Vantris vs. deflux for treatment of paediatric vesicoureteral reflux: Efficacy and obstruction risk.

INTRODUCTION: The aim was to compare the efficacy of polyacrylate polyalcohol copolymer (PPC) injections and dextranomer/hyaluronic acid (Dx/Ha) injections for the endoscopic treatment of vesicoureteral reflux in children. MATERIAL: This retrospective cohort study included 189 young patients who had endoscopic treatment for vesicoureteral reflux from January 2012 to December 2019 in our center. Among them, 101 had PCC injections and 88 had Dx/Ha injections. Indications for treatment were vesicoureteral reflux with breakthrough urinary tract infection or vesicoureteral reflux with renal scarring on dimercaptosuccinic acid (DMSA) renal scan. Endoscopic injection was performed under the ureteral meatus. Early complications, recurrence of febrile urinary tract infection and vesicoureteral reflux after endoscopic injection, ureteral obstruction and reintervention were evaluated and compared between groups. RESULTS: Endoscopic treatment was successful in 90.1% of patients who had PPC injection and in 82% of patients who had Dx/Ha injection. Four patients presented a chronic ureteral obstruction after PPC injection, one with a complete loss of function of the dilated kidney. One patient in the Dx/Ha group presented a postoperative ureteral dilatation after 2 injections. CONCLUSION: Despite a similar success rate after PPC and Dx/Ha injections for endoscopic treatment of VUR, there may be a greater risk of postoperative ureteral obstruction after PPC injections. The benefit of using PPC to prevent febrile UTI and renal scarring in children with low-grade VUR does not seem to outweigh the risk of chronic ureteral obstruction.

GEN1 as a risk factor for human congenital anomalies of the kidney and urinary tract.

BACKGROUND: Congenital anomalies of the kidney and urinary tract (CAKUT) are prevalent birth defects. Although pathogenic CAKUT genes are known, they are insufficient to reveal the causes for all patients. Our previous studies indicated GEN1 as a pathogenic gene of CAKUT in mice, and this study further investigated the correlation between GEN1 and human CAKUT. METHODS: In this study, DNA from 910 individuals with CAKUT was collected; 26 GEN1 rare variants were identified, and two GEN1 (missense) variants in a non-CAKUT group were found. Mainly due to the stability results of the predicted mutant on the website, in vitro, 10 variants (eight CAKUT, two non-CAKUT) were selected to verify mutant protein stability. In addition, mainly based on the division of the mutation site located in the functional region of the GEN1 protein, 8 variants (six CAKUT, two non-CAKUT) were selected to verify enzymatic hydrolysis, and the splice variant GEN1 (c.1071 + 3(IVS10) A > G) was selected to verify shear ability. Based on the results of in vitro experiments and higher frequency, three sites with the most significant functional change were selected to build mouse models. RESULTS: Protein stability changed in six variants in the CAKUT group. Based on electrophoretic mobility shift assay of eight variants (six CAKUT, two non-CAKUT), the enzymatic hydrolysis and DNA-binding abilities of mutant proteins were impaired in the CAKUT group. The most serious functional damage was observed in the Gen1 variant that produced a truncated protein. A mini-gene splicing assay showed that the variant GEN1 (c.1071 + 3(IVS10) A > G) in the CAKUT group significantly affected splicing function. An abnormal exon10 was detected in the mini-gene splicing assay. Point-mutant mouse strains were constructed (Gen1: c.1068 + 3 A > G, p.R400X, and p.T105R) based on the variant frequency in the CAKUT group and functional impairment in vitro study and CAKUT phenotypes were replicated in each. CONCLUSION: Overall, our findings indicated GEN1 as a risk factor for human CAKUT.

Neonatal jaundice is associated with increased risks of congenital anomalies of the kidney and urinary tract and concomitant urinary tract infection.

