Vesicoureteral Reflux Patients Research Articles

High-grade Vesicoureteral Reflux in Patients With Anorectal Malformation From the ARM-Net Registry: Is Our Screening Sufficient?

BackgroundVesico-ureteral reflux (VUR) is a common associated urological anomaly in anorectal malformation (ARM)-patients. High-grade VUR requires antibiotic prophylaxis to prevent urinary tract infections (UTI's), renal scarring and -failure. The exact prevalence of high-grade VUR in ARM patients is unknown. Hence, the aim of this study was determining the incidence of high-grade VUR in ARM-patients, and its associated risk factors. MethodsA multicenter retrospective cohort study was performed using the ARM-Net registry, including data from 34 centers. Patient characteristics, screening for and presence of renal anomalies and VUR, sacral and spinal anomalies, and sacral ratio were registered. Phenotypes of ARM were grouped according to their complexity in complex and less complex. Multivariable analyses were performed to detect independent risk factors for high-grade (grade III-V) VUR. ResultsThis study included 2502 patients (50 % female). Renal screening was performed in 2250 patients (90 %), of whom 648 (29 %) had a renal anomaly documented. VUR-screening was performed in 789 patients (32 %), establishing high-grade VUR in 150 (19 %). In patients with a normal renal screening, high-grade VUR was still present in 10 % of patients. Independent risk factors for presence of high-grade VUR were a complex ARM (OR 2.6, 95 %CI 1.6–4.3), and any renal anomaly (OR 3.3, 95 %CI 2.1–5.3). ConclusionsAlthough renal screening is performed in the vast majority of patients, only 32 % underwent VUR-screening. Complex ARM and any renal anomaly were independent risk factors for high-grade VUR. Remarkably, 10 % had high-grade VUR despite normal renal screening. Therefore, VUR-screening seems indicated in all ARM patients regardless of renal screening results, to prevent sequelae such as UTI's, renal scarring and ultimately renal failure. Type of StudyObservational Cohort-Study. Level of EvidenceIII.

Neutrophil-to-lymphocyte ratio as a predictor of primary vesicoureteral reflux evolution in children with associated acute pyelonephritis.

Neutrophil-to-lymphocyte ratio (NLR) has been recently postulated as an inflammatory biomarker for the diagnosis of vesicoureteral reflux (VUR). The aim of this study is to determine the role of NLR as a predictor of evolution of primary VUR in patients with associated acute pyelonephritis (APN). A retrospective observational cohort study was performed in patients with APN episodes with associated primary VUR diagnosed between 2013-2020. Patients were divided into two groups according to VUR evolution after APN: group A [spontaneous resolution (SR)] and group B [VUR complications development (CD) during follow-up: new APN or renal function worsening]. Demographic, prenatal, laboratory, microbiological and radiological data were analysed. Sensitivity and specificity for CD of VUR was determined by receiver operating characteristic (ROC) curves. A total of 1,146 episodes of APN were analysed of which 273 patients with APN and associated primary VUR were finally included (median age of 11 months at APN diagnosis). SR of VUR occurred in 169 patients (SR group), while CD were observed in the remaining 104 patients (CD group). No differences in demographic, prenatal, microbiological and radiological features were observed. CD patients had significantly higher levels of leukocytes, neutrophils, NLR, C-reactive protein and creatinine. NLR was the parameter with the highest area under the curve (AUC =0.966) for predicting the development of VUR complications (cut-off point =3.41) with a maximum sensitivity of 92.7% and specificity of 91.1% (P<0.001). NLR may be considered as a simple and cost-effective predictor of clinical outcome of VUR, which may correlate with the increased risk of developing complications of primary VUR after an episode of APN. Therefore, it should be included in the management algorithm for these patients, although future prospective studies are still required to confirm these results.

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.&#x0D; 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."&#x0D; 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).&#x0D; 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."

