Infant urinary tract infection in Sweden - A national study of current diagnostic procedures, imaging and treatment.

BACKGROUND: Urinary tract infection (UTI) in infants is a common, potentially life-threatening bacterial infection, and must be managed carefully through the entire chain of care from diagnosis, choice of treatment, follow-up and risk stratification of future complications. This Swedish nationwide study of infant UTI was conducted to evaluate the current management of infant UTI, yield of investigations and the Swedish UTI guidelines' ability to detect abnormalities of importance in the urinary tract. METHODS: Infants < 1 year with a first episode of UTI were included in a prospective multicenter study. Treatment and follow-up were provided by local pediatricians. Clinical and laboratory findings and imaging results were reported to the coordinating center. The current management and results were compared with a previous Swedish study. RESULTS: One thousand three hundred six infants were included. Urine sampling was performed with clean catch technique in 93% of patients. Initial oral antibiotic treatment was used in 63%, predominantly third generation cephalosporines. Permanent kidney abnormalities were found in 10% and dilating vesicoureteral reflux (VUR) in 8%. Higher rates of male gender, non-E. coli infection and ultrasound dilatation were seen in infants < 1 month. UTI recurrences were reported in 18%. CONCLUSIONS: Infant UTI is still generating a considerable amount of follow-up examinations. There is a significant shift towards clean catch as the main urine sampling method. Voiding cystourethrography is performed less frequently reducing the findings of low grade VUR. The incidence of renal scarring is comparable with earlier studies which suggests that the Swedish guidelines are able to identify individuals with risk for long-term complications.

Urodynamic Abnormalities in Children with Primary Bilateral Vesicoureteral Reflux.

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.

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.

First episode of febrile urinary tract infection in children, detection and risk factors of kidney scarring: A prospective cohort study.

AIMS: This prospective study aimed to evaluate the characteristics and findings of children who presented with acute pyelonephritis (APN) and to determine the independent risk factors for kidney scarring. MATERIAL AND METHODS: Patients who satisfied the following criteria were enrolled in the study: first known episode of APN; at least two of the following findings: fever ≥ 38.5 °C, white blood cell count ≥ 10,000/mm3, erythrocyte sedimentation rate ≥ 20 mm/h, C-reactive protein ≥ 20 mg/dL; absence of congenital abnormalities or other kidney and systemic diseases, except vesicoureteral reflux (VUR); no APN relapses until the time of kidney scar detection. 99mTc-Dimercaptosuccinic acid kidney scintigraphy (99mTc-DMSA) was performed at admission, along with a kidney ultrasound. Follow-up 99mTc-DMSA took place after 6 months. Radiographic cystourethrography for VUR detection and grading was performed 1 month after the acute infection. RESULTS: We enrolled 70 children in the study. The kidney ultrasound failed to diagnose more than half of the cases of APN. VUR was found in 21.5% of children. 75% had findings of APN in the acute phase through 99mTc-DMSA, while in the second 99mTc-DMSA, there was a complete remission in 68% of them. Scars were observed more frequently in older children, children with VUR grade ≥ III, and children not on antibiotic prophylaxis. CONCLUSION: VUR did not appear to be associated with the first episode of APN, and children older than 1 year of age had a higher risk of scarring. Antibiotic prophylaxis may prevent kidney scarring due to host immunomodulatory effects, but more studies are needed so that conclusions can be drawn.

Clinical implications of primary "occult" vesicoureteral reflux in male children.

OBJECTIVES: To compare characteristics and outcomes of vesicoureteral reflux (VUR) detected solely on isotopic cystography (IC) ("occult" VUR) with voiding cystourethrography (VCUG)-detected VUR. MATERIALS AND METHODS: Between 2015 and 2020, we retrospectively enrolled all male children first undergoing VCUG and, if negative, IC in the same session. Kidney injury (KI) was defined by abnormal estimated glomerular filtration rate and/or blood pressure and/or proteinuria. RESULTS: We enrolled 421 males with a median age of 3 months and a follow-up of 5.3 years. None exhibited KI initially, but 10% of those with VUR developed KI during follow-up. Two hundred and twenty-two patients (52.7%) did not show VUR, 152 (36.1%) had VCUG-diagnosed VUR, and 47 (11.2%) had occult VUR. Therefore, 47/199 patients (23.6%) with VUR had occult VUR. Among these, 34/47 (72.3%) had dilated VUR, and 22/47 (46.8%) exhibited split renal function < 45% and/or scar (scintigraphic damage). Compared to patients with occult VUR, those with VCUG-diagnosed VUR showed a similar prevalence of febrile urinary tract infection (fUTI) before and after VUR diagnostics and KI at the last follow-up but a higher prevalence of dilated VUR, of scintigraphic damage, and underwent surgery more frequently. At multiple logistic regression analysis, patients with VCUG-diagnosed VUR presented an increased risk of fUTI either before or after VUR diagnosis and of KI, while patients with occult VUR presented an increased risk of fUTI before (and among patients with dilated VUR also after) VUR diagnosis and of KI. CONCLUSION: Occult VUR affects 23.6% of male children with VUR with a non-negligible risk of VUR-associated KI and fUTI. IC could select, among males with recurrent fUTIs and negative VCUG, those requiring surgery for a possible dilated occult VUR. CLINICAL RELEVANCE STATEMENT: Vesicoureteral reflux may be overlooked in 25% of boys during VCUG, yet they are at risk of fUTIs and KI. In case of recurrent infections post-negative cystourethrography, IC could detect occult reflux, guiding surgical intervention.

