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1.
J Urol ; 209(6): 1194-1201, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36812398

RESUMO

PURPOSE: Little is known about the impact of ureteral stents on youth having stone surgery. We evaluated the association of ureteral stent placement before or concurrent with ureteroscopy and shock wave lithotripsy with emergency department visits and opioid prescriptions among pediatric patients. MATERIALS AND METHODS: We conducted a retrospective cohort study of individuals aged 0-24 years who underwent ureteroscopy or shock wave lithotripsy from 2009-2021 at 6 hospitals in PEDSnet, a research network that aggregates electronic health record data from children's health systems in the United States. The exposure, primary ureteral stent placement, was defined as a stent placed concurrent with or within 60 days before ureteroscopy or shock wave lithotripsy. Associations between primary stent placement and stone-related ED visits and opioid prescriptions within 120 days of the index procedure were evaluated with mixed-effects Poisson regression. RESULTS: Two-thousand ninety-three patients (60% female; median age 15 years, IQR 11-17) had 2,477 surgical episodes; 2,144 were ureteroscopy and 333 were shock wave lithotripsy. Primary stents were placed in 1,698 (79%) ureteroscopy episodes and 33 (10%) shock wave lithotripsy episodes. Ureteral stents were associated with a 33% higher rate of emergency department visits (IRR 1.33; 95% CI 1.02-1.73) and a 30% higher rate of opioid prescriptions (IRR 1.30; 95% CI 1.10-1.53). The magnitudes of both associations were greater for shock wave lithotripsy. Results were similar for age <18 and were lost when restricted to concurrent stent placement. CONCLUSIONS: Primary ureteral stent placement was associated with more frequent emergency department visits and opioid prescriptions, driven by pre-stenting. These results support elucidating situations where stents are not necessary for youth with nephrolithiasis.


Assuntos
Cálculos Renais , Litotripsia , Cálculos Ureterais , Humanos , Feminino , Adolescente , Criança , Masculino , Ureteroscopia/métodos , Analgésicos Opioides/uso terapêutico , Estudos Retrospectivos , Cálculos Renais/cirurgia , Serviço Hospitalar de Emergência , Stents , Cálculos Ureterais/cirurgia , Resultado do Tratamento
2.
World J Urol ; 41(12): 3801-3806, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37902862

RESUMO

PURPOSE: To evaluate whether X, formerly known as Twitter, is being used effectively to advance the goals of International Volunteers in Urology (IVUmed). How is X activity associated with end-user engagement? METHODS: Monthly analytics of the X account @IVUmed were reviewed between September 2014 and November 2022 using https://analytics.twitter.com/ . Outcomes included tweets, mentions, impressions, engagements, interactions, followers, and profile visits. Statistical analysis using Mann-Whitney U test and Spearman's rank-order correlation was performed. Top tweet content between December 2020 and November 2022 was also analyzed and assigned one of seven different categories: research, workshops, mission statement, educational materials, fundraising, individual spotlight, and other. RESULTS: Of @IVUmed's 1668 followers, 1334 (80.0%) were individuals. One thousand one hundred twenty-six (84.4%) individuals listed their locations with the majority (79.8%) residing in high-income countries. Tweet impressions have increased over time; they were significantly higher (p < 0.01) on average after the onset of COVID-19 in March 2020. From December 2020 to November 2022, new followers were positively correlated with tweet impressions (p < 0.01), total mentions (p < 0.01), and profile visits (p < 0.01). Profile visits were positively correlated with total tweets (p < 0.01). The content categories for monthly top tweets that proportionally garnered the most engagements were workshops (50%) and individual spotlight (29%), despite not being the most tweeted about content categories. CONCLUSION: Non-profit organizations wishing to increase their web-based outreach can benefit from increased primary X activity. While not evaluated in this study, it may also improve fundraising capabilities. Nevertheless, periodic review of account activity is important to ensure engagement of the targeted audience.


