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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.
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Consenso , Técnica Delphi , Urodinámica , Humanos , Niño , Urología/normas , Pediatría/normas , Masculino , Encuestas y CuestionariosRESUMEN
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.
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Cateterismo Uretral Intermitente , Infecciones Urinarias , Niño , Humanos , Vejiga Urinaria , Encuestas y Cuestionarios , Estudiantes , Cateterismo UrinarioRESUMEN
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.
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Cateterismo Uretral Intermitente , Vejiga Urinaria Neurogénica , Sistema Urinario , Niño , Humanos , Cuidadores , Cateterismo Uretral Intermitente/métodos , Vejiga Urinaria , Vejiga Urinaria Neurogénica/terapiaRESUMEN
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™ for this purpose. OBJECTIVE: To compare the accuracy of ceVUS using Optison™ to VCUG, and to assess inter-rater agreement regarding presence and grading of VUR. STUDY DESIGN: In this retrospective investigation, all sequential ceVUS with Optison™ 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™ 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™ dose, or referral diagnosis. DISCUSSION: Our study showed that detection of VUR with ceVUS and Optison™ 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™ to fluoroscopic VCUG showed moderate-good sensitivity and specificity for diagnosis of VUR.
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Reflujo Vesicoureteral , Niño , Femenino , Humanos , Medios de Contraste , Cistografía/métodos , Riñón/diagnóstico por imagen , Estudios Retrospectivos , Ultrasonografía/métodos , Micción , Reflujo Vesicoureteral/diagnóstico por imagen , MasculinoRESUMEN
INTRODUCTION: Since its inception >50 years ago, clean intermittent catheterization (CIC) has become ubiquitous in managing lower urinary tract dysfunction in children. Emphasis has been on its impact on daily life, but little on its implementation and adjustment in families. The aim of the current study was to discover how families learned to implement and manage their child's CIC needs by interviewing caregivers, adolescents, and young adults about their experiences. Interviews were designed to uncover facilitators and barriers to beginning CIC to initiate potential improvements in a multidisciplinary approach. METHODS: A semi-structured interview guide was developed and piloted initially to 12 families for validation. Between August 2018 and October 2019, 40 families (52 interviews of caregivers and patients >12 years) were then interviewed with open-ended questions interspersed with more specific ones to generate discussion. Transcripts were coded using Dedoose software to create a base list with emergent codes. Inductive and deductive methods were employed to generate themes. Consensus was reached during successive team meetings. RESULTS: Five major and several subthemes emerged regarding implementation of CIC by caregivers and patients learning CIC for the first time. THEME 1: Parental reaction to CIC: Caregivers described benefits of an adjustment period on learning their child's need for CIC. Prenatal information to caregivers of spina bifida children gave them time to mentally process the need for CIC. THEME 2: Ease of learning CIC: impact of age and gender: caregivers identified advantages of initiating CIC in infancy. Caregivers speculated CIC was physically easier in boys than girls due to meatus location. Developmentally ready children expressed a desire for independence and privacy as they learned to initiate CIC. THEME 3: The impact of additional caregiver support in learning and performing CIC: presence of multiple caregivers optimized learning and implementation of CIC. Having secondary caregivers available provided peace of mind and more flexibility in maintaining reliable CIC care. Patients learning CIC found it helpful to have a parent present at the teaching session. Occasionally, female caregivers reported feelings of anger and frustration when male caregivers were reluctant to be involved in catheterization, irrespective of their child's gender. THEME 4: Satisfaction with healthcare team's approach: The healthcare team's responsiveness to their learning needs affected how they mastered CIC. The healthcare team's teaching and reassurance helped build caregiver confidence. Developmentally appropriate children were able to learn self-catheterization when supported by the healthcare team. Patients learning self-CIC articulated having a supportive healthcare team was helpful with implementation. THEME 5: Effect of CIC on employment status relative to job changes, insurance, and daycare: implementing and performing CIC presented a spectrum of issues related to employment. Educating employers regarding CIC facilitated a caregiver's ability to both remain at work and administer to their child. Caregivers underscored the importance of adequate insurance when considering employment choices. Concerns about daycare availability affected caregivers' work schedules. CONCLUSIONS: It is anticipated this information will aid healthcare personnel to more effectively teach and initiate CIC in families, and in individuals learning for the first time. The findings should serve as the basis for conducting future patient satisfaction studies, which would determine the effectiveness and reproducibility of these approaches.
