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1.
Sci Rep ; 14(1): 20731, 2024 09 05.
Artículo en Inglés | MEDLINE | ID: mdl-39237660

RESUMEN

Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) is the leading cause of childhood chronic kidney failure and a significant cause of chronic kidney disease in adults. Genetic and environmental factors are known to influence CAKUT development, but the currently known disease mechanism remains incomplete. Our goal is to identify affected pathways and networks in CAKUT, and thereby aid in getting a better understanding of its pathophysiology. With this goal, the miRNome, peptidome, and proteome of over 30 amniotic fluid samples of patients with non-severe CAKUT was compared to patients with severe CAKUT. These omics data sets were made findable, accessible, interoperable, and reusable (FAIR) to facilitate their integration with external data resources. Furthermore, we analysed and integrated the omics data sets using three different bioinformatics strategies: integrative analysis with mixOmics, joint dimensionality reduction and pathway analysis. The three bioinformatics analyses provided complementary features, but all pointed towards an important role for collagen in CAKUT development and the PI3K-AKT signalling pathway. Additionally, several key genes (CSF1, IGF2, ITGB1, and RAC1) and microRNAs were identified. We published the three analysis strategies as containerized workflows. These workflows can be applied to other FAIR data sets and help gaining knowledge on other rare diseases.


Asunto(s)
Colágeno , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Humanos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Colágeno/metabolismo , Colágeno/genética , Biología Computacional/métodos , MicroARNs/genética , MicroARNs/metabolismo , Reflujo Vesicoureteral/genética , Reflujo Vesicoureteral/metabolismo , Femenino , Proteoma/metabolismo , Líquido Amniótico/metabolismo , Sistema Urinario/metabolismo , Multiómica , Anomalías Urogenitales
2.
Pediatr Surg Int ; 40(1): 222, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39136794

RESUMEN

PURPOSE: We investigated whether inflammatory cell infiltration (ICI), fibrosis, and mitochondrial viability of the neurogenic bladder urothelium are involved in the mechanism of persistent vesicoureteral reflux (VUR) after sigmoidocolocystoplasty (SCP). METHODS: Bladder biopsies obtained 1994-2023 from 62 neurogenic bladder patients were examined by hematoxylin and eosin for ICI, Masson's trichrome for fibrosis, and immunofluorescence for urothelial growth differentiation factor 15 (GDF15; a mitochondrial stress-responsive cytokine) (positive/negative) and heat shock protein 60 (HSP60; a mitochondrial matrix marker) (strong ≥ 50%/weak≤ 50%) expression. GDF15 + /weak HSP60 indicated compromised mitochondrial viability. Cystometry measured neobladder compliance/capacity. RESULTS: Mean ages (years) at SCP and bladder biopsies were 9.4 ± 4.6 and 14.2 ± 7.1, respectively. VUR was present in 38/62 patients (51 ureters) at SCP and resolved with SCP alone in 4/38 patients, with SCP and ureteroneocystostomy in 17/38, and persisted in 17/38. Fibrosis was significantly denser in GDF15 + (n = 24)/weak HSP60 (n = 31) compared with GDF15- (n = 38)/strong HSP60 (n = 31) (p < 0.001 and p < 0.01, respectively). Differences in ICI were significant for GDF15 + vs. GDF15- (p < 0.05) but not for HSP60. Patients with VUR after SCP had higher incidence of GDF15 + /weak HSP60 compared with cases without VUR (p < 0.05 and p < 0.001, respectively). CONCLUSION: Viability of mitochondria appears to be compromised with possible etiologic implications for VUR persisting after SCP.


Asunto(s)
Mitocondrias , Vejiga Urinaria Neurogénica , Urotelio , Reflujo Vesicoureteral , Humanos , Niño , Masculino , Vejiga Urinaria Neurogénica/cirugía , Vejiga Urinaria Neurogénica/etiología , Femenino , Reflujo Vesicoureteral/cirugía , Urotelio/metabolismo , Urotelio/patología , Adolescente , Mitocondrias/metabolismo , Preescolar , Vejiga Urinaria/cirugía , Vejiga Urinaria/patología , Colon Sigmoide/cirugía , Colon Sigmoide/patología , Biopsia , Estudios Retrospectivos , Factor 15 de Diferenciación de Crecimiento/metabolismo
3.
Sci Rep ; 14(1): 19344, 2024 08 20.
Artículo en Inglés | MEDLINE | ID: mdl-39164342

