Genetic determinants of renal scarring in children with febrile UTI.

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.

Obesity and febrile urinary tract infection in young children.

BACKGROUND: Obesity is a risk factor for infectious diseases. However, the relationship between obesity and febrile urinary tract infection (fUTI) is controversial. This study aimed to determine the relationship between obesity and fUTI in young children. METHODS: We analyzed the medical records of children aged <2 years who were admitted to our hospital because of fever between April 2013 to March 2018. The children were categorized into three groups of non-obese, overweight, and obese according to the World Health Organization weight-for-length curves for children aged <2 years. RESULTS: A total of 600 patients were enrolled in this study, of whom 118 were diagnosed with first fUTI. Patients in the fUTI group were younger than those in the control group (patients who were diagnosed with other febrile diseases) (5 ± 5.11 vs 11 ± 6.53 months; P < 0.001). There were no significant differences in the populations of overweight and obese children between the fUTI and control groups. In the fUTI group, the duration of fever, types of pathogen, recurrent rate, the grades of vesicoureteral reflux, and renal scarring were not associated with obesity. The white blood cell count and C-reactive protein levels were not significantly different among the three weight-for-length categories. The same results were obtained when the fUTI group was compared with an age-matched control group (n = 192, 4 ± 2.55 months old; P = 0.261). CONCLUSIONS: Obesity is not a significant risk factor for fUTI in febrile hospitalized young children. Our study suggests that conducting urinalysis for febrile young children without obvious sources, irrespective of obesity, should be considered.

Neutrophil-Macrophage Imbalance Drives the Development of Renal Scarring during Experimental Pyelonephritis.

BACKGROUND: In children, the acute pyelonephritis that can result from urinary tract infections (UTIs), which commonly ascend from the bladder to the kidney, is a growing concern because it poses a risk of renal scarring and irreversible loss of kidney function. To date, the cellular mechanisms underlying acute pyelonephritis-driven renal scarring remain unknown. METHODS: We used a preclinical model of uropathogenic Escherichia coli-induced acute pyelonephritis to determine the contribution of neutrophils and monocytes to resolution of the condition and the subsequent development of kidney fibrosis. We used cell-specific monoclonal antibodies to eliminate neutrophils, monocytes, or both. Bacterial ascent and the cell dynamics of phagocytic cells were assessed by biophotonic imaging and flow cytometry, respectively. We used quantitative RT-PCR and histopathologic analyses to evaluate inflammation and renal scarring. RESULTS: We found that neutrophils are critical to control bacterial ascent, which is in line with previous studies suggesting a protective role for neutrophils during a UTI, whereas monocyte-derived macrophages orchestrate a strong, but ineffective, inflammatory response against uropathogenic, E. coli-induced, acute pyelonephritis. Experimental neutropenia during acute pyelonephritis resulted in a compensatory increase in the number of monocytes and heightened macrophage-dependent inflammation in the kidney. Exacerbated macrophage-mediated inflammatory responses promoted renal scarring and compromised renal function, as indicated by elevated serum creatinine, BUN, and potassium. CONCLUSIONS: These findings reveal a previously unappreciated outcome for neutrophil-macrophage imbalance in promoting host susceptibility to acute pyelonephritis and the development of permanent renal damage. This suggests targeting dysregulated macrophage responses might be a therapeutic tool to prevent renal scarring during acute pyelonephritis.

Prevalence of renal scaring caused by urinary tract infections in children: a systematic review and meta-analysis.

PURPOSE. SOURCES OF INFORMATION: Urinary tract infection (UTI) is the second most common infection in children, the most important complication of which is renal scarring. The aim of present study was to evaluate the prevalence of renal scarring after UTI in children through systematic review and meta-analysis. METHODS: The international databases of Science Direct, PubMed, Scopus, and Web of Science and the Google Scholar search engine were searched using standard keywords. The sources found were from 2010 to 2020 and the search stage was updated until 2021.02.16. Data were analyzed using STATA-14 software and the significance level was considered at P<0.05. RESULTS: In 29 studies with a sample size of 9,986 children, the prevalence of renal scarring in children was estimated at 35% (95% CI: 29-41). Also, the prevalence of renal scarring was in girls 61% (95% CI: 40-81) and in boys 34% (95% CI: 11-57). The prevalence of unilateral renal scarring in children was 56% (95% CI: 48-65) and bilateral renal scarring was 31% (95% CI: 14-48). In addition, the prevalence of scar was 54% in children with reflux and 12% in children without vesicoureteral reflux. CONCLUSIONS: More than one third of people under the age of 18 after UTI have renal scarring. The prevalence of this complication in girls is about 2 times higher than that in boys and in people with reflux, it is about 4 times higher than people who do not have urinary reflux. Also, about half of people under the age of 18 suffer from unilateral renal scarring and about one third of them suffer from bilateral renal scarring.

