Mechanosensitive Piezo1 channels promote neurogenic bladder fibrosis via regulating TGF-ß1/smad and Hippo/YAP1 pathways.

Bladder fibrosis is the final common pathway of neurogenic bladder (NB), and its underlying mechanisms are not fully understood. The current study aims to evaluate the involvement of Piezo1, a mechanosensitive channel, in bladder fibrosis. A full-thickness bladder specimen was taken during ileocystoplasty or ureteral reimplantation from the surgical cut's edge. By chopping off the bilateral lumbar 6 (L6) and sacral 1 (S1) spinal nerves, NB rat models were produced. Utilizing both pharmacological inhibition and Piezo1 deletion, the function of Piezo1 in the TGF-ß1-induced fibrosis model of SV-HUC-1 cells was delineated. RNA-seq, immunofluorescence, immunohistochemistry (IHC), and Western blotting were used to evaluate the degrees of fibrosis and biochemical signaling pathways. Piezo1 protein expression was noticeably elevated in the human NB bladder. The abundance of Piezo1 protein in bladder of NB rats was significantly increased. RNA-seq analysis revealed that the ECM-receptor interaction signaling pathway and collagen-containing ECM were increased in spinal cord injury (SCI)-induced bladder fibrosis. Moreover, the bladder of the NB rat model showed activation of YAP1 and TGF-ß1/Smad. In SV-HUC-1 cells, siRNA suppression of Piezo1 led to profibrotic responses and activation of the TGF-ß1/Smad pathway. However, Yoda1, a Piezo1-specific agonist, significantly reduced these effects. TGF-ß1 increased Piezo1 activation and profibrotic responses in SV-HUC-1 cells. In the TGF-ß1-induced fibrosis model of SV-HUC-1 cells, the TGF-ß1/Smad pathway was activated, whereas the Hippo/YAP1 signal pathway was blocked. Inhibition of Piezo1 further prevented this process. Piezo1 is involved in the progression of NB bladder fibrosis and profibrotic alterations in SV-HUC-1 cells, likely through regulating the TGF-ß1/Smad and Hippo/YAP1 pathways.

A Pilot Study of the Effect of Transcutaneous Spinal Cord Stimulation on Micturition-Related Brain Activity and Lower Urinary Tract Symptoms After Stroke.

PURPOSE: Transcutaneous spinal cord stimulation (TSCS) is a novel neuromodulation modality developed to promote functional restoration in patients with neurological injury or disease. Previous pilot data suggest that lower urinary tract dysfunction (LUTD) due to stroke may be partially alleviated by TSCS. In this study, we examine the mechanism of this effect by evaluating bladder-related brain activity in patients before and after TSCS therapy and comparing it to healthy volunteers. MATERIALS AND METHODS: Patients who developed storage LUTD after a stroke and healthy volunteers without LUTD were recruited. Patients and healthy volunteers underwent simultaneous urodynamics and functional MRI. Patients then completed 24 biweekly sessions of TSCS and underwent another simultaneous urodynamics-functional MRI study. Clinical outcomes were assessed using validated questionnaires and voiding diary. RESULTS: Fifteen patients and 16 healthy volunteers completed the study. Following TSCS, patients exhibited increased blood-oxygen-level-dependent activity in areas including periaqueductal grey, the insula, the lateral prefrontal cortex, and motor cortex. Prior to TSCS therapy, healthy controls exhibited higher blood-oxygen-level-dependent activity in 17 regions, including multiple regions in the prefrontal cortex and basal ganglia. These differences were attenuated after TSCS with no frontal brain differences remaining between healthy volunteers and stroke participants who completed therapy. Neuroimaging changes were complemented by clinically significant improvements in questionnaire scores and voiding diary parameters. CONCLUSIONS: TSCS therapy modulated bladder-related brain activity, reducing differences between healthy volunteers and stroke patients with LUTD. These changes, alongside improved clinical outcomes, suggest TSCS as a promising approach for LUTD management.

Quality of Life and Bladder Symptoms in Adolescents and Young Adults With Spina Bifida Who Catheterize via Urethra vs Catheterizable Channel.