How the 99mTc-DMSA scintigraphy findings are reflected in the adopted treatment of primary vesicoureteral reflux: One centre experience

Renal changes may have long-term sequalae and prevention is a main goal of management of primary vesicoureteral reflux (VUR). This study aims to reveal how much 99mTc-DMSA scintigraphy findings are reflected in the adopted surgical or non-surgical treatment in children with diagnosed primary VUR and to give the clinicians information regarding their final therapeutic decision. A total 207 children with primary VUR who underwent non-acute 99mTc-DMSA scan were retrospectively evaluated. The presence of renal changes, their grading, differential function asymmetry (<45%) and grade of VUR were compared with subsequent choice of therapy. Altogether 92 (44%) children had asymmetric differential function, 122 (59%) showed presence of renal changes, 79 (38%) had high-grade VUR (IV-V). Patients with renal changes had lower differential function (41%vs.48%) and higher grade of VUR. The incidence of high-grade changes (G3+G4B) afflicting more than one third of the kidney was significantly different between grade I-II, III and IV-V VUR (9%, 27%, 48%, respectively). Renal changes were detected in 76% of surgically and 48% of non-surgically treated patients, high-grade 99mTc-DMSA changes in 69% and 31%, respectively. In children with no scars/dysplasia (G0+G4A), non-surgical treatment prevailed in 77%. The independent predictors for surgical intervention were presence of renal changes and higher grade of VUR, but not functional asymmetry. Over the last 20 years, there has been a shift toward more non-surgical management of VUR. The long-term outcome of this approach should be thoroughly studied. This is the first study analysing renal status in VUR patients using 99mTc-DMSA scan and its grading regarding the adopted treatment. Renal changes in almost half of non-surgically treated children with VUR should be an indicator for earlier diagnosis and effective treatment of acute pyelonephritis and VUR. We recommend distinguishing grade III VUR, as a moderate-grade VUR, because it is linked to higher incidence of high-grade 99mTc-DMSA changes (G3+G4B); our findings of 65% of grade III VURs treated non-surgically should be cautionary. Grade III VUR does not mean a low-risk condition and should alert the clinician to evaluate the extent of renal changes and unmask high-risk cases. Our data strengthens the need to investigate the extent of renal changes in VUR patients regarding treatment decision. Performing 99mTc-DMSA scan individualizes the treatment of VUR patients; its grading can distinguish grade III-VUR as a separate risk entity because it differs significantly in terms of incidence of high-grade renal changes and chosen therapy.

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.

A predictive score for detecting vesicoureteral reflux in children with their first Escherichia coli-induced urinary tract infection.

In children with a first Escherichia coli-induced febrile urinary tract infection (fUTI), routine voiding cytourethrography (VCUG) is not recommended for detecting vesicoureteral reflux (VUR). Meanwhile, the sensitivity of renal and bladder ultrasound (RBUS) for detecting VUR is insufficient. Aiming to implement VCUG properly for children with a first E.coli-induced fUTI, we attempted to construct a predictive scoring system for the early screening of VUR. This study enrolled patients aged <2 years of age hospitalized for their first E.coli-induced fUTI during the period when VCUG was implemented for all patients (2007-14, non-selective group [n = 111]) and only for those with VUR-suspected RBUS findings, bacteremia or acute focal bacterial nephritis (2016-19, selective group [n = 102]). We evaluated the accuracy of the current criteria and the VUR predictive score constructed using data from the non-selective group. In the non-selective group, 32 patients had VUR (29%). In the selective group, 20 of 45 VCUG-tested patients had VUR (44%). Among 57 patients not undergoing VCUG in the selective group, 8 had a recurrence of fUTI, 3 of whom were diagnosed with VUR. In the non-selective group, 9 patients with VUR did not fulfill the current criteria and the VUR predictive score consisting of young age, female sex, prolonged fever, hypoproteinemia, hyponatremia and hyperglycemia, showed higher sensitivity, specificity than the current criteria. The current imaging/bacteriological criteria were ineffective in screening for VUR in patients with their first E.coli-induced fUTI. The VUR predictive score can be an accurate indicator for implementing VCUG.

Epidemiologic, microbiologic and imaging characteristics of urinary tract infections in hospitalized children < 2 years of age diagnosed with anatomic abnormalities of the urinary tract.