Assuntos
Mídias Sociais , Urologia , Humanos , Saúde Global , Marketing
3.
Eur J Pediatr ; 182(9): 4027-4036, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37392234

RESUMO

The rarity of primary hyperoxaluria (PH) challenges our understanding of the disease. The purpose of our study was to describe the course of clinical care in a United States cohort of PH pediatric patients, highlighting health service utilization. We performed a retrospective cohort study of PH patients < 18 years old in the PEDSnet clinical research network from 2009 to 2021. Outcomes queried included diagnostic imaging and testing related to known organ involvement of PH, surgical and medical interventions specific to PH-related renal disease, and select PH-related hospital service utilization. Outcomes were evaluated relative to cohort entrance date (CED), defined as date of first PH-related diagnostic code. Thirty-three patients were identified: 23 with PH type 1; 4 with PH type 2; 6 with PH type 3. Median age at CED was 5.0 years (IQR 1.4, 9.3 years) with the majority being non-Hispanic white (73%) males (70%). Median follow-up between CED and most recent encounter was 5.1 years (IQR 1.2, 6.8). Nephrology and Urology were the most common specialties involved in care, with low utilization of other sub-specialties (12%-36%). Most patients (82%) had diagnostic imaging used to evaluate kidney stones; 11 (33%) had studies of extra-renal involvement. Stone surgery was performed in 15 (46%) patients. Four patients (12%) required dialysis, begun in all prior to CED; four patients required renal or renal/liver transplant.    Conclusion: In this large cohort of U.S. PH children, patients required heavy health care utilization with room for improvement in involving multi-disciplinary specialists. What is Known: • Primary hyperoxaluria (PH) is rare with significant implications on patient health. Typical involvement includes the kidneys; however, extra-renal manifestations occur. • Most large population studies describe clinical manifestations and involve registries. What is New: • We report the clinical journey, particularly related to diagnostic studies, interventions, multispecialty involvement, and hospital utilization, of a large cohort of PH pediatric patients in the PEDSnet clinical research network. • There are missed opportunities, particularly in that of specialty care, that could help in the diagnosis, treatment, and even prevention of known clinical manifestations.

4.
Curr Urol Rep ; 23(6): 113-127, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35441976

RESUMO

PURPOSE OF REVIEW: While antibiotics have been a staple in the management and even prevention of urinary tract infections (UTIs), it is not without significant consequences due to intolerance and development of antibiotic resistant bacteria. These concerns necessitate alternatives to antibiotic use in the management of pediatric UTIs. This review seeks to evaluate non-antibiotic means of preventing UTI in the pediatric population. RECENT FINDINGS: The search for preventative alternatives to antibiotics has included D-mannose, cranberry, and probiotics. These products similarly work through competitive inhibition of uropathogens in the urinary tract. Pediatric studies exist highlighting the use of cranberry extract/juice and probiotics in UTI prevention, although significant heterogeneity amongst studies have limited overarching recommendations for their use. Data of D-mannose use is extrapolated from adult literature. More studies are required in the utility of each treatment, with some emphasis on larger sample sizes and clarifications regarding dosing and formulation.


Assuntos
Probióticos , Infecções Urinárias , Vaccinium macrocarpon , Adulto , Antibacterianos/uso terapêutico , Criança , Feminino , Humanos , Masculino , Manose/uso terapêutico , Fitoterapia , Extratos Vegetais/uso terapêutico , Probióticos/uso terapêutico , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/prevenção & controle
5.
Pediatr Nephrol ; 36(1): 111-118, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32583045

RESUMO

BACKGROUND: Obstructive uropathy (OU) is a leading cause of pediatric kidney injury. Accurate prediction of kidney disease progression may improve clinical outcomes. We aimed to examine discrimination and accuracy of a validated kidney failure risk equation (KFRE), previously developed in adults, in children with OU. METHODS: We identified 118 children with OU and an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 in the Chronic Kidney Disease in Children study, a national, longitudinal, observational cohort. Each patient's 5-year risk of kidney failure was estimated using baseline data and published parameters for the 4- and 8-variable KFREs. Discriminative ability of the KFRE was estimated using the C statistic for time-to-event analysis. Sensitivity and specificity were evaluated across varying risk thresholds. RESULTS: Among the 118 children, 100 (85%) were boys, with median baseline age of 10 years (interquartile range, 6-14). Median eGFR was 42 mL/min/1.73m 2 (32-53), with a median follow-up duration of 4.5 years (2.7-7.2); 23 patients (19.5%) developed kidney failure within 5 years. The 4-variable KFRE discriminated kidney failure risk with a C statistic of 0.75 (95% CI, 0.68-0.82). A 4-variable risk threshold of ≥ 30% yielded 82.6% sensitivity and 75.0% specificity. Results were similar using the 8-variable KFRE. CONCLUSIONS: In children with OU, the KFRE discriminated the 5-year risk of kidney failure at C statistic values lower than previously published in adults but comparable with suboptimal values reported in the overall CKiD population. The 8-variable equation did not improve model discrimination or accuracy, suggesting the need for continued research into additional, disease-specific markers.