PURPOSE: We sought to assess associations between health-related quality of life (QOL), bladder-related QOL, bladder symptoms, and bladder catheterization route among adolescents and young adults with spina bifida. MATERIALS AND METHODS: Clinical questionnaires administered to individuals ≥ 12 years old requiring catheterization between June 2019 to March 2020 in a spina bifida center were retrospectively analyzed. Questionnaires were completed in English or Spanish independently or with caregiver assistance. Medical records were reviewed for demographic and clinical characteristics. Primary exposure was catheterization route (urethra or channel). Primary outcome was health-related QOL, measured by Patient-Reported Outcomes Measurement Information System Pediatric Global Health 7 (PGH-7). Secondary outcomes were bladder-related QOL and bladder symptoms, measured by Neurogenic Bladder Symptom Score (NBSS). Nested, multivariable linear regression models assessed associations between catheterization route and questionnaire scores. RESULTS: Of 162 patients requiring catheterization, 146 completed both the PGH-7 and NBSS and were included. Seventy-three percent were catheterized via urethra and 27% via channel. Median age was 17.5 years (range 12-31), 58% of patients were female, and 80% had myelomeningocele. Urinary incontinence was more common among those who catheterized via urethra (60%) compared to channel (33%). On adjusted analyses, catheterization route was not significantly associated with PGH-7 or NBSS bladder-related QOL scores. More bladder symptoms were associated with worse bladder-related QOL. Patients who catheterized via channel had fewer bladder symptoms than those who catheterized via urethra. CONCLUSIONS: Catheterization route was not significantly associated with QOL. Though catheterization via channel was associated with fewer bladder symptoms, only degree of current bladder symptoms was significantly associated with bladder-related QOL.

Identifying Bladder Phenotypes After Spinal Cord Injury With Unsupervised Machine Learning: A New Way to Examine Urinary Symptoms and Quality of Life.

PURPOSE: Patients with spinal cord injuries (SCIs) experience variable urinary symptoms and quality of life (QOL). Our objective was to use machine learning to identify bladder-relevant phenotypes after SCI and assess their association with urinary symptoms and QOL. MATERIALS AND METHODS: We used data from the Neurogenic Bladder Research Group SCI registry. Baseline variables that were previously shown to be associated with bladder symptoms/QOL were included in the machine learning environment. An unsupervised consensus clustering approach (k-prototypes) was used to identify 4 patient clusters. After qualitative review of the clusters, 2 outcomes of interest were assessed: the total Neurogenic Bladder Symptom Score (NBSS) and the NBSS-satisfaction question (QOL). The NBSS and NBSS-satisfaction question at baseline and after 1 year were compared between clusters using analysis of variance and linear regression. RESULTS: Among the 1263 included participants, the 4 identified clusters were termed "female predominant," "high function, low SCI complication," "quadriplegia with bowel/bladder morbidity," and "older, high SCI complication." Using outcome data from baseline, significant differences were observed in the NBSS score, with the female predominant group exhibiting worse bladder symptoms. After 1 year, the overall bladder symptoms (NBSS Total) did not change significantly by cluster; however, the QOL score for the high function, low SCI complication group had more improvement (ß = -0.12, P = .005), while the female predominant group had more deterioration (ß = 0.09, P = .047). CONCLUSIONS: This study demonstrates the utility of machine learning in uncovering bladder-relevant phenotypes among SCI patients. Future research should explore cluster-based targeted strategies to enhance bladder-related outcomes and QOL in SCI.

Substantial incidence of bladder dysfunction in patients with VACTERL association: Implications for surveillance.