Vesicoureteral reflux is it important to find?

Vesico-ureteral reflux (VUR) has long been recognized as associated with urinary tract infections (UTIs), renal scarring, and chronic kidney disease (CKD). The concept of "reflux nephropathy" was born, whereby the VUR was considered the culprit, predisposing to recurrent UTIs and providing a conduit whereby the infection could ascend to the kidneys resulting in scarring and destruction. The more severe grades of reflux were thought to place the young child at particular risk of CKD. The question being asked in this pro/con debate is whether VUR is indeed the culprit responsible for a significant proportion of children with CKD, a number of whom progress to end-stage kidney failure (ESKF), and is thus important to find and treat, or is it an innocent bystander associated with CKD and ESKF but not the cause. We believe the latter and will present convincing evidence supported by large scale prospective randomized controlled trials that VUR is not the ogre it was thought to be and is not important to find following a UTI (with some exceptions).

MR-Proadrenomedullin as biomarker of renal damage in urinary tract infection in children.

BACKGROUND: Midregional-proadrenomedullin (MR-proADM) is a useful prognostic peptide in severe infectious pathologies in the adult population. However, there are no studies that analyze its utility in febrile urinary tract infection (fUTI) in children. An accurate biomarker would provide an early detection of patients with kidney damage, avoiding other invasive tests like renal scintigraphy scans. Our objective is to study the usefulness of MR-proADM as a biomarker of acute and chronic renal parenchymal damage in fUTI within the pediatric population. METHODS: A prospective cohort study was conducted in pediatric patients with fUTI between January 2015 and December 2018. Plasma and urine MR-proADM levels were measured at admission in addition to other laboratory parameters. After confirmation of fUTI, renal scintigraphy scans were performed during the acute and follow-up stages. A descriptive study has been carried out and sensitivity, specificity and ROC curves for MR-proADM, C-reactive protein, and procalcitonin were calculated. RESULTS: 62 pediatric patients (34 female) were enrolled. Scintigraphy showed acute pyelonephritis in 35 patients (56.5%). Of those patients, the median of plasmatic MR-proADM (P-MR-proADM) showed no differences compared to patients without pyelonephritis. 7 patients (11.3%) developed renal scars (RS). Their median P-MR-proADM levels were 1.07 nmol/L (IQR 0.66-1.59), while in patients without RS were 0.48 nmol/L (0.43-0.63) (p < 0.01). The AUC in this case was 0.92 (95% CI 0.77-0.99). We established an optimal cut-off point at 0.66 nmol/L with sensitivity 83.3% and specificity 81.8%. CONCLUSION: MR-ProADM has demonstrated a poor ability to diagnose pyelonephritis in pediatric patients with fUTI. However, P-MR-proADM proved to be a very reliable biomarker for RS prediction.

Vitamin D deficiency as a risk factor for renal scarring in recurrent urinary tract infections.

BACKGROUND: Renal scarring is a serious complication in recurrent urinary tract infections (UTIs). Vitamin D deficiency has also been reported to be a risk factor for UTIs although, to date, no association between vitamin D deficiency and renal scarring has yet been identified. In the present study, it was investigated whether vitamin D deficiency may be a risk factor for renal scarring in patients with recurrent UTIs. METHODS: The study included patients between the ages of 1 and 18 years who were admitted to the pediatric nephrology department of the center between November 1, 2018 and November 1, 2019 and who were diagnosed with recurrent UTIs. The medical records of the patients were reviewed for the collection of demographic data, vitamin D levels, ultrasonography results and scintigraphic investigations with 99m-technetium dimercaptosuccinic acid (99m Tc-DMSA). The patients were divided into two groups: those with and without renal scarring, diagnosed via 99m Tc-DMSA. The vitamin D levels and other parameters of the two groups were compared. RESULTS: Vitamin D deficiency (<20 ng/mL) was observed in 73.9% of the patients without renal scarring, and in 94.1% of those with renal scarring (P = 0.015). A logistic regression analysis revealed vitamin D deficiency to be an independent risk factor for renal scarring in patients with recurrent UTIs (OR = 0.796 [0.691-0.917]). CONCLUSIONS: Vitamin D deficiency is found to be a risk factor for renal scarring in patients with recurrent UTIs. Vitamin D treatment may contribute to the prevention of renal scarring in patients with recurrent UTI.