RESUMEN

There are currently no available data on the relationship between sonographic temporary nephromegaly in children during their first febrile urinary tract infection (fUTI) and recurrent fUTI. For this analysis, a multicenter retrospective cohort study of 343 children who underwent renal ultrasound during their first fUTI was conducted between 2013 and 2020. Sonographic temporary nephromegaly was defined as increased renal length during the initial fUTI, followed by normal renal length after antibiotic treatment. Compared with children without sonographic temporary nephromegaly (n = 307), the duration of fever and intravenous antibiotics was significantly longer, and C-reactive protein, creatinine, and the proportion of children who had recurrent fUTI were significantly higher, in those with sonographic temporary nephromegaly (n = 36). In an additional analysis of 100 patients who received voiding cystourethrography, a logistic regression model confirmed that the odds of vesicoureteral reflux (VUR) were significantly higher in children with temporary nephromegaly or those who experienced fUTI recurrence. In nine out of 16 children with VUR who had temporary nephromegaly, the reason for receiving voiding cystourethrography was recurrent fUTI. Our results suggest that sonographic temporary nephromegaly during an initial fUTI is predictive for recurrence and VUR, and that in children with temporary nephromegaly, VUR may be detectable before fUTI recurrence.


Asunto(s)
Fiebre , Riñón , Recurrencia , Ultrasonografía , Infecciones Urinarias , Humanos , Infecciones Urinarias/diagnóstico por imagen , Masculino , Femenino , Ultrasonografía/métodos , Estudios Retrospectivos , Preescolar , Lactante , Pronóstico , Riñón/diagnóstico por imagen , Riñón/patología , Reflujo Vesicoureteral/diagnóstico por imagen , Niño , Antibacterianos/uso terapéutico
4.
World J Urol ; 42(1): 499, 2024 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-39215768

RESUMEN

PURPOSE: Post-procedural urinary tract infections (ppUTIs) following voiding cystourethrography (VCUG) vary widely, with rates from 0 to 42%, though recent studies suggest rates typically below 5%. Verifying urine sterility before VCUG is traditionally done but questioned. This study assessed the 7-day ppUTI rate post-VCUG without prior urine sterility confirmation and identified associated risk factors. METHODS: A retrospective review of VCUG cases in children under three years at a pediatric hospital over two years was conducted. Exclusions included neuropathic bladder, bladder exstrophy, pre-VCUG urine cultures, and lost-to-follow-up cases. Achieving a ppUTI rate below 5% would support safe VCUG practice without pre-urine culture. RESULTS: Of 318 VCUGs performed on 300 children, 248 (78%) were males (8% circumcised) with a median age of 5 months. Retrograde VCUG was more common than suprapubic cystography (63% vs. 37%). Before the test, 33.6% received antibiotics, mostly prophylactically. Hydronephrosis was present in 66.4%, and 69% had a history of UTI. VCUG results were abnormal in 43% of cases: 85% had vesicoureteral reflux (VUR), 10% had posterior urethral valves (PUV), and 28% had other abnormalities. The 7-day ppUTI rate was 3.8%, with 67% of ppUTI cases having abnormal VCUG results versus 41% without ppUTI (p = 0.06). No significant risk factors for ppUTI were identified. CONCLUSIONS: Omitting systematic urine culture before VCUG was not associated with a high ppUTI rate, even in children with pre-existing urologic conditions or a history of UTI, indicating that VCUG can be safely performed without prior urine sterility confirmation. No risk factors for ppUTI were identified.