VACTERL association is defined as the nonrandom co-occurrence of a minimum of three of the following six key components: Vertebral anomalies, Anal atresia, Cardiac malformations, Tracheo-Esophageal fistula, Renal anomalies, and Limb abnormalities. Patients presenting with two components may also belong in the same spectrum. Additional components have been associated with VACTERL defects, including single umbilical artery, tethered spinal cord (TSC), and genital malformations. We observed a significant proportion of patients with bladder dysfunction (often called neurogenic bladder in the medical record) when reviewing a cohort of patients with VACTERL defects at our clinical center. Our finding calls attention to bladder dysfunction as an additional VACTERL phenotypic component. The prevalence of bladder dysfunction is greatest in those with genital anomalies, anorectal malformations, sacral dysplasia, renal anomalies, and TSC. We propose that patients with two or more VACTERL malformations be monitored for symptoms of bladder dysfunction if one or more of the identified risk factors are present until the achievement of urinary continence.

Genetic Contributions to Lower Urinary Tract Dysfunction.

Lower urinary tract dysfunction (LUTD) can manifest as a spectrum of voiding symptoms in childhood, including urinary urgency, frequency, hesitancy, and incontinence. In severe cases, it can lead to frequent urinary tract infections, hydronephrosis, kidney scarring, and chronic kidney disease. Non-neurogenic neurogenic bladder (NNNB) is a diagnosis of exclusion in which children develop discoordination between the detrusor smooth muscle and external urethral sphincter in the absence of neurological or obstructive lesions, resulting in severe LUTD. Historically, such disorders of voiding were thought to result from behavioral maladaptation. However, it is now increasingly recognized that some individuals may have an underlying genetic etiology for their symptoms. Here, we performed exome sequencing for five probands with NNNB or other forms of severe LUTD, and we identified two individuals with monogenic etiologies for their symptoms. One individual had a homozygous exon 9 deletion in HPSE2 and another had a homozygous single amino acid deletion (p.Gly167del) in ARL6. We performed PCR experiments to identify the breakpoints of the HPSE2 exon 9 deletion and implicate microhomology-mediated end joining as a potential mechanism by which the deletion arose. These findings suggest that genetic testing should be considered for children with severe LUTD.

A robot-assisted laparoscopic revision of an artificial urinary sphincter in a patient with spinal cord injury.

This step-by-step article demonstrates our approach to robot-assisted laparoscopic revision of a bladder neck sited artificial urinary sphincter (AUS) for a spinal cord injured patient. The bladder neck location of an AUS in the spinal cord injured demographic is ideal to minimise urethral complications and urinary tract infections, whilst the transabdominal approach reduces the risk of wound breakdown that can occur via the typical perineal incision for AUS insertion. The accompanying video will guide viewers as to our minimally invasive technique for cuff revision in the event of secondary surgery for recurrent urinary incontinence.

An individual participant meta-analysis of mirabegron in multiple sclerosis and spinal cord injury.

INTRODUCTION: Our objective was to conduct an individual patient data meta-analysis (IPDMA) of the two published randomized placebo-controlled trials of mirabegron in people with neurogenic lower urinary tract dysfunction (NLUTD) due to spinal cord injury (SCI) or multiple sclerosis (MS). METHODS: We identified two randomized, placebo-controlled trials. We extracted individual patient data from the trials and evaluated two primary outcomes: change in maximum cystometric capacity and change in the patient perception of bladder condition (PPBC). We also evaluated several secondary outcomes related to urodynamic function and quality of life. We conducted three exploratory analyses to test hypotheses based on our clinical experiences with mirabegron in NLUTD. Analysis of covariance with adjustment for baseline values was used for the statistical analysis. RESULTS: Our IPDMA included 98 patients from the two trials. The results showed that mirabegron was associated with a significant improvement in maximum cystometric capacity (+41 mL, p = 0.04) and in the PPBC (-0.8, p < 0.01) compared to placebo. Secondary outcomes including peak neurogenic detrusor overactivity pressure (-20 cm H2O, p < 0.01), incontinence-QOL score (+12, p < 0.01), and 24 h pad weights (-79 g, p = 0.04) also improved significantly compared to placebo. Exploratory analyses found similar improvements in people with MS and SCI; some outcomes improved to a greater degree among people with incomplete SCI, or SCIs that were below T7. CONCLUSIONS: Our IPDMA provides evidence supporting the use of mirabegron in patients with NLUTD due to SCI or MS. Further work evaluating differential responses in people with different SCI lesion characteristics may be warranted.