"Point of no return" in unilateral renal ischemia reperfusion injury in mice.

BACKGROUND: In the past years evidence has been growing about the interconnection of chronic kidney disease and acute kidney injury. The underlying pathophysiological mechanisms remain unclear. We hypothesized, that a threshold ischemia time in unilateral ischemia/reperfusion injury sets an extent of ischemic tubule necrosis, which as "point of no return" leads to progressive injury. This progress is temporarily associated by increased markers of inflammation and results in fibrosis and atrophy of the ischemic kidney. METHODS: Acute tubule necrosis was induced by unilateral ischemia/reperfusion injury in male C57BL/6 N mice with different ischemia times (15, 25, 35, and 45 min). At multiple time points between 15 min and 5 weeks we assessed gene expression of markers for injury, inflammation, and fibrosis, histologically the injury of tubules, cell death (TUNEL), macrophages, neutrophil influx and kidney atrophy. RESULTS: Unilateral ischemia for 15 and 25 min induced upregulation of markers for injury after reperfusion for 24 h but no upregulation after 5 weeks. None of the markers for inflammation or fibrosis were upregulated after ischemia for 15 and 25 min at 24 h or 5 weeks on a gene expression level, except for Il-6. Ischemia for 35 and 45 min consistently induced upregulation of markers for inflammation, injury, and partially of fibrosis (Tgf-ß1 and Col1a1) at 24 h and 5 weeks. The threshold ischemia time for persistent injury of 35 min induced a temporal association of markers for inflammation and injury with peaks between 6 h and 7 d along the course of 10 d. This ischemia time also induced persistent cell death (TUNEL) throughout observation for 5 weeks with a peak at 6 h and progressing kidney atrophy beginning 7 d after ischemia. CONCLUSIONS: This study confirms the evidence of a threshold extent of ischemic injury in which markers of injury, inflammation and fibrosis do not decline to baseline but remain upregulated assessed in long term outcome (5 weeks). Excess of this threshold as "point of no return" leads to persistent cell death and progressing atrophy and is characterized by a temporal association of markers for inflammation and injury.

URINARY EXCRETION OF TGF-Β1 AND VEGF IN CHILDREN WITH VESICOURETERAL REFLUX.

OBJECTIVE: The aim of this study was to investigate the relation between urinary TGF-ß1, urinary VEGF and renal scarring resulted from VUR. PATIENTS AND METHODS: Materials and methods: This study included 141 patients with VUR and 34 healthy sex and age matched children. The statistical analysis consisted of descriptive statistical parameters, KruskalWallis, Mann-Whitney tests and ROC analysis. RESULTS: Results: The urine levels of TGF-ß1 and VEGF were significantly increased in children with VUR, compared to the controls. The levels of TGF-ß1 urine excretion in children with renal scarring were higher compared children no renal scarring. The indicators of VEGF urine excretion in children with renal scarring compared to indicators in children no renal scarring, were lower, however exceeded the indicators in children of control group. The area under the ROC curve for TGF-ß1 was 109.9, for VEGF was 207.6. CONCLUSION: Conclusions: The study allowed to substantiate and propose non-invasive methods for early diagnosis of renal scarring in children with VUR.

Serum soluble ST2 as a marker of renal scar in pediatric upper urinary tract infection.

BACKGROUND AND OBJECTIVES: Upper urinary tract infection is the most common serious bacterial infection in childhood. Patients with upper urinary tract infection have a risk for renal scarring with subsequent complications including hypertension, proteinuria, and progressive renal failure. However, the predictive biomarkers of renal scarring in children with upper urinary tract infection are still unknown. In this study, we evaluated whether soluble ST2 levels can be biomarkers of subsequent renal scarring in patients with upper urinary tract infection. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: We retrospectively studied pediatric patients with upper urinary tract infection at a tertiary center. Twenty-eight children had an upper urinary tract infection with (n = 14) and without (n = 14) renal scarring and underwent 99mtechnetium dimercaptosuccinic acid imaging. In addition, 13 control subjects were enrolled. The clinical data and serum cytokine levels, including soluble ST2 levels, were compared between those with and without renal scars. RESULTS: Serum soluble ST2 levels were significantly higher in the scar group than in the non-scar group, whereas there was no difference in the levels of serum interferon-γ, interleukin-6, interleukin-10, soluble tumor necrosis factor receptor 1, and transforming growth factor-ß between the scar and non-scar groups. The area under the curve for differentiating between the non-scar and scar groups on the basis of measurements of serum soluble ST2 was 0.79, with a sensitivity and specificity of 92.9% and 64.3%, respectively. CONCLUSION: These results suggest that serum soluble ST2 levels on admission could be a useful biomarker of subsequent renal scarring in pediatric patients with upper urinary tract infection.