Asunto(s)
Cistografía , Infecciones Urinarias , Humanos , Infecciones Urinarias/epidemiología , Infecciones Urinarias/etiología , Estudios Retrospectivos , Masculino , Lactante , Femenino , Incidencia , Preescolar , Fiebre/epidemiología , Fiebre/etiología , Factores de Riesgo , Micción , Uretra/diagnóstico por imagen , Reflujo Vesicoureteral/epidemiología
5.
Surg Endosc ; 38(9): 5430-5437, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39078480

RESUMEN

BACKGROUND: Simulation-based training plays a significant role in surgical education, especially in minimally invasive pediatric surgery and urology. This study aimed to evaluate a novel 3D-printed model as training tool for endoscopic injection of bulking agent. METHODS: Forty-three attendees and ten teaching faculty members were invited to complete a post hoc questionnaire after completing training sessions using the Fish Tank Simulation Model (FTSM). The survey consisted of a 7-question 5-point Likert scale to assess the model's realism (face validity) and its effectiveness as training tool (content validity). RESULTS: Regarding the training status, 20/53 (37.7%) participants were fellow and/or specialist in pediatric surgery and 33/53 (62.3%) were surgeons in training. Their level of confidence in endoscopic injection procedure was defined as novice (< 10 procedures per year) in 33/53 (62.3%), intermediate (10-20 procedures per year) in 10/53 (18.9%), and expert (> 20 procedures per year) in 10/53 (18.9%). Regarding both face validity and content validity assessments, no statistically significant differences were found between scores given by novice vs intermediate/expert groups. Similarly, no statistically significant differences emerged between scores given by participant vs faculty groups assessing the content validity of the FTSM. The FTSM was considered a good teaching tool for beginners by 44/53 (83%) and for pediatric surgeons/urologists by 38/53 (71.7%). CONCLUSIONS: The 3D-printed Fish Tank Simulation Model proved to be a valuable, high-fidelity, easily accessible, cost-effective, hygienic, and domestic-use training tool for pediatric surgeons/urologists conducting the procedure. The model's user-friendly design and realistic environment enhanced learning opportunities for trainees, regardless of their experience level or training status. Nevertheless, further development is necessary, particularly in enhancing the realism of the ureteral hiatus and reproducing more complex anatomy, to make it beneficial for the training of advanced surgeons.


Asunto(s)
Competencia Clínica , Impresión Tridimensional , Entrenamiento Simulado , Reflujo Vesicoureteral , Humanos , Proyectos Piloto , Entrenamiento Simulado/métodos , Reflujo Vesicoureteral/terapia , Modelos Anatómicos , Inyecciones , Urología/educación , Endoscopía/educación , Endoscopía/métodos , Femenino
6.
World J Urol ; 42(1): 437, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39046550

RESUMEN

INTRODUCTION: Stents with anti-reflux properties have been previously described in various studies but not widely adopted. We designed, constructed and tested a novel umbrella-looking anti-reflux skirt on a double J stent at the level of the ureteral orifice in a previous ex-vivo study. This study serves as a proof of concept of testing this prototype in a porcine model. METHODS: 3 Yorkshire-Landrace pigs were put under general anaesthesia. Conventional bilateral retrograde stenting with white-colored double-J stents were performed. Deployment of anti-reflux skirt was performed unilaterally. Capsaicin mixed with methylene blue and saline were instilled in the bladder. Both stents were removed and methylene blue stain were inspected to assess the level of reflux. Bilateral stenting was performed again and stents/skirt prototype were left in-situ for 1 week. The procedure was repeated on Day 7 to re-test the anti-reflux property of the prototype after ureteral dilatation. RESULTS: Intraluminal reflux was evident, with methylene blue stain seen on the inner surface of the stents. Extraluminal reflux was proved with blue stain seen on the outer surface of the stents, both in undilated and dilated ureters. Study also proved the anti-reflux property of the skirt as the blue stain didn't go beyond the skirt, whereas the contralateral stent was stained up to proximal ureter. CONCLUSION: In this porcine in-vivo study, we elucidated that reflux occurred were both intraluminal and extraluminally. As a proof of concept, it also showed the anti-reflux property of a novel ureteral skirt.