Impact of patient position on cystometric parameters in pediatric patients with neurogenic bladder: A prospective study.

AIMS: Urodynamic studies (UDSs) play a crucial role in evaluating lower urinary tract function in pediatric patients with neurogenic bladder. However, the influence of patient position on urodynamic parameters in this population remains understudied. This study aims to investigate the effect of patient position on urodynamic results in children with neurogenic bladder. METHODS: A prospective study was conducted with 50 pediatric patients diagnosed with neurogenic bladder. Urodynamic recordings were obtained during a single session, with the first two fillings in the supine position and the third filling in the sitting position. Urodynamic parameters assessed included detrusor overactivity (DO), maximum detrusor pressure (MDP), cystometric bladder capacity (CBC), compliance (C), detrusor leak point pressure (DLPP), and bladder volume at the moment of incontinence (DLPV). RESULTS: Patient position did not significantly influence CBC, DO, C, and DLPV (p > 0.05). However, there were significant differences in MDP and DLPP between the supine and sitting positions (p < 0.05), with higher values observed in the supine position. CONCLUSIONS: These findings highlight the importance of considering the patient's position when interpreting urodynamic results and making treatment decisions for children with neurogenic bladder. The higher MDP and DLPP values in the supine position may have clinical implications for assessing upper urinary tract integrity and treatment planning. However, further research is needed to understand the underlying mechanisms and generalize these findings to broader patient populations.

Why are continent catheterizable channels continent? A stomal pressure profilometry feasibility study.

INTRODUCTION: A continent catheterizable channel (CCC) may be a solution for patients with impaired bladder emptying and difficult transurethral access. Leakage of the CCC is a common complication. To prevent leakage, the pressure in the CCC has to be higher than the reservoir (bladder/pouch) pressure in at least one location. It has not been clearly defined through which mechanism(s) the CCC achieves continence. In this feasibility study, we measured the CCC pressure profile in adult patients with various types of CCC's with and without stomal leakage. METHODS: Adult patients with a CCC on a (augmented) bladder or pouch who underwent a urodynamic investigation between January and March 2023 were included. Next to the standard urodynamic investigation, a continuous stomal pressure measurement (CSP) and stomal pressure profilometry with empty bladder (SPP-1) and with filled bladder (SPP-2) of the CCC were performed. RESULTS: A total of 17 patients were included. It was technically possible to perform SPP-1 and SPP-2 in all patients, and to measure the CSP in 16/17 patients. The median maximum stomal pressures in SPP-1 and SPP-2 were 112 (interquartile range [IQR], 76-140) cmH2O and 120 (IQR, 92-140) cmH2O, respectively. Nine patients had stomal leakage during the urodynamic investigation. In five patients, the detrusor leak point pressure (dLPP) was low (<20 cmH2O). A pressure peak at the beginning of SPP-2 was absent in all patients with stomal leakage at low dLPP. CONCLUSION: SPP and CSP measurement in CCCs are feasible. We found differences in SPP-2 between patients with and without leakage at low dLPP, indicative of a role of the intravesical tunnel in continence or high dLPP. The results of this study may improve our understanding of the physiology and dynamics of CCCs as well as the management of CCC-related complications.

Effectiveness and patient perspective on the use of intravesical gentamicin instillations to treat recurrent urinary tract infections in neurogenic lower urinary tract dysfunction.