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Cateterismo Uretral Intermitente , Niño , Adolescente , Adulto Joven , Humanos , Masculino , Femenino , Cateterismo Uretral Intermitente/métodos , Reproducibilidad de los Resultados , Padres , Satisfacción del Paciente , CuidadoresRESUMEN
Background: Congenital anomalies of the kidneys and urinary tract (CAKUT) are the most common cause of chronic kidney disease among children and adults younger than 30 yr. In our previous study, whole-exome sequencing (WES) identified a known monogenic cause of isolated or syndromic CAKUT in 13% of families with CAKUT. However, WES has limitations and detection of copy number variations (CNV) is technically challenging, and CNVs causative of CAKUT have previously been detected in up to 16% of cases. Objective: To detect CNVs causing CAKUT in this WES cohort and increase the diagnostic yield. Design setting and participants: We performed a genome-wide single nucleotide polymorphism (SNP)-based CNV analysis on the same CAKUT cohort for whom WES was previously conducted. Outcome measurements and statistical analysis: We evaluated and classified the CNVs using previously published predefined criteria. Results and limitations: In a cohort of 170 CAKUT families, we detected a pathogenic CNV known to cause CAKUT in nine families (5.29%, 9/170). There were no competing variants on genome-wide CNV analysis or WES analysis. In addition, we identified novel likely pathogenic CNVs that may cause a CAKUT phenotype in three of the 170 families (1.76%). Conclusions: CNV analysis in this cohort of 170 CAKUT families previously examined via WES increased the rate of diagnosis of genetic causes of CAKUT from 13% on WES to 18% on WES + CNV analysis combined. We also identified three candidate loci that may potentially cause CAKUT. Patient summary: We conducted a genetics study on families with congenital anomalies of the kidney and urinary tract (CAKUT). We identified gene mutations that can explain CAKUT symptoms in 5.29% of the families, which increased the percentage of genetic causes of CAKUT to 18% from a previous study, so roughly one in five of our patients with CAKUT had a genetic cause. These analyses can help patients with CAKUT and their families in identifying a possible genetic cause.
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PURPOSE: Congenital anomalies of the kidneys and urinary tract (CAKUT) constitute the leading cause of chronic kidney disease in children. In total, 174 monogenic causes of isolated or syndromic CAKUT are known. However, syndromic features may be overlooked when the initial clinical diagnosis of CAKUT is made. We hypothesized that the yield of a molecular genetic diagnosis by exome sequencing (ES) can be increased by applying reverse phenotyping, by re-examining the case for signs/symptoms of the suspected clinical syndrome that results from the genetic variant detected by ES. METHODS: We conducted ES in an international cohort of 731 unrelated families with CAKUT. We evaluated ES data for variants in 174 genes, in which variants are known to cause isolated or syndromic CAKUT. In cases in which ES suggested a previously unreported syndromic phenotype, we conducted reverse phenotyping. RESULTS: In 83 of 731 (11.4%) families, we detected a likely CAKUT-causing genetic variant consistent with an isolated or syndromic CAKUT phenotype. In 19 of these 83 families (22.9%), reverse phenotyping yielded syndromic clinical findings, thereby strengthening the genotype-phenotype correlation. CONCLUSION: We conclude that employing reverse phenotyping in the evaluation of syndromic CAKUT genes by ES provides an important tool to facilitate molecular genetic diagnostics in CAKUT.
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Sistema Urinario , Anomalías Urogenitales , Alelos , Exoma/genética , Humanos , Riñón/anomalías , Anomalías Urogenitales/genética , Reflujo VesicoureteralRESUMEN
Congenital anomalies of the kidneys and urinary tract (CAKUT) constitute the most common cause of early-onset chronic kidney disease. In a previous study, we identified a heterozygous truncating variant in nuclear receptor-interacting protein 1 (NRIP1) as CAKUT causing via dysregulation of retinoic acid signaling. This large family remains the only family with NRIP1 variant reported so far. Here, we describe one additional CAKUT family with a truncating variant in NRIP1. By whole-exome sequencing, we identified one heterozygous frameshift variant (p.Asn676Lysfs*27) in an isolated CAKUT patient with bilateral hydroureteronephrosis and right grade V vesicoureteral reflux (VUR) and in the affected father with left renal hypoplasia. The variant is present twice in a heterozygous state in the gnomAD database of 125,000 control individuals. We report the second CAKUT family with a truncating variant in NRIP1, confirming that loss-of-function mutations in NRIP1 are a novel monogenic cause of human autosomal dominant CAKUT.