Asunto(s)
Prueba de Estudio Conceptual , Diseño de Prótesis , Stents , Uréter , Reflujo Vesicoureteral , Animales , Porcinos , Uréter/cirugía , Modelos Animales de Enfermedad , Sus scrofa
7.
Sci Rep ; 14(1): 15252, 2024 07 02.
Artículo en Inglés | MEDLINE | ID: mdl-38956126

RESUMEN

This study aims to investigate the factors effective in predicting the persistence of reflux after the first subureteric transurethral injection (STING) of dextranomer/hyaluronic acid copolymer in pediatric patients with vesicoureteral reflux. The data of patients without a previous history of surgery to treat vesicoureteral reflux and who underwent STING for the first time between September 2011 and November 2020 were investigated retrospectively. After considering exclusion criteria, of 199 patients, 127 patients and 180 renal units were suitable for inclusion. A renal unit-based evaluation was made. Age < 61 months (univariate: p = 0.001, multivariate: p = 0.015, HR: 2.352 (1.181-4.686), OR (95% CI)), moderate reflux level (grade 3) (univariate: p < 0.001, multivariate: p = 0.019, HR: 2.703 (1.177-6.209), OR (95% CI)), DRF (differential renal function) < 45 (univariate: p = 0.020, multivariate: p = 0.047, HR: 1.992 (1.009-3.935), OR (95% CI)), and UDR (ureteral diameter ratio) > 0.15 (univariate: p < 0.001, multivariate: p = 0.005, HR: 2.786 (1.368-5.672), OR (95% CI)) were found predictors of reflux persistence after STING surgery both univariate and multivariate analysis. High reflux level (grade 4-5) was statistically significant in univariate analysis (p < 0.001) but not statistically significant in multivariate analysis (p = 0.215). In our study, UDR and DRF were found to be factors affecting reflux persistence. UDR and DRF should be considered in order to predict reflux resolution in patients who will undergo STING.


Asunto(s)
Dextranos , Ácido Hialurónico , Reflujo Vesicoureteral , Humanos , Reflujo Vesicoureteral/terapia , Ácido Hialurónico/administración & dosificación , Dextranos/administración & dosificación , Femenino , Masculino , Preescolar , Estudios Retrospectivos , Lactante , Niño , Inyecciones , Resultado del Tratamiento
8.
Int J Mol Sci ; 25(13)2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38999938

RESUMEN

The purpose of this study was to evaluate the spatiotemporal immunoexpression pattern of microtubule-associated protein 1 light chain 3 beta (LC3B), glucose-regulated protein 78 (GRP78), heat shock protein 70 (HSP70), and lysosomal-associated membrane protein 2A (LAMP2A) in normal human fetal kidney development (CTRL) and kidneys affected with congenital anomalies of the kidney and urinary tract (CAKUT). Human fetal kidneys (control, horseshoe, dysplastic, duplex, and hypoplastic) from the 18th to the 38th developmental week underwent epifluorescence microscopy analysis after being stained with antibodies. Immunoreactivity was quantified in various kidney structures, and expression dynamics were examined using linear and nonlinear regression modeling. The punctate expression of LC3B was observed mainly in tubules and glomerular cells, with dysplastic kidneys displaying distinct staining patterns. In the control group's glomeruli, LAMP2A showed a sporadic, punctate signal; in contrast to other phenotypes, duplex kidneys showed significantly stronger expression in convoluted tubules. GRP78 had a weaker expression in CAKUT kidneys, especially hypoplastic ones, while normal kidneys exhibited punctate staining of convoluted tubules and glomeruli. HSP70 staining varied among phenotypes, with dysplastic and hypoplastic kidneys exhibiting stronger staining compared to controls. Expression dynamics varied among observed autophagy markers and phenotypes, indicating their potential roles in normal and dysfunctional kidney development.


Asunto(s)
Autofagia , Chaperón BiP del Retículo Endoplásmico , Proteínas HSP70 de Choque Térmico , Riñón , Proteína 2 de la Membrana Asociada a los Lisosomas , Proteínas Asociadas a Microtúbulos , Humanos , Proteína 2 de la Membrana Asociada a los Lisosomas/metabolismo , Proteína 2 de la Membrana Asociada a los Lisosomas/genética , Riñón/metabolismo , Riñón/anomalías , Riñón/patología , Proteínas Asociadas a Microtúbulos/metabolismo , Proteínas HSP70 de Choque Térmico/metabolismo , Proteínas de Choque Térmico/metabolismo , Anomalías Urogenitales/metabolismo , Anomalías Urogenitales/patología , Sistema Urinario/metabolismo , Sistema Urinario/anomalías , Reflujo Vesicoureteral/metabolismo , Reflujo Vesicoureteral/patología
9.
Pediatr Surg Int ; 40(1): 184, 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-38995440