To compare the epidemiologic, microbiologic and imaging characteristics of urinary tract infections (UTI) in children <2 years of age with and without anatomic urinary tract abnormalities (AA). All children hospitalized with UTI during 1.1.2005-31.12.2018 were included. The study group (patients with AA) included 76 patients. The control group (99 patients) included patients without AA. 1163 children were hospitalized. Age at diagnosis was younger in the study group vs. controls (5.2±6.0 vs. 7.9±7.5 months, P=0.038). Uropathogens distribution was different (P=0.007), with lower Escherichia coli (Ec) and Proteus mirabilis (Pm) percentages in the study group and higher percentages of Enterococcus spp. (Ent) in controls. In the study group, Ec nonsusceptibility rates to ampicillin, amoxicillin/clavulanic acid, cefazolin, cefuroxime, TMP/SMX and ceftriaxone were 58%, 40%, 14%, 14%, 12% and 10%, respectively, with no differences vs. controls. Ultrasound (US) was performed in 69/76 (98%) patients with AA (84.1%, abnormal); bilateral (39.7%) and unilateral (32.7%) ureteral dilatation were the most frequent findings. Voiding cystourethrography was performed in 46 patients (pathologic in 35, 76%); 31 (81.6%) patients had vesicoureteral reflux (VUR) (bilateral in 11, 35.5%; grade 4/5 in 7 patients). Uropathogens distribution in VUR patients differed between study and control groups, with lower Ec and Pm in the first group and higher Pseudomonas aeruginosa and Ent percentages in the control group. Age at diagnosis was lower and pathogen distribution was different in patients with AA. Antibiotic susceptibility patterns of the main uropathogens were similar between patients with or without AA.

Ureteral reimplantation during augmentation cystoplasty is not needed for vesicoureteral reflux in patients with neurogenic bladder: a long-term retrospective study

BackgroundTo investigate the need for ureteral reimplantation for vesicoureteral reflux (VUR) during augmentation cystoplasty (AC) in the long term.MethodsA total of 19 patients with a median age at surgery of 14 years (3–38 years) who underwent AC for neurogenic bladder with VUR between 1983 and 2016 were included in this study. The changes in VUR grade and urodynamic findings were retrospectively evaluated. We evaluated the renal function by periodic inspection of serum creatinine level and estimated glomerular filtration rate; eGFR.ResultsThe median follow-up period from AC was 14.8 years (5.7–30 years). VUR was detected in 19 patients, involving 27 ureters. Reflux grade was V in 6, IV in 9, III in 5, II in 6, and I in 1. Ureteral reimplantation was not performed in 18 patients (26 ureters), whereas it was done for 1 patient (1 ureter) in the early era of our experience. Postoperative videourodynamics showed that the reflux was radiologically not verifiable in 23 ureters (85%), was downgraded in 3 ureters (11%), and was unchanged in 1 ureter (3%). There were no cases of deterioration of VUR.ConclusionsUreteral reimplantation is not necessary for VUR during augmentation cystoplasty.

Ureteral reimplantation for pediatric vesicoureteral reflux and primary obstructive megaureter: Transvesicoscopic cohen vs. Politano-Leadbetter approaches