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Sistema Urinario , Anomalías Urogenitales , Reflujo Vesicoureteral , Árabes , Humanos , Riñón/anomalías , Proteína de Interacción con Receptores Nucleares 1/genética , Anomalías Urogenitales/diagnóstico , Anomalías Urogenitales/genética , Reflujo Vesicoureteral/genética , Secuenciación del ExomaRESUMEN
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.
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Sistema Urinario , Anomalías Urogenitales , Proteína Forkhead Box L2/genética , Factor Nuclear 3-beta del Hepatocito/genética , Factor Nuclear 3-gamma del Hepatocito/genética , Humanos , Riñón/anomalías , Sistema Urinario/anomalías , Anomalías Urogenitales/genética , Reflujo Vesicoureteral , Secuenciación del ExomaRESUMEN
AIMS: We aimed to describe the effectiveness of Onabotulinumtoxin A (Botox) in children with neurogenic bladder (NGB) unresponsive to medical therapy to determine urodynamic parameters predictive of success. METHODS: Children receiving Botox for refractory NGB, between 2008 and 2019, from a single academic center, were included in this study. Botox success was defined as improvement of incontinence and/or urodynamic parameters. RESULTS: Of 34 patients who received Botox, 13 (38.2%) had a positive response from their first injection, with improvement in capacity by a median of 35% of expected capacity for age compared to only a 9% increase in those who did not respond clinically. When patients were divided into groups by baseline urodynamic parameters, high-pressure (Pdetmax > 20 cm H2 O) patients had significantly greater improvement in compliance compared with low-pressure patients (p = 0.017). Low compliance patients (<10 ml/cm H2 O) had a dramatic improvement of 3.08 ml/cm H2 O in their compliance compared with minimal change in the high compliance group (p = 0.003). Finally, low-capacity (<50% of expected CC) patients had significant improvement in capacity and compliance when compared with high-capacity patients (p = 0.004 and p = 0.036, respectively). Improvement in detrusor overactivity (DO) was noted in both the clinical responders and non-responders. CONCLUSION: In our series, 38% had clinical success with intradetrusor Botox injections for refractory neurogenic bladder. When successful, improvement in capacity and compliance, DO, and/or incontinence was consistent with prior literature. While we could not determine which parameters predicted success, subdividing patients into categories based on baseline urodynamic parameters identified who would benefit from Botox treatment based on differential improvements in capacity and compliance. At least 1 injection of Botox should be considered for a subset of children with refractory NGB, before undertaking more invasive treatments.
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Toxinas Botulínicas Tipo A , Fármacos Neuromusculares , Vejiga Urinaria Neurogénica , Vejiga Urinaria Hiperactiva , Toxinas Botulínicas Tipo A/uso terapéutico , Niño , Humanos , Fármacos Neuromusculares/uso terapéutico , Vejiga Urinaria Neurogénica/tratamiento farmacológico , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , UrodinámicaRESUMEN
AIMS: To investigate the effect of losartan on preventing bladder fibrosis and protecting renal function in rats with neurogenic paralysis bladder (NPB). MATERIALS AND METHODS: Rats were assigned to the transecting spinal nerves group (TSNG), transecting spinal nerves + losartan group (LSTG), and control group (CG). On Day 32 postsurgery, bladder capacity (BC), bladder compliance (ΔC), bladder leakage pressure (Pves.leak ) of TSNG and LSTG while BC, ΔC, and bladder threshold pressure (Pves.thre ) of CG were measured by cystometry in each cohort. Renal function and the expression quantity of Angiotensin â ¡ (Ang II) in blood were detected, in addition Ang II, Ang II Type 1 receptor (AT1), transformation growth factor ß1 (TGFß1), Collagen â ¢, and collagen fibrin in the bladder tissue were detected too. RESULTS: ΔC in TSNG and LSTG decreased significantly compared to the CG. Pves.leak in TSNG and LSTG were significantly higher than Pves.thre in CG. Renal function of both TSNG and LSTG decreased significantly compared with the CG, but renal function in LSTG was better than in TSNG. Ang â ¡ in blood and bladder tissue in TSNG and LSTG increased significantly compared with CG. AT1 was expressed in the bladder tissue of all rats. The TGFß1, Collagen â ¢, and collagen fibrin expression level increased significantly in TSNG compared with LSTG and CG, while these levels were not significantly different between CG and LSTG. CONCLUSION: Losartan might prevent NPB fibrosis by stopping the upregulated signaling of Ang II/AT1/TGFß1 and consequently may reduce kidney damage from occurring.