The link between neonatal jaundice and urinary tract infection (UTI) remains debated, with congenital kidney and urinary tract anomalies (CAKUT) potentially playing a role. This population-based study aimed to analyze the correlations between neonatal jaundice, CAKUT, and concomitant UTI. The study cohort consisted of 2,078,122 live births from 2004 to 2014. We linked several population-based datasets in Taiwan to identify infants with unexplained neonatal jaundice and their mothers. The primary outcome was the rate of CAKUT occurring within 3 years after delivery, and the presence of concomitant UTI during neonatal jaundice hospitalization. Infants with neonatal jaundice had a significantly higher risk of CAKUT (adjusted odds ratio [aOR] 1.24, 95% confidence interval [CI] 1.11-1.39) during early childhood. Among the subtypes of CAKUT, obstructive uropathy, vesicoureteral reflux and other CAKUT were associated with an increased risk of neonatal jaundice. Infants who underwent intensive phototherapy, had a late diagnosis (> 14 days of postnatal age) or underwent a prolonged duration of phototherapy (> 3 days) exhibited a higher risk of concomitant UTI compared to other infants with jaundice. Our findings indicate a notable association between neonatal jaundice and increased risks of UTIs in the context of CAKUT. This study underscore the importance of vigilant monitoring and timely interventions for neonates presenting with jaundice, while acknowledging the complexity and variability in the progression of CAKUT and its potential connection to UTIs.

Voiding cystourethrography in patients undergoing endoscopic decompression of duplex system ureteroceles: to do or not to do?

OBJECTIVE: To assess the role of voiding cystourethrography (VCUG) in patients with duplex system ureterocele (DSU) undergoing endoscopic decompression (ED). MATERIALS AND METHODS: This is a retrospective study of 75 consecutive patients with DSU undergoing ED [median (range) age, 6 (1-148) months]. Patients were divided into 3 groups, 33 with a VCUG showing vesicoureteral reflux (VUR) before ED (VUR-group), 22 with a VCUG negative for VUR (No-VUR-group), and 20 who did not undergo a VCUG (No-VCUG-group). Secondary surgery (SS) rate was compared among groups. RESULTS: Groups were comparable for baseline characteristics. SS rate was 82% (27/33) in VUR-group vs. 32% (7/22) in the No-VUR-group (p = 0.0001), and 25% (5/20) in the No-VCUG-group (p = 0.001 vs. VUR-group, and 1 vs. No-VUR-group). In the VUR-group, 9 patients underwent preemptive endoscopic treatment of VUR during ED and SS rate was 44% (4/9) vs. 96% (23/24) in the remainder, p= 0.003. In the No-VCUG-group, a VCUG was performed during follow-up in 9/15 patients and showed reflux in all, although only 2 of these developed a (single) urinary tract infections. CONCLUSIONS: SS rate was significantly higher in patients with preoperative VUR. Instead, it was not significantly different between patients without VUR and those who did not undergo a VCUG before ED, despite all the latter who underwent a VCUG during follow-up had evidence of VUR generally in the absence of symptoms. In our opinion, a VCUG could be limited to patients developing symptoms after ED. If a VCUG is performed before ED, a preemptive treatment of VUR should be taken into consideration.

How effective is nephrectomy in curing hypertension in children with unilateral poorly functioning kidney? A systematic review.

PURPOSE: Some children with hypertension (HTN) have unilateral poorly functional kidney (PFK). This provides an opportunity for the clinician to cure the HTN by removal of the PFK, thereby avoiding the problems of long-term medication. However, there is sparse data in children regarding the effect of PFK nephrectomy on curing HTN. In this review, we analysed the etiology of PFK causing HTN and the effectiveness of nephrectomy in curing HTN in children. METHODS: We searched the databases to identify papers between January 2000 to December 2020 pertaining to children with PFK and HTN who underwent nephrectomy. Outcome analyzed was the resolution of HTN following nephrectomy. Duplicate publications, review articles and incomplete articles were excluded. Meta-analysis of heterogeneity was reported with I2statistics. Forest plot was constructed to compare the pooled prevalence of HTN resolution. RESULTS: Five articles with 88 patients were included. Majority (43%) of PFK were due to the unilateral atrophic kidney with or without vesicoureteral reflux (VUR); ureteropelvic junction obstruction and multicystic dysplastic kidney together accounted for 35% of cases and renovascular pathology for 22% of cases. With a follow-up of 1.5 to 3.3 years, nephrectomy was effective to cure HTN in 65.9% (95% CI 55-75%) children. CONCLUSIONS: In children with HTN and a unilateral PFK, nephrectomy cured the HTN in two-thirds of children. Unilateral atrophic kidney due to VUR was the most common cause of PFK. An increase in the utilisation of laparoscopy was observed in recent publications, hence laparoscopic nephrectomy may be considered a first choice of treatment in these children.

