BACKGROUND: Childhood urinary tract infection (UTI) can cause renal scarring, and possibly hypertension, chronic kidney disease (CKD), and end-stage renal failure (ESRF). Previous studies have focused on selected populations, with severe illness or underlying risk factors. The risk for most children with UTI is unclear.
OBJECTIVE: To examine the association between childhood UTI and outcomes in an unselected population of children.
METHODS: A retrospective population-based cohort study using linked GP, hospital, and microbiology records in Wales, UK.
METHODS: Participants were all children born in 2005-2009, with follow-up until 31 December 2017. The exposure was microbiologically confirmed UTI before the age of 5 years. The key outcome measures were renal scarring, hypertension, CKD, and ESRF.
RESULTS: In total, 159 201 children were included; 77 524 (48.7%) were female and 7% (n = 11 099) had UTI before the age of 5 years. A total of 0.16% (n = 245) were diagnosed with renal scarring by the age of 7 years. Odds of renal scarring were higher in children by age 7 years with UTI (1.24%; adjusted odds ratio 4.60 [95% confidence interval [CI] = 3.33 to 6.35]). Mean follow-up was 9.53 years. Adjusted hazard ratios were: 1.44 (95% CI = 0.84 to 2.46) for hypertension; 1.67 (95% CI = 0.85 to 3.31) for CKD; and 1.16 (95% CI = 0.56 to 2.37) for ESRF.
CONCLUSIONS: The prevalence of renal scarring in an unselected population of children with UTI is low. Without underlying risk factors, UTI is not associated with CKD, hypertension, or ESRF by the age of 10 years. Further research with systematic scanning of children\'s kidneys, including those with less severe UTI and without UTI, is needed to increase the certainty of these results, as most children are not scanned. Longer follow-up is needed to establish if UTI, without additional risk factors, is associated with hypertension, CKD, or ESRF later in life.

BACKGROUND: Febrile urinary tract infections (UTIs) are among the most severe bacterial infections in infants, in which a subset of patients develops complications. Identifying infants at risk of recurrent infections or kidney damage based on clinical signs is challenging. Previous observations suggest that genetic factors influence UTI outcomes and could serve as predictors of disease severity. In this study, we conducted a nationwide survey of infant genotypes to develop a strategy for infection management based on individual genetic risk. Our aims were to identify genetic susceptibility variants for renal scarring (RS) and genetic host factors predisposing to dilating vesicoureteral reflux (VUR) and recurrent UTIs.
METHODS: To assess genetic susceptibility, we collected and analyzed DNA from blood using exome genotyping. Disease-associated genetic variants were identified through bioinformatics analysis, including allelic frequency tests and odds ratio calculations. Kidney involvement was defined using dimercaptosuccinic acid (DMSA) scintigraphy.
RESULTS: In this investigation, a cohort comprising 1087 infants presenting with their first episode of febrile UTI was included. Among this cohort, a subset of 137 infants who underwent DMSA scanning was subjected to gene association analysis. Remarkable genetic distinctions were observed between patients with RS and those exhibiting resolved kidney involvement. Notably, the genetic signature indicative of renal scarring prominently featured mitochondrial genes.
CONCLUSIONS: In this nationwide study of genetic susceptibility to RS after febrile UTIs in infancy, we identified a profile dominated by mitochondrial polymorphisms. This profile can serve as a predictor of future complications, including RS and recurrent UTIs.

OBJECTIVE: The prescriptive literature on vesicoureteral reflux (VUR) is still limited and thus the level of evidence is generally low. The aim of these guidelines is to provide a practical approach to the treatment of VUR that is based on risk analysis and selective indications for both diagnostic tests and interventions. We provide a 2023 update on the chapter on VUR in children from the European Association of Urology (EAU) and European Society for Paediatric Urology (ESPU) guidelines.
METHODS: A structured literature review was performed for all relevant publications published from the last update up to March 2022.
UNASSIGNED: The most important updates are as follows. Bladder and bowel dysfunction (BBD) is common in toilet-trained children presenting with urinary tract infection (UTI) with or without primary VUR and increases the risk of febrile UTI and focal uptake defects on a radionuclide scan. Continuous antibiotic prophylaxis (CAP) may not be required in every VUR patient. Although the literature does not provide any reliable information on CAP duration in VUR patients, a practical approach would be to consider CAP until there is no further BBD. Recommendations for children with febrile UTI and high-grade VUR include initial medical treatment, with surgical care reserved for CAP noncompliance, breakthrough febrile UTIs despite CAP, and symptomatic VUR that persists during long-term follow-up. Comparison of laparoscopic extravesical versus transvesicoscopic ureteral reimplantation demonstrated that both are good option in terms of resolution and complication rates. Extravesical surgery is the most common approach used for robotic reimplantation, with a wide range of variations and success rates.
CONCLUSIONS: This summary of the updated 2023 EAU/ESPU guidelines provides practical considerations for the management and diagnostic evaluation of VUR in children.
UNASSIGNED: For children with VUR, it is important to treat BBD if present. A practical approach regarding the duration of CAP is to consider administration until BBD resolution.
RESULTS: We provide a summary and update of guidelines on the diagnosis and management of urinary reflux (where urine flows back up through the urinary tract) in children. Treatment of bladder and bowel dysfunction is critical, as this is common in toilet-trained children presenting with urinary tract infection.