Transvesicoscopic approaches for ureteral reimplantation (UR) are effective surgical techniques with which to resolve vesicoureteral reflux (VUR) or primary obstructive megaureter (POM) in pediatric patients. However, the effectiveness of different UR surgical methods for these two diseases is still unclear. To compare the effects of Cohen's cross-trigonal and Politano-Leadbetter techniques in children in need of UR. A retrospective chart review was performed for consecutive patients who underwent UR at our institution between May 2018 and November 2019, including those treated for vesicoureteral reflux (VUR) or primary obstructive megaureter (POM). Patients who underwent Cohen's technique included in Group C, and those who underwent the Politano-Leadbetter technique were included in Group P. Patient characteristics, perioperative parameters, and short-term postoperative outcomes were compared. Forty-six patients who underwent unilateral UR were included in the analysis. At presentation, those in Group P (N=22, 12 diagnosed with VUR and 10 with POM) did not differ from those in Group C (N=24, 12 diagnosed with VUR and 12 with POM) with respect to age, sex, disease type or severity. For VUR patients, reflux was clinically resolved for all patients in both groups; however, only a 75% resolution rate was observed in Group C, with 3 patients experiencing persistent low-grade, clinically insignificant reflux, while a 100% resolution rate was found in Group P (P>0.05). Among POM patients, the obstruction was resolved for all those in Group P and for 90% of those in Group C; this difference was also not statistically significant (P>0.05). At the 1-year follow-up, the ureteral diameter (P<0.05) and anterior-posterior renal pelvic diameter (APRPD) (P<0.05) of Group P were significantly reduced, and differential renal function (DRF) (P<0.05) was slightly improved compared with that in Group C in both VUR and POM patients. Politano-Leadbetter and Cohen are both reliable techniques for UR in children with VUR or POM, and the short-term outcomes of these methods in solving reflux and obstruction are comparable. Besides traditional Cohen's technique, Politano-Leadbetter's technique maybe a potential choice for ureteral reimplantation in children.

Efficacy of Bladder Ultrasound in Prediction of Resolution of Vesicoureteral Reflux After Endoscopic Subureteral Hyaluronic Acid/Dextranomer (Deflux) Injection

ObjectiveTo evaluate the efficacy of bladder ultrasound (US) in predicting the resolution of vesicoureteral reflux (VUR) after subureteral endoscopic Deflux injection in low-grade vs high-grade VUR patients. Materials and MethodsBetween 2014 and 2020, 160 children (220 ureters) were administered subureteral Deflux injection for treatment of primary VUR. The mean age at surgery was 72 months. Low-grade reflux (grades II-III) was observed in 190 ureters and high-grade reflux (grades IV-V) was observed in 30 ureters. Bilateral surgery was performed in 60 patients. All patients had follow-up using bladder US and voiding cystourethrography (VCUG) at 3 months and 12 months. Outcome included identification of Deflux mounds by bladder US and correlation of Deflux mounds identified with radiographic success rates of VUR on VCUG. ResultsSingle Deflux injection showed radiographic success rates in 98% of low grade reflux patients and 26.7% of high grade reflux patients at last follow-up. Bladder US was able to detect Deflux mounds in 89% of low grade reflux and 43.3% of high grade reflux patients at last follow up. Our study demonstrated higher sensitivity, Positive predictive value and accuracy in Deflux detection by bladder US in low grade reflux vs high grade reflux patients. ConclusionBladder-US was highly sensitive for detection of Deflux implants. Bladder-US could be adjusted in follow-up of patients with low-grade reflux treated by Deflux injection, while VCUG could be preserved for follow-up of high-grade reflux, this will lead to reduction of unnecessary radiation exposure during VCUG for children with low grade reflux.

Risk factors for renal scarring and clinical morbidity in children with high-grade and low-grade primary vesicoureteral reflux

