Background Clean Intermittent Catheterization (CIC) is commonly used to manage urinary retention and lower urinary tract dysfunction in pediatric patients. Despite its widespread use, variability exists in how CIC education and support are delivered across clinical settings. This exploratory qualitative study aimed to examine current CIC education workflows, identify barriers and facilitators to care delivery, and inform future quality improvement efforts within a high-volume pediatric urology program. Methods Using an interpretive description approach within the exploratory phase of a broader quality improvement initiative, we conducted semi-structured interviews and focus groups with 16 healthcare providers and administrative staff involved in CIC education across pediatric urology care settings. Discussions explored CIC referral processes, scheduling workflows, teaching practices, follow-up approaches, and perceived barriers and facilitators to CIC education. Interviews were audio-recorded, transcribed verbatim and analyzed inductively using thematic analysis and workflow mapping. Results Workflow mapping identified substantial variability across referral, scheduling, teaching, and follow-up processes. Four major themes were identified: (1) referral and decision-making, (2) scheduling and pre-visit preparation, (3) CIC teaching encounter, and (4) post-teaching follow-up. Participants described challenges related to health literacy, interpreter integration, educational material accessibility, psychosocial complexity, and inconsistent coordination across care settings. Participants also identified opportunities to improve workflow consistency, communication, caregiver preparation, and follow-up support. Conclusion This CIC workflow assessment identified variability and key barriers influencing CIC education across pediatric care settings and highlighted opportunities for improvement. Findings informed development of a preliminary toolkit and quality improvement strategies including standardized workflows, pre-education materials, and patient- and caregiver-centered protocols to support adherence, experience, and outcomes.

Background Interstitial cystitis/bladder pain syndrome (IC/BPS) is a complex, chronic condition affecting the urinary bladder. Symptoms commonly associated with IC/BPS include painful urination, pain during intercourse, a persistent or recurrent sensation of bladder discomfort or pressure that often worsens as the bladder fills and eases after urination, urgency, frequent urination with little warning, nighttime urination disrupting sleep, and burning or other unusual urinary sensations. These symptoms can profoundly impact emotional and mental health, hinder participation in daily activities, disrupt social interactions, and strain personal relationships. Objective This study aimed to compare the experiences of different races and ethnicities with IC/BPS regarding symptoms, diagnosis, treatment status, and treatment methods. We hypothesized that there would be differences in racial and ethnic minority groups. Methods A cross-sectional web-based survey was administered between June and August 2022 through the Interstitial Cystitis Association and the Inspire web-based health community. Eligible adults resided in the United States, self-reported IC/BPS symptoms, and completed the survey in English. The instrument gathered demographic information, details regarding age at symptom onset, formal diagnosis status, and treatment use. Validated symptom and problem indices (the O’Leary-Sant Interstitial Cystitis Symptom Index and Problem Index) captured symptom severity and quality-of-life impact. Comparative analyses, including Fisher exact and median tests, were conducted across racial or ethnic groups (minority or multiple-race vs White and Hispanic vs non-Hispanic), and multivariable logistic regression assessed predictors of race or ethnicity on IC/BPS diagnosis status and treatment outcomes. Results In total, 1631 individuals completed the survey. Racial or ethnic minority or multiple-race respondents constituted 11.6% (n=189) of the sample. Although IC/BPS symptom severity (Interstitial Cystitis Symptom Index or Interstitial Cystitis Problem Index scores) did not significantly differ by race or ethnicity, minority or multiple-race respondents were 50% less likely to have a formal medical diagnosis of IC/BPS than White respondents (adjusted odds ratio 0.50, 95% CI 0.30‐0.83). Overall, 86.7% (n=1408) of participants reported having received a formal IC/BPS diagnosis, and the single strongest determinant of receiving any form of treatment was having a formal diagnosis (odds ratio 29.67, 95% CI 18.32‐48.05). Over 25% (n=385) of all respondents reported using narcotic or opioid medications, indicating the challenging nature of IC/BPS symptom management. Conclusions Minority or multiple-race participants were significantly less likely to have ever been diagnosed with IC/BPS by a health care professional, and those who were not diagnosed with IC/BPS were less likely to have used self-care behavioral and nonpharmacological treatments for their symptoms. Streamlining the diagnostic process and public health awareness campaigns outlining treatment options may help individuals manage IC/BPS symptoms.