Our study aimed to investigate the association between the characteristics of patients/images and complete remission of renal scarring shown in the first chronic phase Technetium-99m dimercaptosuccinic acid (DMSA) renal scintigraphy images in children with urinary tract infection (UTI). Fifty children, who underwent the chronic phase of DMSA scintigraphy more than twice following UTI diagnosis and had renal scarring in the first chronic phase DMSA renal scintigraphy, were enrolled. They were classified into 2 groups: with and without complete remission of renal scarring on the second chronic phase DMSA renal scintigraphy. Renal scarring was classified into 3 grades based on severity per the image findings. Seven cases had complete remission from renal scarring. There were significant differences in age and severity. Renal scarring might be completely reversed in young children without severe findings on DMSA renal scintigraphy. Additional chronic phase examination may aid in follow-up completion and patients\' peace of mind.

To review the urological outcomes of proactive versus delayed management of children with a neurogenic bladder (NB).
We performed a literature search on EMBASE, MEDLINE, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials between January 1, 2000 to August 21, 2023 for studies investigating the management of spina bifida-associated NB in pediatric patients (0-18 years of age). Proactive management was defined as use of clean intermittent catheterization, and/or anticholinergics at presentation, or based on initial high-risk urodynamic findings by 1 year of age. Delayed management was defined as beginning management after 1 year of age or no intervention. Outcomes included incidence or diagnosis of secondary vesicoureteral reflux (VUR), urinary tract infection (UTI), and renal deterioration, which included renal scarring, loss of differential renal function on a nuclear scan, or a decrease in renal function defined by glomerular filtration rate or serum creatinine estimation. Forest plots were synthesized using the Inverse Variance method with random-effect model. The Risk of Bias was assessed using the ROBINS-I tool.
We included 8 observational studies on 652 pediatric patients with spina bifida-associated NB (mean follow-up - 7 years). Proactive management following initial assessment was associated with significantly lower risks of secondary VUR (OR 0.37 [0.19, 0.74], p = 0.004), non-febrile UTI (OR 0.35 [0.19, 0.62], p = 0.0004), and renal deterioration (OR 0.31 [0.20, 0.47], p < 0.00001).
Delayed management of NB potentially has 3 times higher risks of secondary VUR, non-febrile UTI, and renal deterioration. However, the evidence is limited by the high risk of bias due to lack of randomization and standardized reporting in observational studies.
While further well-defined prospective studies with long-term follow-up should be conducted to confirm this finding, this study supports the EAU/ESPU recommendations for early intervention in children with NB.

We aimed to detect complications and associated risk factors in patients with renal scarring (RS) secondary to recurrent urinary tract infections (UTI).
Fifty patients with RS were compared with 25 patients without RS by means of, serum creatinine, 24- hour urinary creatinine clearance, and 24-hour urinary albumin levels. Office blood pressure (BP) examination and ambulatory BP monitoring (ABPM) were also performed.
Vesicoureteral reflux was detected in 50 patients. Glomerular filtration rate (GFR) < 90 ml/min/1.73 m2 was observed in 5 patients with RS but in no patient without RS. Albuminuria was significantly higher in patients with bilateral RS and severe RS. Patients with albuminuria had a significantly lower GFR than those without. All patients with ambulatory hypertension (HT) were in the RS group, and 60% of those had isolated nocturnal HT. Compared to those without RS, patients with RS had significantly higher SDS values for all BP readings, 24-hour and nighttime systolic and diastolic BP loads with significantly lower systolic dipping. GFR was negatively correlated with diastolic BP SDS and diastolic BP load in patients with RS. Daytime diastolic BP load was significantly higher in those with severe RS than in those with mild RS.
Isolated nocturnal HT could be an early sign of complications in RS of UTI. Albuminuria is related to increased BP and impaired renal function. Therefore, ABPM and assessing albuminuria should be a routine part of the follow-up. Diastolic BP elevations could be associated with worse outcomes in these patients.