Assuntos
Falência Renal Crônica , Insuficiência Renal Crônica , Criança , Pré-Escolar , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Humanos , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/etiologia , Masculino , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia
6.
Pediatr Nephrol ; 35(10): 1907-1914, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32444926

RESUMO

BACKGROUND: Congenital obstructive uropathy (OU) is a leading cause of pediatric kidney failure, representing a unique mechanism of injury, in part from renal tubular stretch and ischemia. Tubular injury biomarkers have potential to improve OU-specific risk stratification. METHODS: Patients with OU were identified in the Chronic Kidney Disease in Children (CKiD) study. "Cases" were defined as individuals receiving any kidney replacement therapy (KRT), while "controls" were age- and time-on-study matched and KRT free at last study visit. Urine and plasma neutrophil gelatinase-associated lipocalin (NGAL), interleukin 18 (IL-18), and liver-type fatty acid-binding protein (L-FABP) levels were measured at enrollment and annually and compared between cases and controls. Urine values were normalized to urine creatinine. RESULTS: In total, 22 cases and 22 controls were identified, with median (interquartile range) ages of 10.5 (9.0-13.0) and 15.9 (13.9-16.9) years at baseline and outcome, respectively. At enrollment there were no differences noted between cases and controls for any urine (u) or plasma (p) biomarker measured. However, the mean pNGAL and uL-FABP/creatinine increased throughout the study period in cases (15.38 ng/ml per year and 0.20 ng/ml per mg/dl per year, respectively, p = 0.01 for both) but remained stable in controls. This remained constant after controlling for baseline glomerular filtration rate (GFR). CONCLUSIONS: In children with OU, pNGAL and uL-FABP levels increased over the 5 years preceding KRT; independent of baseline GFR. Future studies are necessary to identify optimal cutoff values and to determine if these markers outperform current clinical predictors.


Assuntos
Proteínas de Ligação a Ácido Graxo/urina , Lipocalina-2/urina , Insuficiência Renal Crônica/diagnóstico , Terapia de Substituição Renal/estatística & dados numéricos , Obstrução Uretral/complicações , Adolescente , Biomarcadores/sangue , Biomarcadores/urina , Estudos de Casos e Controles , Criança , Creatinina/urina , Proteínas de Ligação a Ácido Graxo/sangue , Feminino , Seguimentos , Taxa de Filtração Glomerular/fisiologia , Humanos , Interleucina-18/sangue , Interleucina-18/urina , Rim/fisiopatologia , Lipocalina-2/sangue , Estudos Longitudinais , Masculino , Prognóstico , Estudos Prospectivos , Valores de Referência , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/terapia , Insuficiência Renal Crônica/urina , Medição de Risco/métodos , Obstrução Uretral/sangue , Obstrução Uretral/congênito , Obstrução Uretral/urina
7.
Am J Physiol Renal Physiol ; 317(3): F757-F766, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31322419

RESUMO

Congenital urinary tract obstruction (UTO) is the leading cause of chronic kidney disease in children; however, current management strategies do not safeguard against progression to end-stage renal disease, highlighting the need for interventions to limit or reverse obstructive nephropathy. Experimental UTO triggers renal urothelial remodeling that culminates in the redistribution of basal keratin 5-positive (Krt5+) renal urothelial cells (RUCs) and the generation of uroplakin-positive (Upk)+ RUCs that synthesize a protective apical urothelial plaque. The cellular source of Upk+ RUCs is currently unknown, limiting the development of strategies to promote renal urothelial remodeling as a therapeutic approach. In the present study, we traced the origins of adult Upk+ RUCs during normal development and in response to UTO. Fate mapping analysis demonstrated that adult Upk+ RUCs derive from embryonic and neonatal Krt5+ RUCs, whereas Krt5+ RUCs lose this progenitor capacity and become lineage restricted by postnatal day 14. However, in response to UTO, postnatal day 14-labeled adult Krt5+ RUCs break their lineage restriction and robustly differentiate into Upk+ RUCs. Thus, Krt5+ RUCs drive renal urothelial formation during normal ontogeny and after UTO by differentiating into Upk+ RUCs in a temporally restricted manner.