PURPOSE:Congenital anomalies of the kidney and urinary tract (CAKUT) encompass heterogenous malformations arising from defective nephrogenesis. To date, approximately 50 monogenic genes are known to cause CAKUT if mutated. Recent studies show the impact of de novo variants in genetic disease etiology. Trio exome sequencing identifies de novo variants in novel candidate genes in 19.62% of CAKUT families. METHODS:We performed trio-based exome sequencing in 209 families with CAKUT to detect novel candidate disease genes. RESULTS:Trio analysis yielded in the identification of CAKUT candidate genes in 96 of 209 trio families (45.93%). In 41 of 209 cases, we detected strong de novo variants in 45 potential novel CAKUT candidate genes (19.62%). We developed a prioritization approach that highlights a truncating de novo variant in SOX13 (HGNC:11192) as a promising cause for CAKUT. In addition, further allele carriers for the candidate gene CHD1L (HGNC:1916) were identified, thus supporting the role of CHD1L in the pathogenesis of CAKUT. CONCLUSION:We conclude that de novo variants in potential novel CAKUT candidate genes contribute to the disease etiology and present SOX13 as a potential novel cause for CAKUT.

Background:Interstitial cystitis/bladder pain syndrome (IC/BPS) is a multifactorial, chronic syndrome involving urinary frequency, urgency, and bladder discomfort. These IC/BPS symptoms can significantly impact individuals' quality of life, affecting their mental, physical, sexual, and financial well-being. Individuals sometimes rely on peer-to-peer support to understand the disease and find methods of alleviating symptoms. The only US Food and Drug Administration-approved medication to treat IC/BPS is pentosan polysulfate sodium (PPS). However, ocular pigmentary maculopathy has been described in some individuals, with greater severity associated with prolonged PPS exposure. Objective:While prior research has separately assessed the benefits and side effects of PPS, this study sought to identify (1) sentiments of individuals with IC/BPS toward PPS and (2) topics discussed by individuals with IC/BPS in conjunction with PPS through use of an internet peer-to-peer forum. Methods:Data were collected from Inspire-an anonymous web-based health community where individuals gather by condition to find support and information. Sentiment analysis and percentages of negative, positive, and neutral sentiment for PPS discussions encompassing each topic was conducted using VADER (Valence Aware Dictionary for Sentiment Reasoning). Topic modeling was conducted using latent Dirichlet allocation. Words with the highest probability were ranked to categorize each topic, and authors manually investigated and labeled discussions. Results:There were 354 forum posts related to PPS. Topic modeling with latent Dirichlet allocation revealed 5 topic categories: "ineffectiveness or discontinued use," "alternative treatments," "personal treatment suggestions based on experience," "severe side effects," and "risk of long-term use." Topics related to "severe side effects" and "risk of long-term use" garnered less discussion, with the former also having the lowest positive sentiment (4.28, 14.29%). The topic "ineffectiveness or discontinued use" was most frequently discussed. This topic also had the highest percentage of negative posts (52/152, 34.21%). However, the average compound score was within the neutral compound score range (-0.094, SD 0.625). In addition, forum data highlighted individuals' acknowledgment of the efficacy of PPS in improving their quality of life, with statements such as "saved my sanity" being representative. The overall compound individuals' sentiment toward PPS was -0.083, split across 32.49% (115/354) negative, 22.03% (78/354) positive, and 45.48% (161/354) neutral sentiment categories. Conclusions:The overall authentic sentiment toward PPS is broad but balances to neutral. This neutral sentiment suggests that while some individuals express concerns about the side effects and long-term risks associated with PPS, others appreciate its positive impact on their quality of life. This research confirms that individuals with IC/BPS actively engage with health forums like Inspire to seek information, share their experiences, and explore different treatment options. As IC/BPS remains a complex syndrome, this study highlights the value of patient-led discussions in informing treatment decisions. Furthermore, these findings suggest that health care providers might benefit from considering the insights shared on peer-to-peer forums to better understand individual preferences, concerns, and expectations.

