[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.

[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.

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.

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.

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.

Risk factors for new renal scarring in children with vesicoureteral reflux receiving continuous antibiotic prophylaxis.

To investigate the risk factors for new renal scarring (NRS) in children with vesicoureteral reflux (VUR) receiving continuous antibiotic prophylaxis (CAP). This was a single-center cohort study. The clinical data of 140 children with grade I-V VUR receiving CAP were analyzed. In this study, exposure variables were sex, younger age at the initial diagnosis of UTI ≤ 12 months, the occurrence of breakthrough urinary tract infection (BT-UTI), high-grade VUR, bilateral VUR, etiology, presence of renal scarring at the initial diagnosis and ultrasound abnormalities. The outcome was NRS. A total of 140 children were included in the risk factor analysis of NRS, 73 of whom experienced NRS, an incidence rate of 52.14%. Multivariate Cox regression suggested that the presence of renal function impairment after the initial diagnosis of UTI (OR 3.411, 95% CI 1.5751-6.646) and the occurrence of BT-UTI while receiving CAP (OR 1.995, 95% CI 1.089-2.958) were independent risk factors for NRS. Multivariate Cox regression showed that high-grade VUR had no significant effects on NRS (OR 0.940, 95% CI 0.462-1.912, P = 0.864). No significant difference was identified in multivariate Cox regression analysis in the IV-V group (vs I-III group) (OR 0.960, 95% CI 0.565-1.633, P = 0.960). Renal function impairment after the initial diagnosis of UTI and the occurrence of BT-UTI while receiving CAP were independent risk factors for NRS. Neither univariate analysis nor multivariate analysis found a correlation between VUR grade and NRS.

Antimicrobial prophylaxis for vesicoureteral reflux: which subgroups of children benefit the most?

BACKGROUND: While the Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) trial found that long-term antimicrobial prophylaxis reduced the risk of urinary tract infection (UTI) recurrences by 50%, 10 children had to be treated for one to benefit (i.e., observed number needed to treat (NNT) of 10). Accordingly, we re-analyzed RIVUR data to systematically identify subgroups of children with vesicoureteral reflux (VUR) with a smaller NNT. METHODS: Using patient-level data from the RIVUR trial, we applied penalized regression methods including the baseline age, VUR grade, type of index UTI, and bowel-bladder dysfunction (BBD) as covariates to identify subgroups. RESULTS: We identified four relevant subgroups of children that appear to benefit from long-term antimicrobial prophylaxis, all with observed NNTs smaller than or equal to 5: children with grade IV VUR, BBD, and febrile index UTI (1% of the sample), children with BBD and febrile index UTI (7% of the sample), children with BBD (12% of the sample), and children with grade IV VUR (8% of the sample). CONCLUSIONS: Use of long-term antimicrobial prophylaxis appears to be particularly relevant for children with BBD (and any grade of VUR) and those with grade IV VUR (regardless of BBD status). However, because details regarding the treatment of BBD are not available, further studies are needed to fully determine the role of prophylactic antimicrobials in the management of children with VUR who have BBD.

Role of dexamethasone in controlling the proinflammatory cytokine cascade in the first episode of paediatric acute pyelonephritis.

AIM: Febrile urinary tract infection is a common bacterial infection in childhood. The kidney damage after acute pyelonephritis (APN) could be related to the stimulation of the proinflammatory response. We aimed to investigate the role of inflammatory cytokines and the effect of dexamethasone after a first episode of APN. METHODS: Subanalysis of the DEXCAR RCT in which children with confirmed APN (1 month-14 years) were randomly assigned to receive a 3 days course of either intravenous dexamethasone or placebo. Urinary cytokine levels at diagnosis and after 72 h of treatment were measured. RESULTS: Ninety-two patients were recruited. Younger patients, males and those with abnormalities in the ultrasound study or vesicoureteral reflux showed higher values of urinary cytokines. Patients with severe APN had higher Tumour Necrosis Factor (TNF)α levels (81.0 ± 75.8 vs. 33.6 ± 48.5 pg/mg creatinine, p = 0.015). Both intervention groups showed similar basal clinical characteristics, including urinary cytokine levels. Treatment reduced urinary cytokine levels irrespective of dexamethasone administration. Neither the intervention group nor the urinary cytokine levels modulated the development of kidney scars. CONCLUSION: Basal urinary cytokines were associated with age, abnormal ultrasound and vesicoureteral reflux. Patients with severe APN had higher TNFa urinary levels. Administration of dexamethasone in children with APN does not improve the control of the proinflammatory cytokine cascade.