Assuntos
Diferenciação Celular , Células Epiteliais/metabolismo , Queratina-15/metabolismo , Nefropatias/metabolismo , Rim/metabolismo , Regeneração , Células-Tronco/metabolismo , Obstrução Ureteral/complicações , Urotélio/metabolismo , Animais , Linhagem da Célula , Modelos Animais de Doenças , Células Epiteliais/patologia , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Idade Gestacional , Queratina-15/genética , Rim/crescimento & desenvolvimento , Rim/patologia , Nefropatias/etiologia , Nefropatias/patologia , Nefropatias/fisiopatologia , Masculino , Camundongos Knockout , Organogênese , Células-Tronco/patologia , Uroplaquinas/metabolismo , Urotélio/crescimento & desenvolvimento , Urotélio/patologia
8.
Pediatr Nephrol ; 34(3): 443-448, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30317433

RESUMO

BACKGROUND: Obstructive uropathy (OU) is a common cause of end-stage renal disease (ESRD) in children. Children who escape the newborn period with mild-to-moderate chronic kidney disease (CKD) continue to be at increased risk. The predictive ability of clinically available markers throughout childhood is poorly defined. METHODS: Patients with OU were identified in the Chronic Kidney Disease in Children Study. The primary outcome of interest was renal replacement therapy (RRT) (cases). Controls were age matched and defined as patients within the OU cohort who did not require RRT during study follow-up. RESULTS: In total, 27 cases and 41 age-matched controls were identified. Median age at baseline and age at outcome measurement were 10 vs. 16 years, respectively. First available glomerular filtration rate (GFR) (36.9 vs. 53.5 mL/min per 1.73 m2), urine protein/creatinine (Cr) (0.40 vs. 0.22 mg/mg) and microalbumin/Cr (0.58 vs. 0.03 mg/mg), and serum CO2 (20 vs. 22 mmol/L) and hemoglobin (12.4 vs. 13.2 g/dL) differed significantly between cases and controls, respectively. GFR declined 3.07 mL/min per 1.73 m2/year faster in cases compared to that in controls (p < 0.0001). Urine protein/Cr and microalbumin/Cr increased by 0.16 and 0.11 per year more in cases compared to those in controls, respectively (p ≤ 0.001 for both). Serum phosphate increased by 0.11 mg/dL and serum albumin and hemoglobin decreased by 0.04 (g/dL) and 0.14 (g/dL) per year more for cases compared to those for controls, respectively (p < 0.05 for all). CONCLUSIONS: Age-specific baseline and longitudinal measures of readily available clinical measures predict progression to ESRD in children with mild-to-moderate CKD from OU.


Assuntos
Falência Renal Crônica/diagnóstico , Terapia de Substituição Renal/estatística & dados numéricos , Obstrução Ureteral/complicações , Refluxo Vesicoureteral/complicações , Adolescente , Biomarcadores/sangue , Biomarcadores/urina , Estudos de Casos e Controles , Criança , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Humanos , Falência Renal Crônica/etiologia , Falência Renal Crônica/terapia , Testes de Função Renal/métodos , Estudos Longitudinais , Masculino , Estudos Prospectivos , Estados Unidos/epidemiologia , Obstrução Ureteral/sangue , Obstrução Ureteral/congênito , Obstrução Ureteral/urina , Refluxo Vesicoureteral/sangue , Refluxo Vesicoureteral/congênito , Refluxo Vesicoureteral/urina
9.
Am J Physiol Renal Physiol ; 315(4): F1019-F1031, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-29897287