Primary vesicoureteral reflux (VUR) is associated with urinary tract infections (UTIs) and renal damage. However, the importance of early diagnosis of VUR has been questioned. Moreover, most studies have few patients with high-grade VUR. Hence, we retrospectively analyzed a large cohort of patients with primary high-grade and low-grade VUR and assessed risk factors for renal damage and clinical morbidity. We included patients (<18 years) at diagnosis with low-grade (1-3) or high-grade (4-5) primary VUR and noted their clinical history and presence of hypertension, low eGFR (<60ml/in/1.73m2), renal scarring (focal or generalised) and reduced differential renal function (DRF; <45%). Risk factors were assessed (in patients and renal units) by logistic regression and generalised estimating equation. Of 399 primary VUR patients, 255 (64%) had high-grade VUR. Indications for voiding cystourethrogram were recurrent UTI (38%), first UTI (28%) and antenatal hydronephrosis (17%). At diagnosis, 252 (65%) had renal scars (focal in 170 [44%], generalised in 82 [21%]), and 188 (47%) had reduced DRF. High-grade VUR patients were more likely than low-grade VUR patients to have renal scarring (75% vs. 49%, p<0.01), low eGFR (23% vs. 13%, p=0.04) and significant hypertension (26% vs. 13%, p=0.02). High-grade VUR was associated with generalised scars (odds ratio [OR] 11, p<0.001), focal scars (OR 3.1, p<0.001) and reduced DRF (OR 2.3, p<0.001) shown in the table. Male sex was a risk factor for generalised scars (OR 2.3, p=0.005). Focal scars were associated with recurrent UTIs (OR=1.8, p=0.004) and reduced DRF (OR 1.4, p=0.027). Patients with multiple focal scars were diagnosed at an older age (2 years [1,4] than those with single scars (1.5 years [1,4] or no scars (1 year [0, 3]), p=0.04). The prevalence of renal damage and clinical morbidity at VUR diagnosis was higher than other studies. High-grade VUR patients had a greater prevalence of renal damage, low eGFR and hypertension than low-grade VUR patients and was a risk factor for focal scars, generalised scars and reduced DRF. Focal scars were independently associated with recurrent UTI. Those with multiple scars were diagnosed later than those with single scars or no scars. High-grade VUR was associated with renal damage and clinical morbidity. Our study highlights the importance of diagnosing VUR early to identify patients who may warrant long-term follow-up and intervention to minimize morbidity.

Utility of Urinary Biomarkers Neutrophil Gelatinase-Associated Lipocalin and Kidney Injury Molecule-1 as a Marker for Diagnosing the Presence of Renal Scar in Children with Vesicoureteral Reflux (VUR): A Cross-Sectional Study.

Aim:To explore the possibility of using urinary biomarkers neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) to assess the presence of renal scars in children with Vesicoureteric Reflux (VUR).Materials and Methods:This cross-sectional study was conducted in 94 children aged 0–16 years diagnosed with VUR in the Department of Pediatric Surgery, JIPMER. Urinary biomarkers were measured using the enzyme-linked immunosorbent assay kits, normalized with urinary creatinine (Cr) and compared with severity of VUR (low grade [I and II] and high grade [III, IV, and V]), presence or absence of renal scar in VUR patients and severity of renal scar. Independent Student's t-test, Mann–Whitney U-test, and analysis of variance Kruskal–Wallis test were used for comparison, and receiver operating characteristic (ROC) curve analysis for predicting the accuracy of biomarkers in detecting the presence of renal scars.Results:The median urinary NGAL (uNGAL) value was higher in children with renal scar (1.49 ng/mL) than those without renal scar (0.58 ng/mL) and was statistically significant (<0.001). Whereas median uNGAL/Cr was higher in children with renal scar (0.07) than those without renal scar (0.03) but was not statistically significant (P = 0.06). Urinary KIM-1 and urinary KIM-1/urinary Cr (uKIM-1/Cr) was not found to be a significant predictor of renal scar. The difference of uNGAL/Cr was comparable between the grades of renal scar but was not statistically significant. On ROC curve analysis, uNGAL had area under the ROC curve (AUC) of 0.769 with 71% of both specificity and sensitivity, whereas uNGAL/Cr was found to be a poor predictor of renal scar with AUC of 0.611, 60% sensitivity, and 61.2% specificity.Conclusion:uNGAL can serve as a noninvasive marker for diagnosing the presence of renal scar in children with VUR and a multicentric more extensive cohort study may be needed to strengthen or negate its role.

Evaluation of the Relationship of the Time of Vesicoureteral Reflux Between Renal Scar Development and Endoscopic Treatment Success in Early Childhood