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Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Fibrosis/tratamiento farmacológico , Losartán/uso terapéutico , Vejiga Urinaria Neurogénica/tratamiento farmacológico , Vejiga Urinaria/efectos de los fármacos , Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacología , Animales , Modelos Animales de Enfermedad , Losartán/farmacología , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
Congenital anomalies of the kidney and urinary tract (CAKUT) constitute one of the most frequent birth defects and represent the most common cause of chronic kidney disease in the first three decades of life. Despite the discovery of dozens of monogenic causes of CAKUT, most pathogenic pathways remain elusive. We performed whole-exome sequencing (WES) in 551 individuals with CAKUT and identified a heterozygous de novo stop-gain variant in ZMYM2 in two different families with CAKUT. Through collaboration, we identified in total 14 different heterozygous loss-of-function mutations in ZMYM2 in 15 unrelated families. Most mutations occurred de novo, indicating possible interference with reproductive function. Human disease features are replicated in X. tropicalis larvae with morpholino knockdowns, in which expression of truncated ZMYM2 proteins, based on individual mutations, failed to rescue renal and craniofacial defects. Moreover, heterozygous Zmym2-deficient mice recapitulated features of CAKUT with high penetrance. The ZMYM2 protein is a component of a transcriptional corepressor complex recently linked to the silencing of developmentally regulated endogenous retrovirus elements. Using protein-protein interaction assays, we show that ZMYM2 interacts with additional epigenetic silencing complexes, as well as confirming that it binds to FOXP1, a transcription factor that has also been linked to CAKUT. In summary, our findings establish that loss-of-function mutations of ZMYM2, and potentially that of other proteins in its interactome, as causes of human CAKUT, offering new routes for studying the pathogenesis of the disorder.
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Proteínas de Unión al ADN/genética , Epigénesis Genética , Factores de Transcripción Forkhead/genética , Mutación , Proteínas Represoras/genética , Factores de Transcripción/genética , Sistema Urinario/metabolismo , Anomalías Urogenitales/genética , Proteínas Anfibias/antagonistas & inhibidores , Proteínas Anfibias/genética , Proteínas Anfibias/metabolismo , Animales , Estudios de Casos y Controles , Niño , Preescolar , Proteínas de Unión al ADN/metabolismo , Familia , Femenino , Factores de Transcripción Forkhead/metabolismo , Heterocigoto , Humanos , Lactante , Larva/genética , Larva/crecimiento & desarrollo , Larva/metabolismo , Masculino , Ratones , Ratones Noqueados , Morfolinos/genética , Morfolinos/metabolismo , Linaje , Unión Proteica , Proteínas Represoras/metabolismo , Factores de Transcripción/metabolismo , Sistema Urinario/anomalías , Anomalías Urogenitales/metabolismo , Anomalías Urogenitales/patología , Secuenciación del Exoma , XenopusRESUMEN
PURPOSE: Congenital anomalies of the kidney and urinary tract (CAKUT) are the most common cause of chronic kidney disease in childhood and adolescence. We aim to identify novel monogenic causes of CAKUT. METHODS: Exome sequencing was performed in 550 CAKUT-affected families. RESULTS: We discovered seven FOXC1 heterozygous likely pathogenic variants within eight CAKUT families. These variants are either never reported, or present in <5 alleles in the gnomAD database with ~141,456 controls. FOXC1 is a causal gene for Axenfeld-Rieger syndrome type 3 and anterior segment dysgenesis 3. Pathogenic variants in FOXC1 have not been detected in patients with CAKUT yet. Interestingly, mouse models for Foxc1 show severe CAKUT phenotypes with incomplete penetrance and variable expressivity. The FOXC1 variants are enriched in the CAKUT cohort compared with the control. Genotype-phenotype correlations showed that Axenfeld-Rieger syndrome or anterior segment dysgenesis can be caused by both truncating and missense pathogenic variants, and the missense variants are located at the forkhead domain. In contrast, for CAKUT, there is no truncating pathogenic variant, and all variants except one are located outside the forkhead domain. CONCLUSION: We thereby expanded the phenotype of FOXC1 pathogenic variants toward involvement of CAKUT, which can potentially be explained by allelism.