RESUMO

Urinary tract obstruction represents a common cause of kidney injury across the human life span, resulting in chronic kidney disease and end-stage renal disease. Yet, the extent of obstructive renal damage can be heterogeneous between individuals, implying the existence of unknown mechanisms that protect against or accelerate kidney injury. In this study, we investigated the role of urothelial remodeling in renal adaptation during congenital and acquired obstruction. In the Megabladder ( Mgb-/-) model of congenital obstruction and unilateral ureteral ligation model of acute obstruction, progressive hydronephrosis is strongly associated with dynamic reorganization of the renal urothelium, which elaborates a continuous uroplakin (Upk) plaque. This led us to postulate that the Upk plaque prevents parenchymal injury during urinary tract obstruction. To test this hypothesis, we interbred Mgb-/- and Upk1b-/- mice, which lack the critical Upk1b subunit for Upk plaque formation. Upk1b-/-; Mgb-/- mice experienced an accelerated onset of bilateral hydronephrosis with severe (>67%) parenchymal loss, leading to renal failure and mortality in adolescence. To investigate the function of the renal Upk plaque during acute obstruction, we destabilized the Upk plaque by Upk1b deletion or genetically depleted Upk+ cells following unilateral ureteral obstruction. Both of these strategies accelerated renal parenchymal loss following ureteral ligation, attesting to a conserved, stabilizing role for Upk plaque deposition in the acutely obstructed kidney. In aggregate, these complementary experiments provide the first evidence that the Upk plaque confers an essential, protective adaptation to preserve renal parenchymal integrity during congenital and acquired urinary tract obstruction.


Assuntos
Rim/patologia , Obstrução Ureteral/complicações , Uroplaquinas/metabolismo , Urotélio/patologia , Animais , Modelos Animais de Doenças , Hidronefrose/fisiopatologia , Rim/fisiopatologia , Falência Renal Crônica/complicações , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Insuficiência Renal/complicações , Insuficiência Renal/patologia , Urotélio/fisiopatologia
10.
Kidney Int ; 94(3): 455-457, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30143065

RESUMO

Sex differences in urinary tract infection (UTI) susceptibility and severity are known, but have historically focused on anatomic differences between males and females. Until recently, experimental UTI has been limited to female animals due to ease of transurethral bladder catheterization. Olson and colleagues have developed a model of experimental UTI independent of sex that relies on direct bladder inoculation and thus permits investigation of sex differences in UTI susceptibility. They now build upon their prior work in this model by implicating androgens as drivers of tubular invasion by uropathogenic Escherichia coli, which form luminal bacterial communities preceding renal abscess formation.


Assuntos
Abscesso , Androgênios , Animais , Modelos Animais de Doenças , Infecções por Escherichia coli , Feminino , Masculino , Pielonefrite , Infecções Urinárias , Escherichia coli Uropatogênica
11.
Kidney Int ; 93(6): 1320-1329, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29475562

RESUMO

The signaling networks regulating antimicrobial activity during urinary tract infection (UTI) are incompletely understood. Interleukin-6 (IL-6) levels increase with UTI severity, but the specific contributions of IL-6 to host immunity against bacterial uropathogens are unknown. To clarify this we tested whether IL-6 activates the Stat3 transcription factor, to drive a program of antimicrobial peptide gene expression in infected urothelium during UTI. Transurethral inoculation of uropathogenic Escherichia coli led to IL-6 secretion, urothelial Stat3 phosphorylation, and activation of antimicrobial peptide transcription, in a Toll-like receptor 4-dependent manner in a murine model of cystitis. Recombinant IL-6 elicited Stat3 phosphorylation in primary urothelial cells in vitro, and systemic IL-6 administration promoted urothelial Stat3 phosphorylation and antimicrobial peptide expression in vivo. IL-6 deficiency led to decreased urothelial Stat3 phosphorylation and antimicrobial peptide mRNA expression following UTI, a finding mirrored by conditional Stat3 deletion. Deficiency in IL-6 or Stat3 was associated with increased formation of intracellular bacterial communities, and exogenous IL-6 reversed this phenotype in IL-6 knockout mice. Moreover, chronic IL-6 depletion led to increased renal bacterial burden and severe pyelonephritis in C3H/HeOuJ mice. Thus, IL-6/Stat3 signaling drives a transcriptional program of antimicrobial gene expression in infected urothelium, with key roles in limiting epithelial invasion and ascending infection.