You have accessJournal of UrologyHistory of Urology Forum I (HF01)1 May 2024HF01-18 FORTUNE OF FORESIGHT: THE EVOLUTION OF PEDIATRIC UROLOGY AT BOSTON CHILDREN'S HOSPITAL (BCH) Jonathan T. Xu, Eric Bortnick, Carlos Estrada, and Stuart Bauer Jonathan T. XuJonathan T. Xu , Eric BortnickEric Bortnick , Carlos EstradaCarlos Estrada , and Stuart BauerStuart Bauer View All Author Informationhttps://doi.org/10.1097/01.JU.0001008828.35887.de.18AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: While BCH currently comprises the largest institutional cohort of pediatric urologists in the US, its beginnings as a nascent division were far from auspicious. In tracing the history of Urology at BCH from the late 1970s to it becoming a full-fledged Department, we aim to contextualize how events have historically defined and subsequently impacted the development of the field of pediatric urology. METHODS: An initial Google search was conducted to identify source material pertaining to the history of pediatric urology at BCH. Specific sources included a memoir authored by Alan Retik, oral history transcripts by W. Hardy Hendren, and oral interviews from Stuart Bauer. RESULTS: When Dr. Retik was appointed Chairman of the Division of Urology at BCH in 1977, pediatric urologic conditions were predominantly managed by pediatric surgeons and general urologists. Dr. Retik envisioned carving a niche for pediatric urologists to manage issues from incontinence in spina bifida to congenital genital anomalies. In those early days with Drs. Colodny and Bauer, Dr. Retik worked tirelessly to convince pediatricians of the necessity of providing specialized care for urologic disorders. When Dr. Hendren was appointed Chief of General Pediatric Surgery at BCH in 1982, Dr. Retik strived to maintain a cordial relationship with him without compromising his own aspirations and helped foster an environment where pediatric urologists and surgeons worked collaboratively to manage patients. Dr. Retik's passion for integrating physiologic studies of the lower urinary tract and basic research with interdisciplinary care led to the development of the first dedicated pediatric urodynamics laboratory headed by Dr. Bauer and appointed a pediatric radiologist, Dr. Robert Lebowitz, to join the division. Dr. Retik's penchant for mentorship also attracted recently graduated urologists with like-minded aspirations, culminating in the establishment of a pediatric urology fellowship in 1979. In 1996, the Division of Urology at BCH became a Department—a milestone which played an important role in cementing the legitimacy of pediatric urology as a separate specialty at BCH. CONCLUSIONS: Today, BCH Urology continues to impact the field with advancements in clinical care, research, and mentoring the next generation of pediatric urologists. Despite Dr. Retik's passing in 2022, his legacy lives on through the many lives he has touched – patients and providers – now and into the future. Source of Funding: None © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e285 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Jonathan T. Xu More articles by this author Eric Bortnick More articles by this author Carlos Estrada More articles by this author Stuart Bauer More articles by this author Expand All Advertisement PDF downloadLoading ...

Vesicoureteral reflux (VUR) is a medical condition where urine flows retrograde from the bladder superiorly, and has traditionally been considered a risk factor for kidney damage in children. However, over the past decade and a half, several randomized controlled trials have shown the risk of kidney damage in the presence of VUR is low, and any treatment for VUR does not change that risk. Here, we review the history of VUR as a pathologic condition, how the interpretation of that history led to possibly overestimating the danger, and how current findings should be seen in the context of that history.

Introduction Intra-detrusor botulinum toxin (Botox) injection is a minimally invasive alternative to augmentation cystoplasty in patients with refractory neurogenic bladder. Botox was first used for neurogenic bladder children two decades ago. However, there are no existing guidelines on indications or use among patients with spina bifida. Furthermore, there are little data regarding its use relative to bladder augmentation and patient volume on a national scale. Objective We sought to investigate the contemporary trends of intra-detrusor Botox injection and augment cystoplasty in free-standing children's hospitals. Study design We queried the Pediatric Health Information System database to identify spina bifida patients from 2016 to 2019 who underwent intra-detrusor Botox injection and augment cystoplasty based on CPT and ICD10 codes. Total spina bifida population under care in the free-standing children's hospitals was estimated by all inpatient and ambulatory surgery encounters as denominators to calculate frequency by time for both intra-detrusor Botox injections and augmentation cystoplasty. Results In total, we included 1924 intra-detrusor Botox injections and 842 augmentation cystoplasties. 1413 (51.1%) patients were female. Median age at surgery was 10.0 (interquartile range 6.98-13.5) years. There was a significant increase in intra-detrusor Botox injection frequency (p < 0.001). While there was an overall decreasing, but not significant, trend for augmentation cystoplasty, there was a significant increase in this procedure during the summer months compared to the rest of the year (p < 0.001, Figure 1). Sensitivity analysis using only first intradetrusor Botox injection per patient demonstrated similarly significant increasing trend. Discussion Use of intra-detrusor Botox injection for the management of neurogenic bladder has significantly increased among patients with spina bifida while augmentation cystoplasty has slightly decreased, but not significantly. Conclusions Over time, practice patterns for the treatments of neurogenic bladder among spina bifida children have favored minimally invasive Botox injections while augmentation cystoplasty use has not significantly changed.

