., (Copyright © 2016 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Introduction: It has been suggested that infants with high-grade vesicoureteral reflux (VUR) have lower urinary tract dysfunction (LUTD) that is characterised by large bladder capacity (BC) and increased post-void residual (PVR). However, most of these infants have normal or small BC in early infancy and develop large capacity during the first year of life., Objective: This study aimed to see whether LUTD development during the infant years in children with high-grade VUR could be prevented by early reflux resolution., Materials and Methods: For early VUR intervention, endoscopic treatment (ET) was used in a randomised trial comprising 77 infants (55 boys) aged <8 months with VUR grade 4-5 (n = 30/n = 47); 39 were randomised to antibiotic prophylaxis and 38 to ET. Voiding cystourethrogram, free voiding observation (FVO) and renal scintigraphy were performed at baseline and after 1 year. Bladder capacity and PVR were obtained from FVO. LUTD was defined as a BC of ≥150% of expected and a PVR of ≥20 ml., Results: There were no differences in bladder function variables seen between the treatment groups, despite significant differences in VUR resolution. Analysing bladder function related to VUR outcome (VUR grade ≤2 vs grade >2), independent of treatment, showed that VUR grade ≤2 was associated with a smaller BC at 1 year (P = 0.050) (a tendency already seen at baseline) and a lower PVR at baseline (P = 0.010). PVR increased from baseline to 1 year (P = 0.037) in children with grade ≤2 VUR (Summary Table). The group with persistent bilateral grade 5 VUR at 1 year had more abnormal bladder variables compared with other study subjects, with a tendency of larger BC (P = 0.057), higher PVR (P = 0.0073) and more LUTD (P = 0.029) at baseline and a larger BC at 1 year (P = 0.016). In explanatory analyses, using logistic regression, a high PVR at baseline was identified as a predictor of VUR grade >2 (P = 0.046), persistent bilateral grade 5 VUR (P = 0.022), recurrent urinary tract infection (P = 0.034), and only a tendency was seen regarding new renal damage (P = 0.053)., Conclusion: There was no between-group difference seen in bladder function. In children with VUR resolution at follow-up, independent of treatment, BC decreased, whereas PVR increased. High PVR at baseline was a predictive factor for both non-resolution of high-grade VUR and recurrent urinary tract infection. The results suggest that LUTD cannot be prevented by early VUR resolution, but rather is an important prognostic factor for VUR outcome in both endoscopic and prophylactic treatment., (Copyright © 2016 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Primary vesicoureteral reflux (VUR) is a common pediatric condition due to a developmental defect in the ureterovesical junction. The prevalence of VUR among individuals with connective tissue disorders, as well as the importance of the ureter and bladder wall musculature for the anti-reflux mechanism, suggest that defects in the extracellular matrix (ECM) within the ureterovesical junction may result in VUR. This review will discuss the function of the smooth muscle and its supporting ECM microenvironment with respect to VUR, and explore the association of VUR with mutations in ECM-related genes.

Introduction: Voiding cystourethrography (VCUG) is the modality of choice to diagnose vesicoureteral reflux (VUR). Although grading of VUR is essential for prognosis and clinical decision-making, the inter-observer reliability for grading has been shown to vary substantially. The Randomized Intervention for Children with VesicoUreteral Reflux (RIVUR) trial provides a large cohort of children with VUR to better understand the reliability of VCUG findings., Objective: To determine the inter-observer consistency of the grade of VUR and other VCUG findings in a large cohort of children with VUR., Study Design: The RIVUR trial is a randomized controlled trial of antimicrobial prophylaxis in children with VUR diagnosed after UTI. Each enrollment VCUG was read by a local clinical (i.e. non-reference) radiologist, and independently by two blinded RIVUR reference radiologists. Reference radiologists' disagreements were adjudicated for trial purposes. The grade of VUR and other VCUG findings were extracted from the local clinical radiologist's report. The unit of analysis included individual ureters and individual participants. We compared the three interpretations for grading of VUR and other VCUG findings to determine the inter-observer reliability., Results: Six-hundred and two non-reference radiology reports from 90 institutions were reviewed and yielded the grade of VUR for 560 left and 524 right ureters. All three radiologists agreed on VUR grade in only 59% of ureters; two of three agreed on 39% of ureters; and all three disagreed on 2% of ureters (Table). Agreement was better (≥92%) for other VCUG findings (e.g. bladder shape "normal"). The non-reference radiologists' grade of VUR differed from the reference radiologists' adjudicated grade by exactly one grade level in 19% of ureters, and by two or more grade levels in 2.2% of ureters. When the participant was the unit of analysis, all three radiologists agreed on the grade of VUR in both ureters in just 43% of cases., Discussion: Our study shows considerable and clinically relevant variability in grading VUR by VCUG. This variability was consistent when comparing non-reference to the adjudicated reference radiologists' assessment and the reference radiologists to each other. This study was limited to children with a history of UTI and grade I-IV VUR and may not be generalizable to all children who have a VCUG., Conclusion: The considerable inter-observer variability in VUR grading has both research and clinical implications, as study design, risk stratification, and clinical decision-making rely heavily on grades of VUR., (Copyright © 2016 Journal of Pediatric Urology Company. All rights reserved.)