RESUMEN

PURPOSE: This study evaluated the outcome of pediatric patients with primary vesicoureteral reflux (VUR) and compared of the treatments between continued antibiotic prophylaxis (CAP) and endoscopic injection. METHODS: The clinical data of children diagnosed with primary vesicoureteral reflux from March 2015 to June 2020 who were treated with antibiotics or endoscopic injection were reviewed. Antibiotic was the first-chosen treatment after the diagnosis of VUR in children. Endoscopic treatment consisted of injection of dextran hyaluronic acid copolymer (DX/HA) into the ureteral opening under direct cystoscopy guidance. RESULTS: Fifty-two children (35 males, 17 females) were included in this study, and for a total 90 ureters (14 unilateral, 38 bilateral) were diagnosed with vesicoureteral reflux by Voiding cystourethrography (VCUG). Twenty-two children were treated with antibiotics (8 unilateral, 14 bilateral), for a total of 36 ureters; thirty children were treated by endoscopic injection (6 unilateral, 24 bilateral), for a total of 54 ureters. The injection surgery took 36 ± 17 min including duration of general anesthesia and circumcision and the hospital stay was 2.3 ± 1.3 days. All male patients underwent circumcision simultaneously. There were no drug and allergic reactions in the antibiotic group, and no postoperative complications occurred in the injection group. With 23 months (13-63 months) of mean follow-up, the resolution rate, defined as radiological disappearance of VUR, was 36.1% (13/36) in the antibiotic group and 57.4% (31/54) in the injection group (P = 0.048).Two cases of bilateral reflux in the injection group required a second injection before resolution could be achieved. Thus, the overall success rate of injection was 64.8% (35/54). 9 cases (9/18, 50%) in the antibiotic group had renal scars on DMSA scans, while this was seen in 20 cases (20/23, 86.9%) in the injection group. There was a statistically significant difference between the two groups (P = 0.010).The positive rates of ultrasound between the antibiotic group and the injection group were 45.5% (10/22) and 80.0% (24/30), respectively. There was a statistically significant difference between the two groups in positive rates of ultrasound (P = 0.010). CONCLUSIONS: Endoscopic injection is easy to operate with short surgical time and hospital stay, so it is a safe and feasible treatment. For the treatment of primary vesicoureteral reflux in children, the radiological resolution rate of endoscopic injection is better than antibiotic therapy. In this study, the presence of kidney scars on DMSA and the dilated of the collecting system on ultrasound are the indications for endoscopic injection.


Asunto(s)
Antibacterianos , Profilaxis Antibiótica , Cistoscopía , Dextranos , Ácido Hialurónico , Reflujo Vesicoureteral , Humanos , Reflujo Vesicoureteral/terapia , Reflujo Vesicoureteral/tratamiento farmacológico , Masculino , Femenino , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Ácido Hialurónico/administración & dosificación , Dextranos/administración & dosificación , Preescolar , Estudios Retrospectivos , Cistoscopía/métodos , Profilaxis Antibiótica/métodos , Lactante , Niño , Resultado del Tratamiento , Inyecciones/métodos
10.
Molecules ; 29(14)2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-39064873

RESUMEN

Kidney failures in infants are mostly caused by congenital anomalies of the kidney and urinary tract (CAKUT), which are among the most common congenital birth disorders worldwide when paired with cardiac abnormalities. People with CAKUT often have severe kidney failure as a result of a wide range of abnormalities that can occur alone or in conjunction with other syndromic disorders. In this study, we aimed to investigate the expression pattern of CAKUT candidate genes alpha-8 integrin (ITGA8) and Van Gogh-like 2 (VANGL2) in fetal tissues of healthy and CAKUT-affected kidneys using immunohistochemistry and immunofluorescence. We found that under CAKUT circumstances, the expressions of ITGA8 and VANGL2 are changed. Additionally, we showed that VANGL2 expression is constant during fetal aging, but ITGA8 expression varies. Moreover, compared to normal healthy kidneys (CTRL), ITGA8 is poorly expressed in duplex kidneys (DKs) and dysplastic kidneys (DYS), whereas VANGL2 is substantially expressed in dysplastic kidneys (DYS) and poorly expressed in hypoplastic kidneys (HYP). These results point to VANGL2 and ITGA8 as potential prognostic indicators for CAKUT malformations. Further research is necessary to explore the molecular mechanisms underlying this differential expression of ITGA8 and VANGL2.