UNASSIGNED: Urinary tract infection (UTI) in children is a major source of office visits and healthcare expenditure. Research into the diagnosis, treatment, and prophylaxis of UTI has evolved over the past 10 years. The development of new imaging techniques and UTI screening tools has improved our diagnostic accuracy tremendously. Identifying who to treat is imperative as the increase in multi-drug-resistant organisms has emphasized the need for antibiotic stewardship. This review covers the contemporary management of children with UTI and the data-driven paradigm shifts that have been implemented into clinical practice.
UNASSIGNED: With recent data illustrating the self-limiting nature and low prevalence of clinically significant vesicoureteral reflux (VUR), investigational imaging in children has become increasingly less frequent. Contrast-enhanced voiding urosonogram (CEVUS) has emerged as a useful diagnostic tool, as it can provide accurate detection of VUR without the need of radiation. The urinary and intestinal microbiomes are being investigated as potential therapeutic drug targets, as children with recurrent UTIs have significant alterations in bacterial proliferation. Use of adjunctive corticosteroids in children with pyelonephritis may decrease the risk of renal scarring and progressive renal insufficiency. The development of a vaccine against an antigen present on Escherichia coli may change the way we treat children with recurrent UTIs.
UNASSIGNED: The American Academy of Pediatrics defines a UTI as the presence of at least 50,000 CFU/mL of a single uropathogen obtained by bladder catheterization with a dipstick urinalysis positive for leukocyte esterase (LE) or WBC present on urine microscopy. UTIs are more common in females, with uncircumcised males having the highest risk in the first year of life. E. coli is the most frequently cultured organism in UTI diagnoses and multi-drug-resistant strains are becoming more common. Diagnosis should be confirmed with an uncontaminated urine specimen, obtained from mid-stream collection, bladder catheterization, or suprapubic aspiration. Patients meeting criteria for imaging should undergo a renal and bladder ultrasound, with further investigational imaging based on results of ultrasound or clinical history. Continuous antibiotic prophylaxis is controversial; however, evidence shows patients with high-grade VUR and bladder and bowel dysfunction retain the most benefit. Open surgical repair of reflux is the gold standard for patients who fail medical management with endoscopic approaches available for select populations.

Long-term adult outcomes of children diagnosed with urinary tract dilatation (UTD) and vesicoureteral reflux (VUR) are not clearly documented in the literature. Likewise, follow-up protocols for these patients as they transition through adolescence and into adulthood vary with institution and cultures. Several studies have shown that individuals diagnosed with VUR in childhood are at higher risk of urinary tract infection (UTI) throughout their lives, even in the setting of prior VUR resolution or surgical correction. This is particularly relevant in patients with renal scarring, who are at higher risk of UTIs, hypertension and renal function deterioration in pregnancy. The risk of adverse maternal and fetal outcomes in pregnancy are higher for women with significant chronic kidney disease (CKD). Patients who underwent endoscopic injection or reimplantation should be counselled on the long-term particular risks associated with each intervention, including calcification of ureteric injection mounds, and the potential challenges of future endoscopic procedures following reimplantation. Although there is no evidence for the direct correlation between conservatively managed UTD in childhood, and symptomatic UTD diagnosed in adulthood, all patients should be aware of the long-term risks of persistent upper tract dilatation. Lastly, bladder-bowel dysfunction (BBD) management in adolescence can be more challenging and may contribute to symptomatic recurrence in this age group.

Vesicoureteral reflux (VUR) is the commonest congenital anomaly of urinary tract in children. It is mostly diagnosed after a urinary tract infection or during evaluation for congenital anomalies of the kidney and urinary tract. High-grade VUR, recurrent pyelonephritis, and delayed initiation of antibiotic treatment are important risk factors for renal scarring. The management of VUR depends on multiple factors and may include surveillance only or antimicrobial prophylaxis; very few patients with VUR need surgical correction. Patients with renal scarring should be monitored for hypertension and those with significant scarring should also be monitored for proteinuria and chronic kidney disease.

BACKGROUND: Renal scarring is prominently observed in children with vesicoureteral reflux (VUR) and can lead to complicated renal outcomes. Although biopsy is the gold standard to detect renal scarring, it is an invasive procedure. There are established renal biomarkers which can help detect renal scarring. Individual biomarkers have not shown to have extensively good discriminatory ability for this.
OBJECTIVE: This paper aims at combining the values of multiple biomarkers in models to detect renal scarring.
METHODS: Secondary data with the values of renal biomarkers like kidney injury molecule-1, neutrophil gelatinase-associated lipocalin (NGAL), and urinary creatinine along with the renal scarring status was considered. Logistic regression, discriminant analysis, Bayesian logistic regression, Naïve Bayes, and decision tree models were developed with these markers. The discriminatory ability of individual biomarkers along with the models was assessed using the area under the curve from ROC curve. Sensitivity, specificity, and misclassification rates were estimated and compared.
RESULTS: NGAL was the most predominant renal biomarker in classifying the patients with renal scarring (AUC: 0.77 (0.67, 0.87); p value < 0.001). Each of the model performed better than individual biomarkers. Decision tree (AUC: 0.83 (0.74, 0.91); p value < 0.001) and Naïve Bayes model (misclassification rate = 20.2%) performed the best amongst the models.
CONCLUSIONS: Combining the values of renal biomarkers through a statistical or machine learning model to detect renal scarring is a better approach as compared to considering individual renal biomarkers.