PURPOSE:Urodynamic testing (UDS) is an important tool in the management of pediatric lower urinary tract conditions. There have been notable efforts to standardize pediatric UDS nomenclature and technique, but no formal guidelines exist on essential elements to include in a clinical report. We sought to identify ideal structure and elements of a pediatric UDS assessment based on expert consensus. MATERIALS AND METHODS:Pediatric urologists regularly performing UDS were queried using a Delphi process. Participants were invited representing varied geographic, experience, and societal involvement. Participants underwent 3 rounds of questionnaires between November 2022 and August 2023 focusing on report organization, elements, definitions, and automated electronic health record clinical decision support. Professional billing requirements were also considered. Consensus was defined as 80% agreeing either in favor of or against a topic. Elements without consensus were discussed in subsequent rounds. RESULTS:A diverse sample of 30 providers, representing 27 institutions across 21 US states; Washington, District of Columbia; and Canada completed the study. Participants reported interpreting an average number of 5 UDS reports per week (range 1-22). The finalized consensus report identifies 93 elements that should be included in a pediatric UDS report based on applicable study conditions and findings. CONCLUSIONS:This consensus report details the key elements and structure agreed upon by an expert panel of pediatric urologists. Further standardization of documentation should aid collaboration and research for patients undergoing UDS. Based on this information, development of a standardized UDS report template using electronic health record implementation principles is underway, which will be openly available for pediatric urologists.

INTRODUCTION:Clean intermittent catheterization (CIC) is a well-established method of managing lower urinary tract dysfunction. Depending on the age at introduction, caregivers might perform CIC initially but then transition responsibility to their children. Little is known about how to support families during this transition. Our aim is to learn the facilitators and challenges experienced when supporting the transition from caregiver-led CIC to patient self-CIC.MATERIALS AND METHODS:A phenomenological approach was used to gather information from caregivers and children >12 years through semistructured interviews. Thematic analysis was utilized to generate themes around experience with the transition from caregiver-led CIC to patient self-CIC.RESULTS:Of the 40 families interviewed, 25 families underwent successful transition to patient self-CIC. Analysis of excerpts identified a three-step process, including (1) desiring to learn self-CIC, (2) practical learning of CIC techniques, and (3) mastering of techniques leading to emotional and physical independence. Many families experienced challenges in transitioning to self-CIC, including patient or caregiver reluctance, improper equipment, past negative experiences, lack of knowledge about urinary tract anatomy and function, abnormal anatomy, and/or moderate to severe intellectual disability.DISCUSSION:Authors reviewed interventions to address challenges and provide clinical care recommendations to enhance success during the transition to patient self-CIC.CONCLUSION:No prior studies have identified this stepwise process that occurs in the transition from caregiver-led CIC to patient self-CIC. Healthcare providers and school officials (where indicated) can support families during this transition, with attention to facilitators and challenges identified in this study.

This chapter provides a thorough explanation on how to approach a child who presents with lower urinary tract dysfunction, whether it be of neurogenic, anatomic, or functional origin. Formation of a urodynamic question after a comprehensive history and physical examination is paramount in selecting the urodynamic study(ies) that will be most appropriate for each child. Considerate application of each test in a stepwise manner, while including the parent and child throughout the process, will provide the most accurate and reproducible results. Recommendations on how to execute each of the components of a urodynamic study, as well as interpretation, are included in this chapter.