Assuntos
Cistite/metabolismo , Infecções por Escherichia coli/metabolismo , Escherichia coli/patogenicidade , Interleucina-6/metabolismo , Fator de Transcrição STAT3/metabolismo , Bexiga Urinária/metabolismo , Infecções Urinárias/metabolismo , Urotélio/metabolismo , Animais , Linhagem Celular , Cistite/genética , Cistite/microbiologia , Modelos Animais de Doenças , Infecções por Escherichia coli/genética , Infecções por Escherichia coli/microbiologia , Feminino , Hepcidinas/genética , Hepcidinas/metabolismo , Interações Hospedeiro-Patógeno , Humanos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Associadas a Pancreatite/genética , Proteínas Associadas a Pancreatite/metabolismo , Fosforilação , Fator de Transcrição STAT3/deficiência , Fator de Transcrição STAT3/genética , Transdução de Sinais , Receptor 4 Toll-Like/metabolismo , Bexiga Urinária/microbiologia , Infecções Urinárias/genética , Infecções Urinárias/microbiologia , Urotélio/microbiologia
14.
Am J Physiol Renal Physiol ; 312(1): F43-F53, 2017 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-27760770

RESUMO

Acquired renal scarring occurs in a subset of patients following febrile urinary tract infections and is associated with hypertension, proteinuria, and chronic kidney disease. Limited knowledge of histopathology, immune cell recruitment, and gene expression changes during pyelonephritis restricts the development of therapies to limit renal scarring. Here, we address this knowledge gap using immunocompetent mice with vesicoureteral reflux. Transurethral inoculation of uropathogenic Escherichia coli in C3H/HeOuJ mice leads to renal mucosal injury, tubulointerstitial nephritis, and cortical fibrosis. The extent of fibrosis correlates most significantly with inflammation at 7 and 28 days postinfection. The recruitment of neutrophils and inflammatory macrophages to infected kidneys is proportional to renal bacterial burden. Transcriptome analysis reveals molecular signatures associated with renal ischemia-reperfusion injury, immune cell chemotaxis, and leukocyte activation. This murine model recapitulates the cardinal histopathological features observed in humans with acquired renal scarring following pyelonephritis. The integration of histopathology, quantification of cellular immune influx, and unbiased transcriptional profiling begins to define potential mechanisms of tissue injury during pyelonephritis in the context of an intact immune response. The clear relationship between inflammatory cell recruitment and fibrosis supports the hypothesis that acquired renal scarring arises as a consequence of excessive host inflammation and suggests that immunomodulatory therapies should be investigated to reduce renal scarring in patients with pyelonephritis.


Assuntos
Cicatriz/metabolismo , Escherichia coli/isolamento & purificação , Inflamação/microbiologia , Rim/microbiologia , Pielonefrite/microbiologia , Refluxo Vesicoureteral/imunologia , Animais , Modelos Animais de Doenças , Feminino , Fibrose/imunologia , Fibrose/microbiologia , Inflamação/imunologia , Inflamação/patologia , Rim/patologia , Camundongos , Camundongos Endogâmicos C3H , Nefrite Intersticial/imunologia , Nefrite Intersticial/microbiologia , Nefrite Intersticial/patologia , Pielonefrite/imunologia , Traumatismo por Reperfusão/microbiologia , Traumatismo por Reperfusão/patologia , Refluxo Vesicoureteral/microbiologia
16.
Kidney Int ; 89(3): 612-24, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26880456

RESUMO

Proper development and maintenance of urothelium is critical to its function. Uroplakins are expressed in developing and mature urothelium where they establish plaques associated with the permeability barrier. Their precise functional role in development and disease is unknown. Here, we disrupted Upk1b in vivo where its loss resulted in urothelial plaque disruption in the bladder and kidney. Upk1b(RFP/RFP) bladder urothelium appeared dysplastic with expansion of the progenitor cell markers, Krt14 and Krt5, increased Shh expression, and loss of terminal differentiation markers Krt20 and uroplakins. Upk1b(RFP/RFP) renal urothelium became stratified with altered cellular composition. Upk1b(RFP/RFP) mice developed age-dependent progressive hydronephrosis. Interestingly, 16% of Upk1b(RFP/RFP) mice possessed unilateral duplex kidneys. Our study expands the role of uroplakins, mechanistically links plaque formation to urinary tract development and function, and provides a tantalizing connection between congenital anomalies of the kidney and urinary tract along with functional deficits observed in a variety of urinary tract diseases. Thus, kidney and bladder urothelium are regionally distinct and remain highly plastic, capable of expansion through tissue-specific progenitor populations. Furthermore, Upk1b plays a previously unknown role in early kidney development representing a novel genetic target for congenital anomalies of the kidney and urinary tract.