Asunto(s)
Cadenas alfa de Integrinas , Riñón , Femenino , Humanos , Masculino , Cadenas alfa de Integrinas/metabolismo , Cadenas alfa de Integrinas/genética , Riñón/metabolismo , Riñón/anomalías , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Sistema Urinario/metabolismo , Sistema Urinario/anomalías , Anomalías Urogenitales/metabolismo , Anomalías Urogenitales/genética , Reflujo Vesicoureteral/metabolismo , Reflujo Vesicoureteral/genética
12.
J Pediatr Urol ; 20(4): 750.e1-750.e7, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38871546

RESUMEN

PURPOSE: Vesicoureteral reflux (VUR) grade has been used as a primary factor in assessing a child's risk of clinical outcomes. Unfortunately, grade has poor inter-observer reliability. We hypothesized that more objective and reliable VCUG parameters including the distal ureteral diameter ratio (UDR) and volume at onset of VUR (Vol) may either augment or replace the current grading system to provide more reliable prediction of clinical outcomes. MATERIALS AND METHODS: Multivariate clinical outcome models were analyzed to assess the impact on predictive accuracy by the addition of voiding cystourethrogram (VCUG) data including grade, UDR, and Vol, alone or in combinations. Clinical variables from retrospective review of 841 children's records included age, gender, presentation, VUR laterality, bowel and bladder dysfunction, history of febrile urinary tract infection (UTI), and number of UTIs. The primary outcomes assessed included VUR resolution or persistence and need for operative intervention. RESULTS: Grade, UDR, and Vol were independent predictors of resolution and operative intervention. Vol increased predictive accuracy in resolution models with grade or UDR alone; however, no significant difference occurred in models with the substitution of grade with UDR. CONCLUSIONS: A more reliable classification system for VUR, with improved predictive accuracy regarding clinical outcomes, may be developed incorporating UDR and Vol. Whether VUR grade can be completely replaced by Vol and UDR measurements requires further evaluation with larger number of patients.


Asunto(s)
Uréter , Vejiga Urinaria , Reflujo Vesicoureteral , Humanos , Reflujo Vesicoureteral/diagnóstico , Reflujo Vesicoureteral/diagnóstico por imagen , Femenino , Masculino , Estudios Retrospectivos , Uréter/diagnóstico por imagen , Preescolar , Vejiga Urinaria/diagnóstico por imagen , Vejiga Urinaria/patología , Lactante , Niño , Valor Predictivo de las Pruebas , Índice de Severidad de la Enfermedad , Cistografía/métodos , Adolescente , Pronóstico , Tamaño de los Órganos
13.
Curr Urol Rep ; 25(9): 233-239, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38888873

RESUMEN

PURPOSE OF REVIEW: Traditional surgical management for urinary incontinence and vesicoureteral reflux often requires complex reconstructive surgery and extended hospitalizations. Since the introduction of endoscopic bulking agents in 1973, there has been increasing interest in the use of endoscopic injection (EI) and bulking for the treatment of a variety of pediatric urologic disorders. The purpose of this review is to summarize the most recent literature addressing the use of bulking agents in pediatric urology. RECENT FINDINGS: The most recent literature has focused primarily on the use of EI of bulking agents at the bladder neck for the treatment of urinary incontinence. Other uses of EI of bulking agents has focused on the treatment of vesicoureteral reflux (VUR) in patients with anatomic abnormalities or treatment of incontinence catheterizable channels. The development of advanced techniques for endoscopic injection along with safe, stable bulking agents has allowed for the treatment of a variety of urologic conditions. This minimally invasive procedure offers an additional tool for the pediatric urologist's armamentarium in the treatment of urinary incontinence and VUR.