INTRODUCTION: Patients with neurogenic lower urinary tract dysfunction (NGLUTD) who require catheterization either with clean intermittent catheters (CIC) or indwelling catheters suffer with frequent urinary tract infections (UTIs). This study assessed the efficacy, patient persistence, satisfaction, and the impact on quality of life (QoL) of gentamicin nightly bladder instillations with 15 mg. METHODS: This is a prospective survey of 36 patients with NGLUTD and recurrent UTIs prescribed long-term gentamicin to prevent UTIs. Eligible patients completed a questionnaire about their use and satisfaction with gentamicin therapy, as well as survey questionnaires to address QoL. A retrospective chart review was also performed to obtain medical history, confirm drug persistence, and obtain accurate UTI data for the 12 months preceding and after starting instillations. RESULTS: The rate of laboratory proven symptomatic UTI requiring antibiotic treatment decreased from 3.9 to 1.1 infections per year with no increase in antibiotic resistance and no significant side effects reported by patients. Eight patients stopped therapy before a full year for various reasons, but the remaining 72% of patients have continued to use the therapy now with a mean of 4.2 years later. Satisfaction among those continuing the medication was very high. CONCLUSION: Gentamicin bladder instillations with 15 mg nightly in patients with indwelling catheters or CIC with NGLUTD are very effective and safe with high patient satisfaction. This therapy can be maintained long-term with continued efficacy.

Success Rate and Predicting Factors for Repeated High-Dose Intradetrusor Dysport Injections in Children With Neurogenic Bladder: A Retrospective Study.

OBJECTIVES: Evaluating the effectiveness and safety of repeated high-dose intradetrusor abobotulinumtoxin A (Dysport®) injections for the treatment of pediatric neurogenic bladders refractory to medications. DESIGN: Retrospective interventional study. PARTICIPANTS: The cohort included 37 children (22 boys and 15 girls) of median age 9.2 years. Inclusion criteria were diagnosis of neurogenic bladder and failure to respond to medical treatment. Exclusion criteria were augmented bladder, insufficient data, and interval of > 11 months between video-urodynamic study and Dysport injection. INTERVENTIONS: All participants were treated with an intra-detrusor injection of Dysport 30 IU/kg (up to 1000 IU) under general anesthesia. Repeated (second and third) injections were scheduled (6-12 months) in patients who demonstrated an improvement in cystometric parameters. All participants underwent video urodynamic testing before onset of treatment and 4-5 months after subsequent injection. MAIN OUTCOME MEASURES: Success of treatment was defined as a decrease in end filling pressure (EFP) to < 40 cm H2O and/or a 20% increase in maximal cystometric capacity (MCC). These parameters along with initial bladder features were evaluated for ability to predict treatment success. RESULTS: No side effects of Dysport were observed or reported. The overall success rate was 62%. MCC increased by a median of 30% (IQR 200-300, p < 0.001), 37% (IQR 197-310, p = 0.001) and 45% (IQR 245-300, p = 0.025) after the first, second and third injections, respectively. Median EFP decreased from 45 cm H2O to 34 cm H2O (IQR 20-45, p = 0.029), 23 cm H2O (IQR 20-37, p = 0.004), and 20 cm H2O (IQR 12-32, p = 0.049) after the first, second, and third injections, respectively. No predicting factor of success of treatment were found; However, three of five cases of "end stage" bladder showed improvement. CONCLUSIONS: High-dose Dysport injection is safe and effective for the treatment of neurogenic bladder. Studies with larger cohort and a control group would further elucidate which bladders would benefit most. At present, we recommend treating also bladders with "end stage" features with botulinum toxin before considering augmentation.

The rationale for bladder washouts in children with neurogenic bladder.

Children with a neurogenic bladder are at risk of developing recurrent urinary tract infections and long-term kidney failure. Due to an altered lower urinary tract, children may be overtreated for simple bacteriuria or undertreated for a potentially severe urinary tract infection. This group of patients represent high users of healthcare, and are at risk of colonization and development of antibiotic resistance. Bladder washouts with non-antibiotic electrochemically activated solutions are a potential new prophylactic option for patients with bladder dysfunction when clean intermittent catheterization has resulted in chronic bacteriuria.

Improvement of neurogenic urinary dysfunctions in female rats treated with an injection of botulinum toxin A at the epicenter of the spinal cord injured site.