INTRODUCTION:Clean intermittent catheterization (CIC) is often used for bladder emptying in children with lower urinary tract dysfunction. Until recently, the emphasis in assessing the effects of CIC has been on preserving kidney function, reducing urinary tract infection, and achieving urinary continence. Few studies have investigated the impact of CIC on students and families in a school setting. This study sought to examine what students and caregivers experienced when CIC was required during the school day and how schools adjusted to a student needing to perform it. MATERIALS AND METHODS:A phenomenological approach utilizing semistructured interviews was performed to understand the impact of CIC on students. Purposeful sampling identified eligible families. A guide was developed from expert opinion validated by a pilot sample with feedback collated into a family/provider codesigned questionnaire. Interviews emphasized the impact and challenges students faced at school. Transcripts were coded using Dedoose software with emerging themes identified and a code book was created for closed coding that led to thematic analysis. RESULTS:A total of 40 families (52 caregivers and children > 12 years) were interviewed. Emergent themes included: Caregivers and students felt (1) school personnel were not always aware of nor prepared regarding the implications of CIC; (2) school bathrooms were often less than ideal (e.g., location, size, cleanliness, privacy, and availability); and (3) student participation in extracurricular activities was challenging. CONCLUSIONS:This study identifies potential areas of intervention in meeting the needs of students who require CIC and the importance of having collaborative efforts of caregivers, health care providers, and school personnel in addressing and meeting CIC needs. Care coordination that involves consistent communication and careful planning between health care teams, school personnel, students, and caregivers can optimize a student's educational experience.

Background:There is limited quality of evidence regarding the accuracy of contrast-enhanced voiding urosonography (ceVUS) for diagnosis of vesicoureteral reflux (VUR) compared to fluoroscopic voiding cystourethrography (VCUG), and minimal data on the use of the ultrasound contrast agent Optison (TM) for this purpose. Objective:To compare the accuracy of ceVUS using Optison (TM) to VCUG, and to assess inter-rater agreement regarding presence and grading of VUR. Study designIn this retrospective investigation, all sequential ceVUS with OptisonTM and VCUG studies performed in children between 2014 and 2017 were reviewed. Two raters independently graded all ceVUS studies using a 5-point scale. CeVUS sensitivity and specificity were estimated separately for each rater using the VCUG report as the ground truth for presence and degree of VUR. Logistic and ordinary linear regression models assessed rater-report agreement and inter-rater agreement for each kidney, Optison (TM) dose, and referral diagnosis. Results:97 children (51 females) with 101 paired studies were included. Sensitivity and specificity of ceVUS for VUR detection were identical for both raters: right kidney 75%/90.9%; left kidney 85.7%/78.9% (Figure). There was no statistically significant difference in disagreement between raters and the VCUG report for the right or left kidney. Inter-rater agreement on ceVUS grading was 90% and 88% for right and left kidneys, respectively. There was a significant negative association between fetal hydronephrosis vs urinary tract infection and disagreement between Rater 2 and the VCUG report for the left kidney. There were no other significant associations with respect to either kidney, Optison (TM) dose, or referral diagnosis. Discussion:Our study showed that detection of VUR with ceVUS and Optison (TM) is comparable to fluoroscopic VCUG. Based on the VCUG reports, the incidence of VUR in our patient population was substantially lower than in the meta-analysis of Chua et al. and in the study of Kim et al. The explanation for the large discrepancy in VUR incidence may reflect differences in the patient populations, and in our reporting of VUR with respect to kidney number rather than to pelviureteral units. Study limitations include its retrospective nature and potential bias in terms of patient selection. Since VUR is an intermittent phenomenon, sequential rather than simultaneous performance of the ceVUS and fluoroscopic studies might have influenced VUR detection. Conclusion:A blinded comparison of ceVUS performed with Optison (TM) to fluoroscopic VCUG showed moderate-good sensitivity and specificity for diagnosis of VUR.