Asunto(s)
Incontinencia Urinaria , Reflujo Vesicoureteral , Humanos , Reflujo Vesicoureteral/terapia , Reflujo Vesicoureteral/cirugía , Niño , Inyecciones , Materiales Biocompatibles/administración & dosificación , Ácido Hialurónico/administración & dosificación , Ácido Hialurónico/uso terapéutico
14.
Arch Esp Urol ; 77(4): 378-384, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38840280

RESUMEN

BACKGROUND: Bilateral vesicoureteral reflux (VUR) has been associated with poor long-term prognosis, and research focusing exclusively on its effect on urinary bladder function is lacking. This study aims to assess the urodynamic characteristics of children with bilateral VUR and identify factors influencing renal function. METHODS: A retrospective analysis was performed on children diagnosed with bilateral VUR who underwent urodynamic examination in the outpatient department of our institution from January 2019 to January 2023. All patients underwent comprehensive assessments, including voiding cystourethrography, urinary system ultrasound and urodynamic examination, to analyse the urodynamic features associated with different clinical characteristics. RESULTS: The study included 148 children with bilateral VUR, amongst whom 92 (62.2%) exhibited urodynamic abnormalities, including idiopathic detrusor overactivity (DO) in 30 cases (20.3%) and dysfunctional voiding (DV) in 58 cases (39.2%). DV was prevalent in children under 5 years of age, whereas idiopathic DO was predominantly observed in children older than 2 years of age. Children older than 5 years of age exhibited a trend towards reduced bladder volume, whereas those younger than 2 years of age often had increased bladder volume and residual urine. Multivariate analysis identified bilateral severe VUR as an independent risk factor for abnormal estimated glomerular filtration rate. CONCLUSIONS: DV tends to be more common in younger children with larger bladder volumes and increased residual urine than in older children. By contrast, older children are more susceptible to idiopathic DO associated with smaller bladder volumes than younger children. Bilateral severe reflux increases the likelihood of renal functional abnormalities, which appear to be a consequence of congenital scarring rather than abnormalities in bladder function.


Asunto(s)
Urodinámica , Reflujo Vesicoureteral , Humanos , Reflujo Vesicoureteral/complicaciones , Reflujo Vesicoureteral/fisiopatología , Estudios Retrospectivos , Masculino , Femenino , Preescolar , Niño , Lactante
15.
Genes (Basel) ; 15(6)2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38927638

RESUMEN

Approximately half of the cases of chronic kidney disease (CKD) in childhood are caused by congenital anomalies of the kidney and urinary tract (CAKUT). Specific genes were identified as having significant importance in regard to the underlying genetic factors responsible for the CAKUT phenotype, and in our research, we focused on analyzing and comparing the expression levels of ectodysplasin A2 receptor (EDA2R), protocadherin9 (PCDH9), and TNF receptor-associated factor 7 (TRAF7) proteins in the cortex and medulla of healthy control kidneys during developmental phases 2, 3, and 4. We also performed an analysis of the area percentages of the mentioned proteins in the cortical and medullary sections of healthy embryonic and fetal kidneys compared to those affected by CAKUT, including duplex kidneys (DK), horseshoe kidneys (HK), hypoplastic kidneys (HYP), and dysplastic kidneys (DYS). We found that the CAKUT candidate gene proteins EDA2R, PCDH9, and TRAF7 are all expressed during normal human kidney development stages. In DYS, the expression of EDA2R was higher than in normal kidneys, likely due to EDA2R's role in apoptosis, which was upregulated in specific cases and could possibly contribute to the formation of DYS. The expression of PCDH9 was lower in HK, which can be attributed to the possible role of PCDH9 in cell migration suppression. Decreased PCDH9 expression is linked to increased cell migration, potentially contributing to the development of HK. The level of TRAF7 expression was reduced in all examined kidney disorders compared to normal kidneys, suggesting that this reduction might be attributed to the crucial role of TRAF7 in the formation of endothelium and ciliogenesis, both of which are essential for normal kidney development. Further research is required to ascertain the function of these proteins in both the typical development of the kidney and in CAKUT.