Single-port plus one in pediatric robotic-assisted Lich-Gregoir ureteral reimplantation for vesicoureteral reflux, a comparative analysis with short-term outcomes.

OBJECTIVE: To observe the safety and short-term outcomes of a new way of laparoscopic trocar placement in pediatric robotic-assisted Lich-Gregoir ureteral reimplantation for vesicoureteral reflux. METHODS: The retrospective study included 32 patients under 14 years diagnosed with primary vesicoureteral reflux (VUR). All these patients underwent robotic-assisted Lich-Gregoir ureteral reimplantation in our department from December 2020 to August 2022. These patients were divided into the following groups according to the different ways of trocar placement: 13 patients in group single-port plus one (SR) and 19 patients in group multiple-port (MR). Patients' characteristics as well as their perioperative and follow-up data were collected and evaluated. RESULTS: There was no significant difference in the data regarding patients' characteristics and preoperative data. These data included the grade of vesicoureteral reflux according to the voiding cystourethrogram (VCUG), and the differential degree of renal function (DRF) at the following time points: preoperative, postoperative, and comparison of preoperative and postoperative. There was no difference between the two groups. During surgery, the time of artificial pneumoperitoneum establishment, ureteral reimplantation time, and total operative time in the SR group were longer than those in the MR group. Yet only the time of artificial pneumoperitoneum establishment shows a statistical difference (P < 0.0001). Also, the peri-operative data, including the volume of blood loss, fasting time, hospitalization, and length of time that a ureteral catheter remained in place, and the number of postoperative complications demonstrate no difference. In addition, the SFU grade and VCUG grade at the following time point also show no difference between the two groups. CONCLUSION: The study demonstrates that SR in robotic-assisted Lich-Gregoir ureteral reimplantation has reached the same surgical effects as MR. In addition, the single-port plus one trocar placement receives a higher cosmetic satisfaction score from parents and did not increase the surgical time and complexity.

Gestational diabetes mellitus induces congenital anomalies of the kidney and urinary tract in mice by altering RET/MAPK/ERK pathway.

Gestational diabetes mellitus (GDM) presents a substantial population health concern. Previous studies have revealed that GDM can ultimately influence nephron endowment. In this study, we established a GDM mouse model to investigate the embryological alterations and molecular mechanisms underlying the development of congenital anomalies of the kidney and urinary tract (CAKUT) affected by GDM. Our study highlights that GDM could contribute to the manifestation of CAKUT, with prevalent phenotypes characterized by isolated hydronephrosis and duplex kidney complicated with hydronephrosis in mice. Ectopic ureteric buds (UBs) and extended length of common nephric ducts (CNDs) were noted in the metanephric development stage. The expression of Ret and downstream p-ERK activity were enhanced in UBs, which indicated the alteration of RET/MAPK/ERK pathway may be one of the mechanisms contributing to the increased occurrence of CAKUT associated with GDM.

Update on imaging recommendations in paediatric uroradiology: the European Society of Paediatric Radiology workgroup session on voiding cystourethrography.