You have accessJournal of UrologyCME1 Apr 2023MP60-02 ATP2C1 IS A CANDIDATE FOR INTERSTITIAL CYSTITIS/BLADDER PAIN SYNDROME Catherine Brownstein, Elicia Estrella, Shira Rockowitz, Marielle Thorne, Pressley Smith, Jeanette Petit, Veronica Zehnder, Richard Yu, Stuart Bauer, Charles Berde, Pankaj Agrawal, Alan Beggs, Louis Kunkel, and Ali Gharavi Catherine BrownsteinCatherine Brownstein More articles by this author , Elicia EstrellaElicia Estrella More articles by this author , Shira RockowitzShira Rockowitz More articles by this author , Marielle ThorneMarielle Thorne More articles by this author , Pressley SmithPressley Smith More articles by this author , Jeanette PetitJeanette Petit More articles by this author , Veronica ZehnderVeronica Zehnder More articles by this author , Richard YuRichard Yu More articles by this author , Stuart BauerStuart Bauer More articles by this author , Charles BerdeCharles Berde More articles by this author , Pankaj AgrawalPankaj Agrawal More articles by this author , Alan BeggsAlan Beggs More articles by this author , Louis KunkelLouis Kunkel More articles by this author , and Ali GharaviAli Gharavi More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003318.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) is a chronic pain disorder causing symptoms of urinary frequency, urgency and bladder discomfort. METHODS: We performed genetic analyses of whole exome sequencing (ES) on a total of 109 individuals with IC/BPS (93 female and 16 male). Each individual had a cystoscopy, physical exam, urinalysis, and completed questionnaires including the O’Leary- Sant for women, and the NIH-CPSI for men. Our study urologist confirmed the IC/BPS diagnosis. Data was analyzed in Codified Genomics for Mendelian variants. SKAT analysis was performed in Genuity Science for a small list of candidate genes, based on the results of the Mendelian analysis. RESULTS: One family had a previously reported SIX5 variant (ENST00000317578.6:c.472G>A, p.Ala158Thr), consistent with Branchiootorenal syndrome 2 (BOR2). A likely pathogenic heterozygous variant in ATP2A2 (ENST00000539276.2:c.235G>A, p.Glu79Lys) was identified in two probands, indicating possible Darier-White disease. Two private heterozygous variants were identified in ATP2C1 (ENST00000393221.4:c.2358A>T, p.Glu786Asp (VUS/Likely Pathogenic) and ENST00000393221.4:c.989C>G, p.Thr330Ser (Likely Pathogenic)), indicative of Hailey-Hailey Disease. SKAT analysis found a trend towards increased burden of rare ATP2C1 variants in the IC/BPS cases vs a control cohort (p=0.03, OR=6.76), though did not survive Bonferroni correction. CONCLUSIONS: Our data suggest that some individuals with IC/BPS may have unrecognized Mendelian syndromes, and ATP2C1, ATP2A2, and SIX5 may be candidate genes for IC/BPS.Impairment of ATP2C1 leads to a dysfunction in the Golgi-associated human secretory pathway Ca2+/Mn2+ ATPase (hSPCA1) that results in recurrent blisters and erosions in intertriginous sites. Studies show that knockdown of SPCA1 results in disruption of Golgi morphology in HeLa cells, and reduction of the amount of Ca2+ stored in the Golgi lumen. The Golgi complex is tightly integrated into the urothelial cellular system, where it is crucial for the health of the blood–urine barrier, mainly through its association with uroplakins. One can hypothesize that mutations of ATP2C1 may also result in a disruption of Golgi morphology in urothelial tissue, impairing the formation of the blood-urine barrier, a hallmark of IC/BPS. Genetically screening individuals with IC/BPS may be useful in diagnosing and treating this painful disorder due to its heterogeneous nature. Source of Funding: This work was funded by NIH 5U54DK104309-07, CDC 1U01DP006634-01-00, P50HD105351, and the Broad Institute BCH Collaborative Grant Award. © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e842 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Catherine Brownstein More articles by this author Elicia Estrella More articles by this author Shira Rockowitz More articles by this author Marielle Thorne More articles by this author Pressley Smith More articles by this author Jeanette Petit More articles by this author Veronica Zehnder More articles by this author Richard Yu More articles by this author Stuart Bauer More articles by this author Charles Berde More articles by this author Pankaj Agrawal More articles by this author Alan Beggs More articles by this author Louis Kunkel More articles by this author Ali Gharavi More articles by this author Expand All Advertisement PDF downloadLoading ...