Intrarenal reflux, an overlooked entity - retrospective analysis of 1,166 voiding cysturethrographies in children.

BACKGROUND: The significance of intrarenal reflux as a risk factor for renal scarring and hypertension has been discussed. Fluoroscopic detection of intrarenal reflux depends on the equipment, the training of the radiologists and the timing of spot film acquisition. OBJECTIVE: To evaluate the prevalence of intrarenal reflux and its association with age, gender, grade of vesico-uretero-renal reflux and the renal segments affected. MATERIALS AND METHODS: We retrospectively analysed 1,166 voiding cysturethrographies. Patients' ages ranged from 1 day old to 19 years old. Vesico-uretero-renal reflux was detected in 209 female and 164 male patients using a standardised technique with digital pulsed fluoroscopy. The point in time and grade of reflux were documented with spot films. All radiographs showing reflux were assessed for the occurrence of intrarenal reflux. RESULTS: Intrarenal reflux was detected in 41 of 373 (11%) patients with vesico-uretero-renal reflux. Unilateral intrarenal reflux was found in 30 patients and bilateral in 11. The left kidney was more frequently affected than the right (31 versus 21). Only patients younger than 9 years of age were affected (mean age: 1.6 years, median: 0.8 years). Intrarenal reflux was independent of gender and was most frequently observed in grade IV reflux (59.6%) and less often in grade V (23.1%) and grade III (17.3%). CONCLUSION: Intrarenal reflux in this study was detected in 11% of patients with vesico-uretero-renal reflux, predominantly with reflux grade IV and in patients younger than 4 years old.

Urinary angiotensinogen in pediatric urinary tract infection.

BACKGROUND: Urinary tract infection (UTI) is one of the most common diseases in children, and urinary angiotensinogen (U-AGT) is a new biomarker gathering attention in many renal diseases. U-AGT reflects intrarenal renin-angiotensin system (RAS) activity. We conducted a study to measure U-AGT in children <4 months old with UTI. METHODS: All children <4 months old who came to Toshima Hospital with fever between January 2015 and December 2015 were included. Patients were divided into a UTI group and a non-UTI group, and U-AGT was measured. RESULTS: Median U-AGT was higher in patients with UTI compared with patients without UTI: (0.56 ng/dL, range, 0.025-2.753 ng/dL vs 0.13 ng/dL, range, 0.008-1.697 ng/dL, respectively; P < 0.05). CONCLUSIONS: U-AGT is elevated in UTI patients, and RAS activation may contribute to renal injury caused by UTI.

Antimicrobial misuse in pediatric urinary tract infections: recurrences and renal scarring.

BACKGROUND: In children, urinary tract infection (UTI) is one of a common bacterial infection. This study was conducted to detect the uropathogen, antimicrobial susceptibility, pathogen associated with recurrences and renal scarring in children initially taken care from general practitioners and later presented to tertiary care. METHODS: Every inward UTI episode, culture and antimicrobial susceptibility was done while on past 6-month, history of infections and use of antimicrobials was collected using clinical records and demonstration of antimicrobials. Children with recurrent pyelonephritis was followed and in vitro bio film formation was assessed. RESULTS: Frequency of UTI was significantly high among infants (p = 0.03). Last 6-month, all (220) were exposed to antimicrobials. Cefixime was the commonly prescribed antimicrobial (p = 0.02). In current UTI episode, 64.5% (142/220) of children with UTI were consulted GPs' prior to seek treatment from tertiary care pediatric unit (p = 0.02). While on follow up child who developed UTI, found urine culture isolates were significantly shifted from E. coli and K. pneumoniae to extended spectrum of beta-lactamase (ESBL) E. coli and K. pneumoniae. Out of 208 participants, 36 of them had re-current pyelonephritis (R-PN). Renal scarring (RS) was detected in 22 out of 70 patients with pyelonephritis following dimercaptosuccinic acid scan. Following each episodes of recurrent pyelonephritis 11% of new scar formation was detected (p = 0.02). Bio film forming E. coli and K. pneumoniae was significantly associated in patients with R-PN (p = 0.04). DISCUSSION: Medical care providers often prescribe antimicrobials without having an etiological diagnosis. While continuing exposure of third generation cephalosporin and carbapenem leads to development of ESBL and CRE microbes in great. The empiric uses of antimicrobials need to be stream lined with local epidemiology and antimicrobial susceptibility pattern. R-PN in childhood leads to RS. In great, bio film formation act as the focus for such recurrences.