Voiding cystourethrography (VCUG) is a fluoroscopic technique that allows the assessment of the urinary tract, including the urethra, bladder, and-if vesicoureteral reflux (VUR) is present-the ureters and the pelvicalyceal systems. The technique also allows for the assessment of bladder filling and emptying, providing information on anatomical and functional aspects. VCUG is, together with contrast-enhanced voiding urosonography (VUS), still the gold standard test to diagnose VUR and it is one of the most performed fluoroscopic examinations in pediatric radiology departments. VCUG is also considered a follow-up examination after urinary tract surgery, and one of the most sensitive techniques for studying anatomy of the lower genitourinary tract in suspected anatomical malformations. The international reflux study in 1985 published the first reflux-protocol and graded VUR into five classes; over the following years, other papers have been published on this topic. In 2008, the European Society of Paediatric Radiology (ESPR) Uroradiology Task Force published the first proposed VCUG Guidelines with internal scientific society agreement. The purpose of our work is to create a detailed overview of VCUG indications, procedural recommendations, and to provide a structured final report, with the aim of updating the 2008 VCUG paper proposed by the European Society of Paediatric Radiology (ESPR). We have also compared VCUG with contrast-enhanced VUS as an emergent alternative. As a result of this work, the ESPR Urogenital Task Force strongly recommends the use of contrast-enhanced VUS as a non-radiating imaging technique whenever indicated and possible.

[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.

Clinical efficacy of laparoscopic Lich-Gregoir versus transvesicoscopic Cohen reimplantation for ureterobladder junction malformations in children.

OBJECTIVE: To assess the clinical efficacy of laparoscopic Lich-Gregoir (LLG) and transvesicoscopic Cohen reimplantation (TCR) in the treatment of vesicoureteral junction obstruction (VUJO) and vesicoureteral reflux (VUR). METHODS: This study retrospectively analyzed the clinical data of 66 pediatric patients with VUJO and VUR. They were classified into two groups, undergoing either the laparoscopic Lich-Gregoir operation (LLGO) (n = 35) or transvesicoscopic Cohen reimplantation operation (TCRO) (n = 31). The surgeries were performed between April 2018 and September 2022 at the First Affiliated Hospital of Guangxi Medical University, China. General characteristics, preoperative attributes, postoperative complications, renal function recovery, and improvement of hydronephrosis were compared between the two groups. RESULTS: All surgical procedures were successful with no requirement for reoperation. Both groups were comparable with respect to gender, affected side, weight, and postoperative complications. Nonetheless, the LLGO group contained a greater number of children younger than 12 months. The LLGO group demonstrated superiority over the TCRO group regarding the duration of the operation, intraoperative blood loss, and length of postoperative hospital stay. In contrast, postoperative complications, recovery of renal function, and hydronephrosis improvement did not exhibit statistically significant differences between the two groups. CONCLUSION: Both LLGO and TCRO were demonstrated to be precise, safe, and reliable surgical methods for treating pediatric VUJO and VUR. LLGO ureteral reimplantation offers particular advantages in selecting cases and appears more suitable for children younger than 12 months who have a small bladder capacity.

Laparoscopic and Robot-assisted Laparoscopic Reimplantation for Lower Ureter Pathology. A Multi-institutional Comparative Study in 1343 Patients.

OBJECTIVE: To evaluate the outcomes of children with vesicoureteral reflux (VUR) and obstructive megaureter (OM) utilizing various laparoscopic and robot-assisted approaches. MATERIALS AND METHODS: Retrospective review of all pediatric laparoscopic and robot-assisted cases for lower ureter pathology was performed between 2016-2022 in 13 academic centers worldwide. Five surgical approaches were assessed: LEUR, LVCUR, LDECUR, RALUR, and RADECUR. RESULTS: One thousand three hundred forty-three patients (490 boys and 853 girls) with a median age of 30 months (IQR 12-63) were treated at 13 centers. Nine hundred and eight patients (68%) underwent reimplantation due to VUR (unilateral in 818 and bilateral in 90 patients). Four hundred thirty-five (32%) had a surgery due to ureterovesical junction (UVJ) obstruction. Mean length of follow-up was 14 months (IQR 8-33). Median operative time was 202 minutes (IQR 142-220) in the robotic arm compared to 240 minutes (IQR 160-267) in the laparoscopic (P = .45). Intracorporeal excisional tapering was performed in 118 (8%) of the patients. Six patients in the OM group required additional surgery due to progressive obstruction. In the VUR group, 84% underwent voiding cystourethrography postoperatively. 5.6% showed residual reflux. Grade 1-2 Clavien-Dindo complications occurred in 10 patients (0.7%) and 6 (0.4%) in the laparoscopic and robotic arm, respectively. Grade 3 complications occurred in 17 (1.2%) and 8 (0.5%) in both arms, respectively. Surgical success was achieved in 96% of patients. CONCLUSION: Laparoscopic and robot-assisted laparoscopic approaches are simple, safe, and effective for treating all grades of VUR and OM. Robot-assisted approach is beneficial in terms of operative time, intracorporeal suturing, and lower complications rate.