OBJECTIVE: To assess the effect of an injection of botulinum toxin A (BoNT/A) at the epicenter of the spinal cord injury (SCI) site on the recovery of lower urinary tract function in female rats with thoracic SCI. MATERIALS AND METHODS: Twenty-four female Wistar rats with Sham (laminectomy at T8/T9 level) or SCI (at T8/T9; 30 g compression for 5 s) were assigned into Sham-SS (injected with 5 µL of saline solution), Sham-BoNT/A (injected with 15 pg/rat, equivalent to 7.5 Units/kg of BoNT/A in 5 µL volume), SCI-SS (injured and injected with saline), SCI-BoNT/A (injured and injected with BoNT/A), N = 6 per group. Weekly evaluation of stereotyped micturition behavior, hind-limb nociception, and locomotor activity was performed 1 week before and during 6 weeks after surgery. Subsequently, all groups underwent simultaneous electromyography of the external urethral sphincter (EUS-EMG) and cystometric (CMG) studies. RESULTS: A compression SCI at the T8/T9 thoracic level significantly impairs sensory and locomotive functions, as well as stereotyped micturition behavior. However, these impairments were improved by BoNT/A injection after SCI. Neither injections of saline solution nor BoNT/A had an appreciable effect on the same parameters evaluated in the Sham groups. The combined EUS-EMG and CMG evaluations revealed important improvements of lower urinary tract physiology, particularly a reduction in the frequency of non-voiding contractions and the properties of EUS bursting activity indicated as the amplitude of the EUS-EMG signal and duration of burst electrical activity during effective voiding. CONCLUSION: The severe impairments on sensory and locomotive functions as well stereotyped micturition caused by an SCI could be potentially attenuated by an injection of a small amount of BoNT/A directly into the epicenter of the SCI region. A reduction in the release of neurotoxic neurotransmitters requiring the SNARE complex may be the mechanism triggered by BoNT/A to reduce neurotoxicity and hyperexcitability created in the SCI area to improve the survival of spinal cord cells involved in micturition.

Bladder management is the top health concern among adults with a spinal cord injury.

INTRODUCTION AND OBJECTIVE: Individuals with spinal cord injury (SCI) commonly experience secondary complications though it is not known how they prioritize these different health domains. Using the Neurogenic Bladder Research Group (NBRG) SCI registry, our objective was to identify the top health concerns of individuals with SCI and identify factors that may be associated with these choices with particular focus on urologic issues that participants face. METHODS: Participants in the NBRG registry were asked: "What are the top 3 problems that affect you on a daily basis?" Urinary symptoms and QoL were assessed with the Neurogenic Bladder Symptom Score (NBSS). Multivariate regression was used to identify factors related to selecting a top ranked health issue. RESULTS: Among our 1461 participants, 882 (60.4%) were men and the median age was 45.1 years (IQR 25.3-64.9). Bladder management was the most commonly top ranked primary issue (39%) followed by pain (16.4%) and bowel management (11.6%). Factors associated with ranking bladder management as the primary concern included years since injury (OR 1.01 [1.00-1.02], p = 0.042), higher (worse) total NBSS (OR 1.05 [1.03-1.06], p < 0.001), and higher (worse) NBSS QoL (OR 1.25 [1.12-1.41], p < 0.001). Reporting chronic pain on a daily basis was associated with ranking pain as the primary health concern (OR 41.7 [15.7-170], p < 0.001). CONCLUSIONS: In this cohort, bladder management was ranked as the top health issue and increasing time from injury was associated with increased concern over bladder management. More bladder symptoms were also associated with ranking bladder management as a primary concern while bladder management method and urinary tract infections rate were not.

Development and Testing of the Spinal Cord Injury Bladder and Bowel Control Questionnaire (SCI-BBC-Q).