Renal scarring and chronic kidney disease in children with spina bifida in a multidisciplinary Malaysian centre.

AIMS: The aim of this study was to determine the occurrence of renal cortical scarring and chronic kidney disease (CKD) in children with neurogenic bladder secondary to spina bifida (SB) managed at the Universiti Kebangsaan Malaysia Medical Centre. The secondary objective was to identify the clinical factors associated with these adverse outcomes. METHODS: The medical records of 56 children managed from 1997 were available. Socio-demographic and clinical data for SB children managed for a minimum of 2 years (n = 45) were reviewed. This included age at referral, gender, ethnicity, duration of care, type of SB lesion, presence of vesico-ureteric reflux (VUR), symptomatic urinary tract infections, bladder trabeculation, catheterisations and renal function. RESULTS: Forty-nine per cent of SB lesions were open myelomeningocoele, 40% were closed lesions and 11% were occult. Majority (96%) were at lumbar L3 or below. Twenty-nine children (64.5%) were referred before 6 months of age (mean15.8 months; range newborn to 125 months). Thirty-five (77.8%) had neurogenic bladder and 31(69%) had neurogenic bowel. Sixteen developed renal scarring and six, CKD. Late referral (≥6 months of age), small kidneys at referral, dilating VUR and bladder trabeculation were significant independent factors associated with scarring. On multivariate analysis, late referral (odds ratio (OR) 17.4; 95% confidence interval (CI) 1.26-238.7) and dilating VUR (OR 137.0; CI 6.4-2921.1) remained significant. CONCLUSION: Prevention of renal scarring and CKD remains a challenge in Malaysia even with multidisciplinary proactive care of SB children. Early referrals and more stringent management strategies for dilating VUR are still required.

Prophylactic antibiotics for children with recurrent urinary tract infections.

Prophylactic antibiotics for urinary tract infections are no longer routinely recommended. A large number of children must be given prophylaxis to prevent one infection and antibiotic resistance is a major concern when treating community-acquired urinary tract infections. The results of three recent significant studies are examined, with focus on the efficacy of prophylaxis, and recommendations are made.

La prophylaxie antibiotique n'est plus recommandée systématiquement en cas d'infections urinaires. Un grand nombre d'enfants doivent recevoir une prophylaxie pour prévenir une infection, et l'antibiorésistance est une préoccupation importante dans le traitement des infections urinaires d'origine communautaire. Les auteurs examinent les résultats de trois grandes études récentes, en s'attardant sur l'efficacité de la prophylaxie, et présentent des recommandations.

Long-term consequences of urinary tract infection in childhood: an electronic population-based cohort study in Welsh primary and secondary care.

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. AIM: To examine the association between childhood UTI and outcomes in an unselected population of children. DESIGN AND SETTING: A retrospective population-based cohort study using linked GP, hospital, and microbiology records in Wales, UK. METHOD: 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. CONCLUSION: 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.

Update and Summary of the European Association of Urology/European Society of Paediatric Urology Paediatric Guidelines on Vesicoureteral Reflux in Children.

BACKGROUND AND 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. KEY FINDINGS AND LIMITATIONS: 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 AND CLINICAL IMPLICATIONS: This summary of the updated 2023 EAU/ESPU guidelines provides practical considerations for the management and diagnostic evaluation of VUR in children. ADVANCING PRACTICE: 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. PATIENT SUMMARY: 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.

Approaches and Barriers to Biomarker Discovery: The Example of Biomarkers of Renal Scarring in Pediatric Urology.

A noninvasive test that can longitudinally assess renal parenchymal status would be incredibly valuable for a wide range of conditions, including neurogenic bladder, renal transplantation, and upper and lower urinary tract anomalies. To address this need, enormous amounts of time, effort, and resources have been invested to identify biologic molecules that signal the pathologic processes of renal parenchymal defects. In this comprehensive narrative review, the authors summarize biomarkers that have previously been investigated while highlighting the key pitfalls and barriers that have impeded biomarker discovery and translation.

Complete Remission of Renal Scarring in Follow-Up DMSA Renal Scintigraphy After 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.

Albuminuria is associated with 24-hour and night-time diastolic blood pressure in urinary tract infection with renal scarring.

BACKGROUND: We aimed to detect complications and associated risk factors in patients with renal scarring (RS) secondary to recurrent urinary tract infections (UTI). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.