Frequency of Treatment Failure of UTIs in Children With Congenital Urinary Tract Anomalies.

OBJECTIVES: Children with certain congenital anomalies of the kidney and urinary tract and neurogenic bladder (CAKUT/NGB) are at higher risk of treatment failure for urinary tract infections (UTIs) than children with normal genitourinary anatomy, but the literature describing treatment and outcomes is limited. The objectives of this study were to describe the rate of treatment failure in children with CAKUT/NGB and compare duration of antibiotics between those with and without treatment failure. METHODS: Multicenter retrospective cohort of children 0 to 17 years old with CAKUT/NGB who presented to the emergency department with fever or hypothermia and were diagnosed with UTI between 2017 and 2018. The outcome of interest was treatment failure, defined as subsequent emergency department visit or hospitalization for UTI because of the same pathogen within 30 days of the index encounter. Descriptive statistics and univariates analyses were used to compare covariates between groups. RESULTS: Of the 2014 patient encounters identified, 482 were included. Twenty-nine (6.0%) of the 482 included encounters had treatment failure. There was no difference in the mean duration of intravenous antibiotics (3.4 ± 2.5 days, 3.5 ± 2.8 days, P = .87) or total antibiotics between children with and without treatment failure (10.2 ± 3.8 days, 10.8 ± 4.0 days, P = .39) Of note, there was a higher rate of bacteremia in children with treatment failure (P = .04). CONCLUSIONS: In children with CAKUT/NGB and UTI, 6.0% of encounters had treatment failure. Duration of antibiotics was not associated with treatment failure. Larger studies are needed to assess whether bacteremia modifies the risk of treatment failure.

A preliminary study of the miRNA restitution effect on CNV-induced miRNA downregulation in CAKUT.

BACKGROUND: The majority of CAKUT-associated CNVs overlap at least one miRNA gene, thus affecting the cellular levels of the corresponding miRNA. We aimed to investigate the potency of restitution of CNV-affected miRNA levels to remediate the dysregulated expression of target genes involved in kidney physiology and development in vitro. METHODS: Heterozygous MIR484 knockout HEK293 and homozygous MIR185 knockout HEK293 cell lines were used as models depicting the deletion of the frequently affected miRNA genes by CAKUT-associated CNVs. After treatment with the corresponding miRNA mimics, the levels of the target genes have been compared to the non-targeting control treatment. For both investigated miRNAs, MDM2 and PKD1 were evaluated as common targets, while additional 3 genes were investigated as targets of each individual miRNA (NOTCH3, FIS1 and APAF1 as hsa-miR-484 targets and RHOA, ATF6 and CDC42 as hsa-miR-185-5p targets). RESULTS: Restitution of the corresponding miRNA levels in both knockout cell lines has induced a change in the mRNA levels of certain candidate target genes, thus confirming the potential to alleviate the CNV effect on miRNA expression. Intriguingly, HEK293 WT treatment with investigated miRNA mimics has triggered a more pronounced effect, thus suggesting the importance of miRNA interplay in different genomic contexts. CONCLUSIONS: Dysregulation of multiple mRNA targets mediated by CNV-affected miRNAs could represent the underlying mechanism behind the unresolved CAKUT occurrence and phenotypic variability observed in CAKUT patients. Characterizing miRNAs located in CNVs and their potential to become molecular targets could eventually help in understanding and improving the management of CAKUT.