INTRODUCTION: Recovery of lower urinary tract (LUT) and lower gastrointestinal tract (LGIT) is a high priority for people with lived experience following spinal cord injury (SCI). A universally accepted validated patient-reported outcome (PRO) measure of the individual sensory and motor components of LGIT and LUT function, which allows tracking of recovery is lacking. To address this literature gap, the SCI Bladder and Bowel Control Questionnaire (SCI-BBC-Q) was developed. METHODS: The SCI-BBC-Q was developed as a direct assessment of the micturition and defecation experiences of an individual with SCI with possible neurogenic LUT and LGIT dysfunction. The SCI-BBC-Q development process consisted of two phases, measure development and evaluation. Measure development was guided by a conceptual framework, review of existing instruments and literature, and an iterative process of item incorporation, review, feedback, and consensus revision. Evaluation included cognitive interviewing, and assessments of feasibility, reliability, and content validity. RESULTS: The final 6-item SCI-BBC-Q is a PRO, which assesses motor and sensory function related to micturition and defecation, requiring ~5 min to complete. Assessments of clarity of the instrument components with regard to understanding of what is being asked in the questionnaire, feasibility of administration, reliability, internal consistency, and agreement with proxy measures have demonstrated that the SCI-BBC-Q provides consistent, stable, and reproducible data. Significant correlations were found between SCI-BBC-Q scores and the anorectal motor and sensory components of the International Standards for the Neurological Classification of SCI. CONCLUSION: The SCI-BBC-Q is a practical and reliable method for baseline and ongoing evaluation of patients with neurogenic LUT and LGIT dysfunction, especially in the acute and subacute period when function is changing due to neurological plasticity. It is also appropriate for use in monitoring response to treatments related to neurological recovery.

Urinary biomarkers in children with neurogenic and non-neurogenic lower urinary tract dysfunction: A systematic review and meta-analysis.

AIM: The aim of this systematic review is to assess urinary biomarkers studied in children with neurogenic and non-neurogenic lower urinary tract dysfunction (LUTD). MATERIALS AND METHODS: The systematic review was conducted in accordance with the PRISMA guidelines. The screening was performed on PUBMED without any publication date limitation. Only original articles were included. Parameters related to the following topics were obtained: study design, characteristics of participants, number of participants, age, control group, types of biomarkers, measurement technique in urine, subgroup analysis, urodynamic findings, and outcome. Dutch Cochrane Checklist (DCC) and level of evidence by EBRO platform were used for quality assessment. Meta-analysis was performed with the Comprehensive Meta-Analysis Version 4 program. RESULTS: A total of 494 studies were screened and 16 studies were included. 11 (68.75%) were conducted in children with non-neurogenic LUTD and 5 (31.25%) neurogenic LUTD. Nerve growth factor (NGF) was evaluated in 12 studies, brain-derived neurotrophic factor (BDNF) in 5, Tissue Inhibitor of Metalloproteinase-2 (TIMP-2) in 2, transforming growth factor beta-1 (TGF Beta-1) in 2, neutrophil gelatinase-associated lipocalin (NGAL) in 1, and Aquaporin-2 in 1. According to DCC, 10 (62.5%) articles were evaluated on 4 (37.5%) items and 4 articles on 5 items. The average score was 3.91+/-0.56. The level of evidence was found as B for 13 (81.25%) articles and C for 3 (18.75%). In meta-analysis, urinary NGF levels in children with non-neurogenic LUTS were significantly higher than in the healthy control group (Hedges's g = 1.867, standard error = 0.344, variance = 0.119, p = 0.0001). CONCLUSION: Urinary biomarkers are promising for the future with their noninvasive features. However, prospective studies with larger sample sizes are needed to better understand the potential of urinary biomarkers to reflect urodynamic and clinical findings in children with LUTD.

Effects of posterior tibial nerve stimulation (PTNS) on lower urinary tract dysfunction: An umbrella review.

BACKGROUND: Lower urinary tract dysfunction (LUTD) is a common, troublesome condition that often negatively affects patients' quality of life. Current literature has long been interested in how posterior tibial nerve stimulation (PTNS) can affect this condition. AIM: To extensively and systematically explore how PTNS affects LUTD based on the most recent systematic reviews. METHODS: A systematic search was conducted in PubMed, Scopus, Web of Science, and Embase according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. All the systematic reviews, with or without meta-analysis that assessed the effects of PTNS on LUTD were retrieved. The quality of the included studies was assessed using the Joanna Briggs Institute tool, and analysis was conducted using the Comprehensive Meta-Analysis version 3 tool. RESULTS: From a total of 3077 citations, 20 systematic reviews entered this study, and 13 of them included meta-analysis. The population of studies varied vastly, for instance, some studies included only children or women while other focused on a specific pathology like multiple sclerosis-induced neurogenic LUTD. The majority of included studies reported an overall improvement in LUTD following percutaneous PTNS, although admitting that these results were derived from moderate to low-quality evidence. CONCLUSION: The findings of this thorough umbrella review showed that the positive benefits of PTNS in treating LUTD are currently supported by low-quality evidence, and it is crucial to interpret them with great care.