INTRODUCTION: Vesicoureteral reflux (VUR) is an important cause of urinary tract infection and chronic renal disease. Voiding cystourethrography (VCUG) is the gold standard diagnostic test in the diagnosis of VUR. In recent years, new parameters related to VCUG have been more objectively studied to evaluate the clinical prognosis. It is aimed to evaluate the effect of reflux time in primary VUR in terms of predicting endoscopic treatment success and treatment timing in VUR management. METHOD: In our study, the records and imaging findings of children with primary VUR who underwent VCUG examination between 2012 and 2019, who were treated with endoscopic injections, were retrospectively reviewed. Forty one children (67 renal units) were included in our study. Patients with preoperative VCUG, urinary ultrasonography, dimercaptosuccinic acid (DMSA) renal scan, and post-operative control VCUG were included in this study. RESULTS: Patients with preoperative VUR grade 1-2 were divided into two groups as “low grade” and patients with stage 3-4-5 as “high grade”. In the general patient population, endoscopic success rates in terms of renal unit deficit were found to be 46.3% (31/67). When the subgroup was analyzed, the endoscopic treatment success rate was 72.2% (13/18) in the low-grade group, versus 36.7% (18/49) in the high-grade group (p = 0.010). In the multivariate logistic regression analysis performed to identify independent predictors of scarring, reflux degree and reflux time were found to be independent predictors of scarring. CONCLUSION: In our study, we found that in VCUG evaluated preoperatively, VUR time as well as VUR grade were effective on endoscopic success rate and scar development. Based on these results, it could be thought that VUR time may be effective in selecting the best candidates for surgery and in the management and timing of treatment of VUR patients.

Urinary exosomal vitronectin predicts vesicoureteral reflux in patients with neurogenic bladders and spinal cord injuries.

Neurogenic bladder (NGB) is an important complication of urinary tract dysfunction after spinal cord injury (SCI). However, using urodynamics and urography to guide therapy remains invasive and complicated. Therefore, the present study aimed to identify potential noninvasive biomarkers from urinary exosomes that can facilitate diagnosis and guide prognosis of patients with NGB subsequent to SCI. Urinary exosomes were isolated, and their proteome profile was analyzed by mass spectrometry. Transmission electron microscopy and Nanoparticle Tracking Analysis confirmed the size and morphological characteristics of urinary exosomes. In addition, bioinformatics analysis and parallel reaction monitoring (PRM) were used to screen candidate biomarkers. The selected biomarkers were validated using western blotting and ELISA. Mass spectrometry identified 134 upregulated proteins and 99 downregulated proteins between the vesicoureteral reflux (VUR) and non-VUR groups. A total of 18 candidate proteins were selected for PRM validation, but only vitronectin (VTN) and α-1 type I collagen (COL1A1) demonstrated significant differences. In the validation experiments using western blotting and ELISA, VTN was exclusively highly expressed in VUR patients compared with non-VUR patients. However, the ELISA results of COL1A1 revealed no significant difference when a larger sample size was used. Furthermore, a receiver operating characteristic curve of ELISA-based VTN demonstrated an area under the curve of 0.795 and 80% sensitivity at a threshold set to give 82.9% specificity. Collectively, these results suggested that VTN in urinary exosomes may be used as a biomarker to predict the progression and guide the prognosis of NGB.

Urinary Tract Infections in Children with Vesicoureteral Reflux Are Accompanied by Alterations in Urinary Microbiota and Metabolome Profiles

Children with vesicoureteral reflux (VUR) are at an increased risk of recurrent urinary tract infections (UTIs) and renal scarring. Gut microbiota are associated with disease phenotypes, but there has been no study that associates urinary microbiota (uMB) and metabolic profiles with VUR pathology. To identify dominant uMB genera and metabolites associated with UTIs in VUR, urine samples collected under sterile conditions underwent 16S ribosomal RNA sequencing (n = 49) and metabolomic analysis by mass spectrometry (n = 96). Alterations in uMB and metabolomic profiles in VUR patients suggest remodeling of urinary bacterial communities after UTIs: Dorea- and Escherichia-dominant uMB profiles were more frequently identified in participants with VUR. Prevotella- and Lactobacillus-dominant uMB profiles were more prevalent in controls (p < 0.001). Microbial composition varied based on recurrent febrile UTI status (p = 0.001). A total of 243 urinary metabolites involved in energy, amino acid, nucleotide, and lipid metabolism were altered in VUR patients with UTIs (p < 0.05). Importantly, VUR specimens revealed changes in the bacteria-associated metabolic pathways such as glutamate degradation, methyl-citrate cycle, and bile acid metabolism. Patient summaryDifferences in urinary commensal bacteria and metabolites exist between children with and without vesicoureteral reflux (VUR). These changes may be utilized to identify patients at risk of VUR-associated kidney damage.