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Anomalías del Ojo , Sistema Urinario , Niño , Factores de Transcripción Forkhead/genética , Heterocigoto , Humanos , Riñón , FenotipoRESUMEN
AIMS: No one has assessed urodynamic studies (UDS) to determine those steps that elicit the greatest anxiety, distress, and pain in children. We sought to systematically evaluate a child's UDS experience to mollify these reactions. METHODS: Prospective study involving children aged ≥5 undergoing UDS over a 6-month period (from 10 December 2018 to 22 May 2019). Upon arrival, patients completed a visual analog scale for anxiety (VAS-A, 0-10) about the upcoming procedure. A research assistant assessed the patient's behavior during each major step of UDS using a validated brief behavioral distress scale. Nursing staff also obtained patients' pain ratings (0-10) for these key elements. Immediately after UDS, each child completed a posttest VAS-A along with a survey about the UDS experience. RESULTS: A total of 76 UDS were observed; almost half included sphincter needle electromyography (EMG). Mean patient VAS-A scores were 2.3 before UDS, compared to 0.8 afterward (P < .001). The highest proportion of distressful behaviors were observed during EMG needle (31%) and urethral catheter (29%) insertion, in agreement with the highest mean pain scores of 3.2 and 2.7, respectively. Fifty-four percent of children reported not being completely aware of what was going to happen before the procedure and 50% of those patients exhibited at least one interfering or potentially interfering behavior. Similarly, 60% of children with no prior history of UDS exhibited at least one interfering or potentially interfering behavior. CONCLUSIONS: EMG needle and urethral catheter placement, initial urodynamic testing and not knowing what to expect were associated with greater pain and distress during pediatric UDS.
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Ansiedad/fisiopatología , Dolor/fisiopatología , Uretra/fisiopatología , Urodinámica/fisiología , Adolescente , Adulto , Ansiedad/psicología , Niño , Preescolar , Electromiografía , Femenino , Humanos , Masculino , Dolor/psicología , Estudios Prospectivos , Encuestas y Cuestionarios , Escala Visual Analógica , Adulto JovenRESUMEN
Congenital anomalies of the kidney and urinary tract (CAKUT) are the most common cause of chronic kidney disease in the first three decades of life, and in utero obstruction to urine flow is a frequent cause of secondary upper urinary tract malformations. Here, using whole-exome sequencing, we identified three different biallelic mutations in CHRNA3, which encodes the α3 subunit of the nicotinic acetylcholine receptor, in five affected individuals from three unrelated families with functional lower urinary tract obstruction and secondary CAKUT. Four individuals from two families have additional dysautonomic features, including impaired pupillary light reflexes. Functional studies in vitro demonstrated that the mutant nicotinic acetylcholine receptors were unable to generate current following stimulation with acetylcholine. Moreover, the truncating mutations p.Thr337Asnfs∗81 and p.Ser340∗ led to impaired plasma membrane localization of CHRNA3. Although the importance of acetylcholine signaling in normal bladder function has been recognized, we demonstrate for the first time that mutations in CHRNA3 can cause bladder dysfunction, urinary tract malformations, and dysautonomia. These data point to a pathophysiologic sequence by which monogenic mutations in genes that regulate bladder innervation may secondarily cause CAKUT.
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Enfermedades del Sistema Nervioso Autónomo/etiología , Riñón/anomalías , Mutación , Receptores Nicotínicos/genética , Sistema Urinario/anomalías , Anomalías Urogenitales/etiología , Adulto , Enfermedades del Sistema Nervioso Autónomo/genética , Enfermedades del Sistema Nervioso Autónomo/patología , Femenino , Estudios de Seguimiento , Humanos , Riñón/patología , Masculino , Linaje , Pronóstico , Sistema Urinario/patología , Anomalías Urogenitales/genética , Anomalías Urogenitales/patología , Adulto JovenRESUMEN
AIMS: To introduce the standard procedure of cystometry and interpretation of the results in children. METHODS: The literature on cystometry in children in PubMed for the last 20 years was reviewed. The updated knowledge regarding indication, preparation, technique, and interpretation of cystometry in children were summarized. RESULTS: Filling cystometry is the core content of a paediatric urodynamic study. In this section, the technique for performing cystometry is introduced in details. Emphasis is placed on correctly setting up the equipment according to ICS and ICCS guidelines, using appropriate terminology, providing indications for its performance with specific considerations for children, and proper interpretation of results. CONCLUSIONS: Cystometry can be used in children including newborn to evaluate lower urinary tract dysfunction.