Introduction: High-grade vesicoureteral reflux (VUR) in children is associated with recurrent urinary tract infection (UTI) and renal damage. Breakthrough UTI despite continuous antibiotic prophylaxis (CAP) during the first years of life is a matter of concern and evokes early intervention. We investigated whether early endoscopic treatment (ET) of VUR grade 4-5 can reduce the risk of UTI recurrence and renal scarring., Materials and Methods: This prospective, randomized, controlled, multicentre, 1-year follow-up trial comprised 77 infants, <8 months of age with VUR grade 4-5 (Table) randomized to CAP (n = 39) or ET (with prophylaxis until resolution) (n = 38). Voiding cystourethrogram, ultrasound, renal scintigraphy, and free voiding observation were performed at study entry and after 1 year. Parenchymal defects were seen in 67 (87%) children at entry, 39 (34 boys, 5 girls) of them characterized as generalized. At follow-up, renal deterioration (new scars or progress in old damaged area) and symptomatic UTIs were reported., Results: There were 27 recurrent febrile UTIs in 6 (16%) children in the ET group and in 10 (26%) in the CAP group (p = 0.43), in eight (36%) girls and eight (15%) boys (p = 0.039). Successful VUR outcome (VUR 0-2) was seen in 22 (59%) in the ET and eight (21%) in the CAP group (p = 0.0014). Multiple recurrences were only seen in patients with persistent dilating reflux at follow-up (p = 0.019). Deterioration on scintigraphy was seen in eight children (9 kidneys) with no difference between treatment groups (p = 0.48) or sex (p = 0.17). Renal deterioration was associated with high bladder capacity (BC) and large residual volume (PVR) at 1 year (p = 0.0092 and p = 0.041). Six of the eight children with renal deterioration had a recurrent UTI (p = 0.0032). Seven of nine renal units with deterioration were seen in children with persistent VUR 3-5 at follow-up. Univariable logistic regression identified female sex and high PVR as positive predictors for recurrent UTI (p = 0.039 and 0.034) and high PVR tended to predict renal deterioration (p = 0.053)., Discussion: No differences between the treatment groups regarding recurrent UTI and renal deterioration could be found. Increased PVR and female sex were positive predictors for UTI recurrences. VUR grade at follow-up was correlated to UTI recurrence and renal deterioration., Conclusion: This study did not show any difference between ET and CAP in reducing the risk of UTI recurrence or renal deterioration. The rate of VUR resolution was higher in the ET group and VUR grade at follow-up correlated with both UTI recurrence and renal deterioration., (Copyright © 2017. Published by Elsevier Ltd.)

Purpose: Etiopathogenesis of VUR is composite and not fully understood. Many data indicate the importance of genetic predisposition. The aim of this study was to establish the relationship of selected polymorphisms: 14094 polymorphism of the ACE, polymorphism rs1800469 of TGFβ-1, rs5443 gene polymorphism of the GNB3 and receptor gene polymorphism rs5186 type 1 AGTR1 with the occurrence of the primary vesicoureteral reflux., Material: The study included 190 children: 90 with the primary VUR confirmed with the voiding cystourethrogram and excluded secondary VUR and a control group of 100 children without a history of the diseases of the genitourinary tract., Methods: The study was planned in the scheme: "tested case versus control." Genomic DNA was isolated from the leukocytes of peripheral blood samples. The results were statistically analyzed in the Statistica 10 using χ 2 test and analysis of the variance Anova., Results: Any of the four studied polymorphisms showed no difference in the distribution of genotypes between patients with primary vesicoureteral reflux and the control group. In patients with VUR and TT genotype polymorphism rs5443 GNB3 gene, the glomerular filtration rate was significantly higher than in patients with genotype CC or CT., Conclusions: (1) No relationship was found between the studied polymorphisms (14094 ACE gene, rs1800469 gene TGFβ1, GNB3 gene rs5443, rs5186 AGTR1 gene) and the occurrence of primary vesicoureteral reflux. (2) TT genotype polymorphism rs5443 GNB3 gene may be a protective factor for the improved renal function in patients with primary vesicoureteral reflux in patients with genotype CC or CT.