Characteristics and predictors of chronic kidney disease in children with myelomeningocele: a nationwide cohort study.

BACKGROUND: Myelomeningocele (MMC) is highly prevalent in developing countries, and MMC-related neurogenic bladder is an important cause of childhood chronic kidney disease (CKD). This nationwide study aimed to evaluate demographic and clinical features of pediatric patients with MMC in Turkey and risk factors associated with CKD stage 5. METHODS: Data from children aged 0-19 years old, living with MMC in 2022, were retrospectively collected from 27 pediatric nephrology centers. Patients > 1 year of age without pre-existing kidney abnormalities were divided into five groups according to eGFR; CKD stages 1-5. Patients on dialysis, kidney transplant recipients, and those with eGFR < 15 ml/min/1.73 m2 but not on kidney replacement therapy at time of study constituted the CKD stage 5 group. RESULTS: A total of 911 (57.8% female) patients were enrolled, most of whom were expectantly managed. Stages 1-4 CKD were found in 34.3%, 4.2%, 4.1%, and 2.4%, respectively. CKD stage 5 was observed in 5.3% of patients at median 13 years old (range 2-18 years). Current age, age at first abnormal DMSA scan, moderate-to-severe trabeculated bladder on US and/or VCUG, and VUR history were independent risk factors for development of CKD stage 5 (OR 0.752; 95%; CI 0.658-0.859; p < 0.001; OR 1.187; 95% CI 1.031-1.367; p = 0.017; OR 10.031; 95% CI 2.210-45.544; p = 0.003; OR 2.722; 95% CI 1.215-6.102; p = 0.015, respectively). Only eight CKD stage 5 patients underwent surgery related to a hostile bladder between 1 and 15 years old. CONCLUSION: MMC-related CKD is common in childhood in Turkey. A proactive approach to neurogenic bladder management and early protective surgery in selected cases where conservative treatment has failed should be implemented to prevent progressive kidney failure in the pediatric MMC population in our country.

Is body composition important in the context of renal function in pediatric neurogenic bladder?

BACKGROUND: Neurogenic bladder due to myelomeningocele (MMC) is a significant risk factor for chronic kidney disease in children. Cystatin C (CysC) is a more accurate GFR marker than creatinine as it is unaffected by muscle mass but may be influenced by fat mass and BMI. This study evaluates: (1) GFR measurement accuracy using CysC and creatinine in MMC-related neurogenic bladder, (2) the relationship between body composition via bioelectrical impedance analysis (BIA) and renal parameters, and (3) the use of BIA for non-invasive GFR and body composition assessment. METHODS: Forty children (median age 9.96 years) underwent serum creatinine, CysC testing, and BIA measurements. We assessed age, sex, spinal lesion level, anthropometric measurements, BMI, and activity using Hoffer's scale. GFR was calculated using five creatinine-based formulas, three CysC-based, and three combining CysC and creatinine, including BIA GFR as an alternative approach. RESULTS: Creatinine-based GFR estimates were significantly higher than CysC-based GFR. Although only 30% of MMC patients met the traditional BMI criteria for overweight/obesity, 62.5% were obese based on BIA-measured body fat percentage. Significant differences were found in CysC and CysC-based GFR equations within BMI and fat mass groups. Positive correlations were observed between CysC and body weight, BMI percentiles, body fat mass and fat-to-muscle ratio. Muscle mass positively correlated with creatinine. CONCLUSIONS: BIA-determined fat mass percentage is a more sensitive obesity indicator than BMI in MMC patients. CysC levels and CysC-based GFR equations are influenced by body fat mass, requiring consideration of adiposity to avoid misestimating renal impairment.