Longitudinal follow-up of bladder function in children who participated in the Swedish Reflux Trial.

BACKGROUND: Several publications have reported the coexistence of vesicoureteral reflux (VUR) and bladder dysfunction in children. Whether this dysfunction remains in the longer term is not yet known. OBJECTIVE: This study revisited children who participated in the Swedish Reflux Trial (SRT) with the primary aim of evaluating whether bladder and bowel dysfunction (BBD) in these patients persisted until adolescence. The secondary aim was to evaluate two BBD subgroups, and relations to recurrent urinary tract infections (UTI). STUDY DESIGN: Of the 161 eligible children at SRT study-end, 73 children participated. Their bladder function was evaluated longitudinally using a validated BBD questionnaire with symptom score (cut-off ≥7) and uroflowmetry, at five (T2) and ten years (T3) after study-end. T1 was the SRT study-end. Besides BBD, the sub-diagnoses overactive bladder (OAB) and dysfunctional voiding symptoms (DVS) were calculated from symptom scores. RESULTS: BBD was diagnosed in 37% of children at mean age 3.7 years, which decreased with age to 23% of adolescents (mean age 15.7). DVS and OAB subgroups were equally common at T1, but only DVS was identified at the last follow-up (T3) (p = 0.0008). Recurrent UTIs were seen in 17% at T3 and were more common in patients with BBD (p = 0.038). The gender distribution of BBD also changed, from being equally common at the end of the SRT to affecting mainly adolescent girls at the last follow-up (p = 0.022). Information was available regarding VUR status after repeat VCUGs during follow-up in 22 patients, 12 of them after endoscopic treatment. An improvement in VUR grade was found in the 22, but during follow-up numbers with BBD or UTI did not differ between treated and non-treated groups. DISCUSSION: The prevalence of BBD decreased from 37% at 3-4 years of age to 23% in adolescence, when it was almost exclusively seen in girls. BBD and the subgroup DVS were associated with UTI. Even if epidemiological studies have established a predisposition to bladder symptoms and UTI in girls, little is known about bladder function in adolescents with a history of VUR during the first years of life. One limitation of the study was the number of patients participating. Also, the number of patients with kidney damage was more common in the cohort. CONCLUSION: In this longitudinal follow-up of BBD in children with VUR, the number of children with BBD decreased with age. In adolescence, both BBD and recurrent UTIs mainly affected girls.

Preoperative and Intraoperative Urine Cultures and Its Association With Postoperative Infection After Ureteroneocystostomy.

OBJECTIVE: To unveil this association, we hypothesize that preoperative and intraoperative urinary tract infection (UTI) will be correlated with postoperative UTI and sepsis occurrence. PATIENTS AND METHODS: The 2020 National Surgical Quality Improvement Program Pediatric (NSQIP-P) data was analyzed for patients undergoing ureteroneocystostomy (UNC) for vesicoureteral reflux (VUR). Patients that underwent UNC for treatment of VUR with urine culture obtained within 2weeks preoperatively or on the day of surgery were identified. The patients were divided into 3 groups: no bacterial growth, bacterial growth with UTI, and bacterial growth polymicrobial growth. Patient demographics and preoperative variables were evaluated. RESULTS: The postoperative urinary tract infection rate of the three groups were 2.0%, 9.2%, and 9.9% for group A, B, C, respectively (P < .001). Postoperative sepsis was noted to be 0.5%, 1.3%, and 3.6% for group A, B, C (P < .01). Additionally, there was a difference between mean operative time (P < .001), mean length of stay (P = .03), and mean days from operation to discharge (P < .01). On adjusted analysis, both groups B and C had higher rates of UTI compared to group A. Group C was also seen to have greater rates of sepsis on adjusted analysis. CONCLUSION: The association found between preoperative UTI with less than 2 species of microorganisms (group B) and postoperative UTI indicates that UTI treatment and antibiotic prophylaxis should be considered when undergoing UNC for VUR. The results of this study may lead to more careful consideration of the use of preoperative and intraoperative urine culture as well as treatment of UTI in pediatric patients with VUR undergoing UNC.