[A Case of Neuropathic Lower Urinary Tract Dysfunction Due to Spina Bifida Occulta Discovered at the Age of 19 Years and Successfully Treated with Multidisciplinary Therapy].

A 19-year-old man had been aware of dysuria and urinary incontinence since childhood but did not seek medical attention. He was diagnosed with acute pyelonephritis due to lower urinary tract dysfunction associated with spina bifida occulta and tethered cord syndrome (TCS) due to spinal cord lipoma. After placement of a urethral catheter and antibacterial chemotherapy, the patient was cured of acute pyelonephritis. He was treated with solifenacin and started clean self-intermittent catheterization (CIC). Shortly after the start of CIC, the acute pyelonephritis flared up again, and he was managed with a reinserted urethral catheter until an untethering operation. Preoperative video urodynamics showed that the bladder morphology was Ogawa classification grade III with vesicoureteral reflux (VUR) at 92 ml infusion. With the combination of an untethering operation and additional mirabegron, the functional bladder capacity was increased to 353 ml and VUR improved, allowing for safe urinary management of the CIC. TCS can be diagnosed at any age and requires appropriate urinary management and therapeutic intervention as early as possible after diagnosis.

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

BACKGROUND: Vesico-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. METHODS: A 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. RESULTS: This 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). CONCLUSIONS: Although 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 STUDY: Observational Cohort-Study. LEVEL OF EVIDENCE: III.

[Kidney transplantation in children with complex urogenital malformations-what should be considered?] / Kindernierentransplantation bei komplexen urogenitalen Fehlbildungen ­ was gibt es zu beachten?

BACKGROUND: Congenital anomalies of the kidneys and urinary tract (CAKUT) are the most common cause of end-stage renal disease (ESRD) in children. Approximately one third of children with CAKUT have lower urinary tract dysfunction (LUTD). AIM: This article highlights the important aspects that need to be considered in kidney transplantation of children with complex urogenital malformations. MATERIALS AND METHODS: The paper reviews the existing literature regarding the evaluation, preparation, perioperative management, and follow-up of children with complex urogenital malformations and ESRD undergoing renal transplantation. RESULTS: Comprehensive diagnostics are required before any pediatric kidney transplantation. If LUTD is suspected, voiding cystourethrography and a urodynamic examination should be performed. Treatment of symptomatic vesicoureterorenal reflux and LUTD is mandatory prior to pediatric kidney transplantation. Following successful kidney transplantation of children with congenital urogenital malformations, lifelong follow-up is required. Regular reevaluations of the bladder by means of urodynamic examinations are necessary. In patients following bladder augmentation with intestinal segments or urinary diversions in childhood, regular endoscopic examinations of the urinary tract are recommended to rule out secondary malignancy. CONCLUSION: Treatment of children with complex urogenital malformations should be carried out in centers with appropriate expertise.

Case report: A novel compound heterozygous variant in the TNXB gene causes single kidney agenesis and vesicoureteral reflux.

Primary vesicoureteral reflux (VUR) is the prevailing congenital anomaly of the kidneys and urinary tract, posing a significant risk for pyelonephritis scarring and chronic renal insufficiency in pediatric patients. Nevertheless, the precise genetic etiology of VUR remains enigmatic. In this current investigation, we conducted whole-exome sequencing on a child exhibiting single kidney, devoid of any familial VUR background, along with both biological parents. Two missense variants (NM_019105.8: exon11: c.4111G>A and NM_019105.8: exon2: c.31A>T) in the TNXB gene were identified through whole-exome sequencing of the child. These variants were found to be inherited from the child's parents, with each parent carrying one of the variants. Molecular dynamics simulations were conducted to assess the impact of these variants on the tenascin XB proteins encoded by them, revealing varying degrees of impairment. Based on our findings, it is suggested that the TNXB compound heterozygous variant, consisting of c.4111G>A and c.31A>T, may be the underlying cause of right renal agenesis and left hydronephrosis in afflicted child. This discovery broadens the genetic range of the TNXB gene and establishes a genetic foundation for disease-specific preimplantation genetic diagnosis (PGD) in prospective pregnancies involving the parents of this afflicted child.

Management of Urinary Tract Infections and Vesicoureteric Reflux: Key Updates From Revised Indian Society of Pediatric Nephrology Guidelines 2023.

Non-specific symptoms and difficulty in collecting urine specimens make the diagnosis of urinary tract infection (UTI) challenging in children. However, timely diagnosis and initiation of therapy are essential to prevent complications. Children with recurrent UTIs require detailed evaluation and follow-up for optimal management. We report key updates from the revised evidence-based practice guidelines of the Indian Society of Pediatric Nephrology for UTIs and primary vesicoureteric reflux.