BACKGROUND:Congenital anomalies of the kidneys and urinary tract (CAKUT) constitute the most common cause of chronic kidney disease in the first three decades of life. Variants in four Forkhead box (FOX) transcription factors have been associated with CAKUT. We hypothesized that other FOX genes, if highly expressed in developing kidneys, may also represent monogenic causes of CAKUT. METHODS:We here performed whole-exome sequencing (WES) in 541 families with CAKUT and generated four lists of CAKUT candidate genes: (A) 36 FOX genes showing high expression during renal development, (B) 4 FOX genes known to cause CAKUT to validate list A, (C) 80 genes that we identified as unique potential novel CAKUT candidate genes when performing WES in 541 CAKUT families and (D) 175 genes identified from WES as multiple potential novel CAKUT candidate genes. RESULTS:To prioritize potential novel CAKUT candidates in the FOX gene family, we overlapped 36 FOX genes (list A) with lists C and D of WES-derived CAKUT candidates. Intersection with list C identified a de novo FOXL2 in-frame deletion in a patient with eyelid abnormalities and ureteropelvic junction obstruction, and a homozygous FOXA2 missense variant in a patient with horseshoe kidney. Intersection with list D identified a heterozygous FOXA3 missense variant in a CAKUT family with multiple affected individuals. CONCLUSIONS:We hereby identified FOXL2, FOXA2 and FOXA3 as novel monogenic candidate genes of CAKUT, supporting the utility of a paralog-based approach to discover mutated genes associated with human disease.

You have accessJournal of UrologyCME1 May 2022PD02-01 PRENATAL CLOSURE OF MYELOMENINGOCELE IS ASSOCIATED WITH HIGHER RISK FOR EARLY SECONDARY SPINAL CORD TETHERING Hsin-Hsiao Wang, Duncan Morhardt, Benjamin Warf, Lawrence Karlin, Asal Hojjat, Shahram Khoshbin, Erin Mcnamara, Carlos Estrada, and Stuart Bauer Hsin-Hsiao WangHsin-Hsiao Wang More articles by this author , Duncan MorhardtDuncan Morhardt More articles by this author , Benjamin WarfBenjamin Warf More articles by this author , Lawrence KarlinLawrence Karlin More articles by this author , Asal HojjatAsal Hojjat More articles by this author , Shahram KhoshbinShahram Khoshbin More articles by this author , Erin McnamaraErin Mcnamara More articles by this author , Carlos EstradaCarlos Estrada More articles by this author , and Stuart BauerStuart Bauer More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002517.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The long-term impact of prenatal myelomeningocele (MMC) closure on neuro-urologic function is unclear. Urodynamic studies (UDS) often serve as an early indicator of symptomatically acquired spinal cord tethering. We sought to compare the risk for early neuro-urologic deterioration due to spinal cord tethering in children with prenatal versus postnatal MMC repair. METHODS: Children with prenatal MMC closure followed at our institution from 1999 to 2019 were included. Children with postnatally closed MMC were selected as matched controls in 1:3 ratio by sex, neurological level, & follow-up. Primary outcome was defined as time to secondary untethering procedure. Birth year, gender, functional neurological level, UDS & reasons for surgery were assessed. Multivariate cox proportional hazard model was fitted. RESULTS: Our study included 21 with prenatal & 62 with postnatal MMC closure. 12/21 (57%) of the prenatally and 15/62 (24%) of the postnatally closed babies underwent secondary spinal cord surgery (SSCS). Median age for SSCS in those closed prenatal was younger (median 16 [IQR 13-62] months) compared to the postnatal group (median 69 [IQR 35-120] months, p=0.02). Compared to the postnatal MMC group, prenatal MMC closure was significantly associated with need for SSCS (p <0.01, figure 1). When adjusting for birth year, sex, functional neurologic level, prenatal MMC closure remained significantly associated with the need for untethering surgery (HR=4.7(2.5-12.0), p <0.001). Under the same MMC bladder management protocol for both groups, 8/12 (67%) of prenatally closed children requiring secondary untethering surgery had symptomatic UDS changes, with 7/8 (88%) showing improved postoperative UDS parameters. Similarly, 93% (14/15) of postnatally closed children with acquired tethering had UDS changes, with 11/14 (78%) showing improved postoperative UDS. CONCLUSIONS: We found substantially more children with prenatal MMC closure who required SSCS compared to those closed postnatally. In each group, most presented with worsening UDS parameters. Early detection of UDS changes & secondary untethering resulted in neuro-urologic improvement. The cause of this phenomenon is not clear and requires further investigation. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e35 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hsin-Hsiao Wang More articles by this author Duncan Morhardt More articles by this author Benjamin Warf More articles by this author Lawrence Karlin More articles by this author Asal Hojjat More articles by this author Shahram Khoshbin More articles by this author Erin Mcnamara More articles by this author Carlos Estrada More articles by this author Stuart Bauer More articles by this author Expand All Advertisement PDF DownloadLoading ...