Asunto(s)
Cadherinas , Riñón , Anomalías Urogenitales , Reflujo Vesicoureteral , Humanos , Cadherinas/genética , Cadherinas/metabolismo , Regulación del Desarrollo de la Expresión Génica , Riñón/metabolismo , Riñón/anomalías , Riñón/crecimiento & desarrollo , Riñón/embriología , Protocadherinas , Sistema Urinario/anomalías , Sistema Urinario/metabolismo , Anomalías Urogenitales/genética , Anomalías Urogenitales/patología , Reflujo Vesicoureteral/genética , Reflujo Vesicoureteral/patología
17.
EMBO Rep ; 25(7): 3040-3063, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38849673

RESUMEN

Polarized vesicular trafficking directs specific receptors and ion channels to cilia, but the underlying mechanisms are poorly understood. Here we describe a role for DLG1, a core component of the Scribble polarity complex, in regulating ciliary protein trafficking in kidney epithelial cells. Conditional knockout of Dlg1 in mouse kidney causes ciliary elongation and cystogenesis, and cell-based proximity labeling proteomics and fluorescence microscopy show alterations in the ciliary proteome upon loss of DLG1. Specifically, the retromer-associated protein SDCCAG3, IFT20, and polycystin-2 (PC2) are reduced in the cilia of DLG1-deficient cells compared to control cells. This phenotype is recapitulated in vivo and rescuable by re-expression of wild-type DLG1, but not a Congenital Anomalies of the Kidney and Urinary Tract (CAKUT)-associated DLG1 variant, p.T489R. Finally, biochemical approaches and Alpha Fold modelling suggest that SDCCAG3 and IFT20 form a complex that associates, at least indirectly, with DLG1. Our work identifies a key role for DLG1 in regulating ciliary protein composition and suggests that ciliary dysfunction of the p.T489R DLG1 variant may contribute to CAKUT.


Asunto(s)
Proteínas Portadoras , Cilios , Homólogo 1 de la Proteína Discs Large , Canales Catiónicos TRPP , Animales , Cilios/metabolismo , Canales Catiónicos TRPP/metabolismo , Canales Catiónicos TRPP/genética , Ratones , Homólogo 1 de la Proteína Discs Large/metabolismo , Proteínas Portadoras/metabolismo , Proteínas Portadoras/genética , Humanos , Transporte de Proteínas , Ratones Noqueados , Riñón/metabolismo , Células Epiteliales/metabolismo , Unión Proteica , Reflujo Vesicoureteral/metabolismo , Reflujo Vesicoureteral/genética , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Anomalías Urogenitales
20.
Int Urol Nephrol ; 56(9): 2825-2831, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38696036

RESUMEN

AIM: We aimed to study the presence of lower urinary tract dysfunction (LUTD) and those objective parameters obtained from voiding diary (VD), uroflowmetric (UF) and postvoiding residual urine (PVR) and voiding dysfunction symptom score (VDSS) as possible factors effecting the success rate on STING to correct VUR. MATERIALS AND METHODS: Children who underwent STING for the first time due to low-moderate (I-III) grade of VUR were evaluated retrospectively. All children diagnosed with VUR were routinely evaluated for LUTD with VD, UF, PVR and VDSS. Children with LUTD were treated with urotherapy and appropriate medical treatment. Each system with VUR was accepted a renal unit and divided into two groups according to the presence of postoperative VUR: Group 1 no VUR, and Group 2 unresolved VUR. Demographic characteristics, DMSA scintigraphy findings, PVR, VDSS and parameters of VD and UF were compared. RESULTS: 80 children (73 (91.3%) girl, 7 (8.8%) boy) with a total of 112 unit were detected. There were 93 (83%) units in group 1 and 19 (17%) in group 2. No difference was observed in voiding frequency and urinary incontinence in VD, flow pattern, maximum flow rate, MBC/EBC maximum bladder capacity/expected bladder capacity in UF, PVR and VDSS between two groups. 21 (26.25%) children were diagnosed and treated for LUTD and STING was successful in 21 (84%) of 25 units. CONCLUSION: We believe that effectively treated preoperative LUTD provides comparable STING success rate for correcting low- to moderate-grade vesicoureteral reflux (VUR) in the short term.


Asunto(s)
Síntomas del Sistema Urinario Inferior , Reflujo Vesicoureteral , Humanos , Reflujo Vesicoureteral/terapia , Femenino , Masculino , Estudios Retrospectivos , Preescolar , Síntomas del Sistema Urinario Inferior/etiología , Síntomas del Sistema Urinario Inferior/terapia , Síntomas del Sistema Urinario Inferior/fisiopatología , Niño , Resultado del Tratamiento , Ácido Hialurónico/administración & dosificación , Urodinámica , Inyecciones , Uréter , Lactante , Índice de Severidad de la Enfermedad
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