Introduction: Congenital anomalies of the kidney and urinary tract (CAKUT) represent several types of malformations with occurrence of 1 in about 500 live births., Objective: Small for gestation age (SGA) may influence in prevalence of CAKUT and progression of chronic kidney disease (CKD) in children. The aim of this study was to elaborate our experiences with detected CAKUT in a cohort of SGA born children in Macedonia., Methods: Our cohort consisted of 100 SGA born children investigated for associated congenital anomalies of urinary tract. We analyzed anthropometric and clinical birth data in children with diagnosed CAKUT and estimated the stage and time of onset of CKD by biochemical and imaging technics., Results: We revealed 7 (7.0%) SGA born children with congenital anomalies of the urinary tract. Their mean birth weight was very low 1855 gr (-3.93 SDS) and the birth length 45.57cm (-2.17 SDS), as well. A significant growth failure with reduced weight and BMI were noticed at the time of diagnosis. A diagnosis of CAKUT in 4/7 was established in the first few months of life, but in others 3 later in early childhood. Three children revealed with unilateral kidney agenesis, 2 had hypo-dysplastic kidneys and in 2 children was found vesicoureteral reflux. Normal glomerular filtration rate was estimated in 2 children with CAKUT. Stage 2 CKD with GFR 60-90 ml/minx1.73m2 had 3 children, 1 patient was graded in stage 3 and one child needed kidney transplantation, stage 5 CKD., Conclusions: We presented 7 SGA born children with CAKUT. An early recognition, assessment and treatment of these anomalies might improve their quality of life.

Objectives 'Sleeping beauties', i.e. publications that are not cited for a long while, present interesting findings in science. This study analysed the citation trends of sleeping beauties in paediatric research. Methods The study used bibliometric software to analyse the papers citing sleeping beauties in paediatric research, to understand the context in which paediatric sleeping beauties were finally cited and the impact of these sleeping beauties on paediatric research. Results Two paediatric sleeping beauties, addressing medical homes and the transition from paediatric to adult health care, respectively, awakened in response to organizational needs. Both presented novel concepts of paediatric service organization that became important because of an increased need for optimization of services. Conclusion All sleeping beauties bring new knowledge that becomes important only after several years. Paediatric sleeping beauties exhibited unique characteristics; however, their presence in paediatric research shows that knowledge acquisition in paediatrics resembles that in other disciplines.

The voiding cystourethrogram (VCUG) is a frequently performed test to diagnose a variety of urologic conditions, such as vesicoureteral reflux (VUR). The test results determine whether continued observation or an interventional procedure is indicated. VCUGs are ordered by many specialists and primary care providers, including pediatricians, family practitioners, nephrologists, hospitalists, emergency room physicians, and urologists. Current protocols for performing and interpreting a VCUG are based on the International Reflux Study in 1985. However, more recent information provided by many national and international institutions suggests a need to refine those recommendations. The lead author of the 1985 study, R.L. Lebowitz, agreed to and participated in the current protocol. In addition, a recent survey directed to the chairpersons of pediatric radiology of 65 children's hospitals throughout the United States and Canada showed that VCUG protocols vary substantially. Recent guidelines from the American Academy of Pediatrics (AAP) recommend a VCUG for children between 2 and 24 months of age with urinary tract infections but did not specify how this test should be performed. To improve patient safety and to standardize the data obtained when a VCUG is performed, the AAP Section on Radiology and the AAP Section on Urology initiated the current VCUG protocol to create a consensus on how to perform this test., (Copyright © 2016 American Academy of Pediatrics. Published by Elsevier Ltd.. All rights reserved.)