Pyelonephritis in Pediatric Uropathic Patients: Differences from Community-Acquired Ones and Therapeutic Protocol Considerations. A 10-Year Single-Center Retrospective Study.

Pyelonephritis (PN) represents an important cause of morbidity in the pediatric population, especially in uropathic patients. The aim of the study is to demonstrate differences between PNs of uropathic patients and PNs acquired in community in terms of uropathogens involved and antibiotic sensitivity; moreover, to identify a proper empiric therapeutic strategy. A retrospective study was conducted on antibiograms on urine cultures from PNs in vesicoureteral reflux (VUR) patients admitted to pediatric surgery department and from PNs in not VUR patients admitted to Pediatric Emergency Unit between 2010 and 2020. We recorded 58 PNs in 33 patients affected by VUR and 112 PNs in the not VUR group. The mean age of not VUR patients at the PN episode was 1.3 ± 2.6 years (range: 20 days of life–3 years), and almost all the urine cultures, 111 (99.1%), isolated Gram-negative bacteria and rarely, 1 (0.9%), Gram-positive bacteria. The Gram-negative uropathogens isolated were Escherichia coli (97%), Proteus mirabilis (2%), and Klebsiella spp. (1%). The only Gram-positive bacteria isolated was an Enterococcus faecalis. As regards the antibiograms, 96% of not VUR PNs responded to beta-lactams, 99% to aminoglycosides, and 80% to sulfonamides. For the VUR group, mean age was 3.0 years ± 3.0 years (range: 9 days of life–11 years) and mean number of episodes per patient was 2.0 ± 1.0 (range: 1–5); 83% of PNs were by Gram-negatives bacteria vs. 17% by Gram-positive: the most important Gram-negative bacteria were Pseudomonas aeruginosa (44%), Escherichia coli (27%), and Klebsiella spp. (12%), while Enterococcus spp. determined 90% of Gram-positive UTIs. Regimen ampicillin/ceftazidime (success rate: 72.0%) was compared to ampicillin/amikacin (success rate of 83.0%): no statistically significant difference was found (p = 0.09). The pathogens of PNs in uropathic patients are different from those of community-acquired PNs, and clinicians should be aware of their peculiar antibiotic susceptibility. An empiric therapy based on the association ampicillin + ceftazidime is therefore suggested.

Copy Number Variant Analysis and Genome-wide Association Study Identify Loci with Large Effect for Vesicoureteral Reflux.

Vesicoureteral reflux (VUR) is a common, familial genitourinary disorder, and a major cause of pediatric urinary tract infection (UTI) and kidney failure. The genetic basis of VUR is not well understood. A diagnostic analysis sought rare, pathogenic copy number variant (CNV) disorders among 1737 patients with VUR. A GWAS was performed in 1395 patients and 5366 controls, of European ancestry. Altogether, 3% of VUR patients harbored an undiagnosed rare CNV disorder, such as the 1q21.1, 16p11.2, 22q11.21, and triple X syndromes ((OR, 3.12; 95% CI, 2.10 to 4.54; P=6.35×10-8) The GWAS identified three study-wide significant and five suggestive loci with large effects (ORs, 1.41-6.9), containing canonical developmental genes expressed in the developing urinary tract (WDPCP, OTX1, BMP5, VANGL1, and WNT5A). In particular, 3.3% of VUR patients were homozygous for an intronic variant in WDPCP (rs13013890; OR, 3.65; 95% CI, 2.39 to 5.56; P=1.86×10-9). This locus was associated with multiple genitourinary phenotypes in the UK Biobank and eMERGE studies. Analysis of Wnt5a mutant mice confirmed the role of Wnt5a signaling in bladder and ureteric morphogenesis. These data demonstrate the genetic heterogeneity of VUR. Altogether, 6% of patients with VUR harbored a rare CNV or a common variant genotype conferring an OR >3. Identification of these genetic risk factors has multiple implications for clinical care and for analysis of outcomes in VUR.

The Outcome of Transurethral Electro-Endoscopic Resection of Orthotopic Single System Ureterocoeles in Adults Nigerians.

Endoscopic transurethral electro-incision and resection are minimally invasive options for treating adult single system ureterocoele. Vesicoureteral (VU) reflux is frequently associated with ureterocoeles and can complicate the treatment. The literature on endoscopic management isscanty from sub-Saharan Africa. This study aimed to describe the technique and outcome of adult patients who had transurethral incision and or deroofing of orthotopic single system ureterocoele. This was a prospective study on patients who presented with single system ureterocoeles. All were diagnosed either by computerized axial tomography urography or intravenous urography and were followed up and monitored for resolution of symptoms, development of urinary tract infection, and ureterovesical reflux. The patients' demographic information such as their age, sex, details of endoscopic treatments, complications on follow-up were entered into Excel and analyzed using SPSS version 21. There were eighteen ureteric units managed in 10 patients with single system ureterocoeles. The male: female ratio was 3:2. The 30-39-year age group (four; 40%) and 60-69year age groups (four; 40%) had the highest frequency. Six (33.33%) had calculi, and 83.30% presented with lower urinary tract symptoms (LUTS). Nine (50%) of the ureteric systems had transurethral deroofing of ureterocoele (TUDU), while eight (44.4%) had transurethral incision of ureterocoele (TUIU). Urinary tract infection was the commonest complication. Ureterovesical reflux was present in two and two developed refluxes after TUDU. The patients with refluxes had antibiotics with the resolution of the ipsilateral symptoms. All had preserved renal function. VU reflux inpatients that underwent endoscopic incision or deroofing for single system ureterocoele is infrequent and can be managed conservatively. It is an effective treatment for single system ureterocoeles and has minimal complications.

The Change in the Renal Pelvis Anterior-Posterior Diameter Between Prevoiding and Postvoiding Status, and Its Correlation With Vesicoureteral Reflux.

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.

An Important Risk Factor Affecting Hypercalciuria in Children: Vesicoureteral Reflux.

A large number of genes and environmental factors, like dietary habits, play a role in the development of hypercalciuria in children. In this study, we aimed to determine the effects of the presence and grade of vesicoureteral reflux (VUR) on hypercalciuria status in children. Data for 165 patients who admitted to the Pediatric Urology Department were retrospectively analyzed. The patients were composed of following four different groups: (1) urinary stone patients, (2) VUR patients under follow-up, (3) corrected VUR patients, and (4) control. The demographic features, clinical data, and laboratory tests for the groups were compared. The mean age of the patients was 100.6 ± 54.69 months and the female/male ratio was 79:86. The mean urinary calcium/creatinine (UCa/Cr) excretion and the frequency of high UCa/Cr ratios in the corrected VUR group were similar to those in the control group (p = 0.375 and 0.965, respectively). In contrast, the mean UCa/Cr excretion and frequency of high UCa/Cr ratios in the urinary stone and follow-up VUR groups were significantly higher than those in the corrected VUR group (p < 0.001, < 0.001, 0.003, and 0.029, respectively). The mean UCa/Cr excretion and frequency of high UCa/Cr ratios in the follow-up VUR group were similar to those in the urinary stone group (p = 0.323 and 0.425, respectively). In the follow-up VUR group, although reflux laterality had no effect on the UCa/Cr ratios (p = 0.180 and 0.108, respectively), the mean and frequency of high UCa/Cr ratios were higher in high-grade reflux cases (p < 0.001 and p = 0.042, respectively). Both the mean UCa/Cr ratio and the rate of hypercalciuria in the corrected reflux group were significantly lower than the corresponding values in the follow-up VUR and urinary stone groups. Further, the follow-up VUR patients had similar urinary calcium excretion levels as the stone patients. VUR treatment is associated with a decrease in urinary calcium excretion to the normal population level. A positive correlation between reflux degree and calcium excretion was observed.