Assuntos
Diferenciação Celular , Rim/metabolismo , Tetraspaninas/metabolismo , Bexiga Urinária/metabolismo , Urotélio/metabolismo , Animais , Proliferação de Células , Regulação da Expressão Gênica no Desenvolvimento , Genótipo , Homeostase , Hidronefrose/genética , Hidronefrose/metabolismo , Rim/anormalidades , Rim/ultraestrutura , Camundongos Knockout , Fenótipo , Transdução de Sinais , Tetraspaninas/deficiência , Tetraspaninas/genética , Bexiga Urinária/anormalidades , Bexiga Urinária/ultraestrutura , Anormalidades Urogenitais/genética , Anormalidades Urogenitais/metabolismo , Uroplaquina Ib , Urotélio/anormalidades , Urotélio/ultraestrutura , Refluxo Vesicoureteral/genética , Refluxo Vesicoureteral/metabolismo
17.
J Urol ; 193(2): 650-4, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25196655

RESUMO

PURPOSE: Bullying has become a social plague associated with various deleterious outcomes. We hypothesized that pediatric lower urinary tract symptoms could be associated with exposure to bullying. MATERIALS AND METHODS: We assessed exposure to school bullying via the Setting the Record Straight bullying questionnaire in children 8 to 11 years old being evaluated for lower urinary tract symptoms at our pediatric urology clinic. Lower urinary tract symptoms were quantified with the Vancouver Symptom Score. Children 8 to 11 years old presenting for pediatric well visits also completed the questionnaires. Linear regression assessed the relationship between Vancouver Symptom Score and bullying score. Categorical variables were compared by chi-square test, while continuous variables were compared using the Student t-test. RESULTS: A total of 113 children at the urology clinic and 63 children in the primary care setting consented to participate. There were significant differences between the 2 populations, including gender and race, with significantly more perpetrators of bullying in the primary care group (7.9% vs 0.9%, p = 0.02). When looking specifically at the urology group, there was a significant association between Vancouver Symptom Score and self-perceived (p <0.001) and peer perceived (p <0.001) victimization scores. In the primary care group there was also a significant association between Vancouver Symptom Score and self-perceived (p = 0.01) and peer perceived (p = 0.001) bullying perpetrator scores. Of children seen at the primary care office 33% had a significant Vancouver Symptom Score. CONCLUSIONS: Although bullying exposure is multifactorial, we found that Vancouver Symptom Score can be associated with bullying victimization and perpetrator scores.


Assuntos
Bullying , Sintomas do Trato Urinário Inferior/epidemiologia , Criança , Feminino , Humanos , Masculino , Pediatria , Instituições Acadêmicas , Inquéritos e Questionários , Urologia
18.
Int Braz J Urol ; 41(3): 562-8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26200552

RESUMO

PURPOSE: Literature pertaining to surgical disclosure to the pediatric patient is lacking. We hypothesized parents would find it difficult to disclose urologic surgery to a child. MATERIALS AND METHODS: Parents of patients <5 years old undergoing urologic surgery were contacted for telephone survey. Parents were asked about future plans of surgical disclosure, comfort with disclosure, and any support received. RESULTS: 98 parents consented to study participation. 87% of surgeries were on the genitalia with 62% being minor genitalia surgery (i.e. circumcision). 70% of parents would tell their child about minor genital surgery while 84% would tell about major genital surgery (p=0.07). 4 of 20 parents of children undergoing hypospadias repair (major genital surgery) did not plan to tell their child about surgery. All parents of children undergoing non-genital surgery would tell. Of all parents planning to tell their children about surgery, only 14% were nervous. 34% of parents would find guidance in talking to their child helpful despite the majority (90%) stating no guidance had ever been provided. CONCLUSIONS: Parents seem comfortable discussing urologic surgeries with a child but about 1/3 would appreciate further counseling. 20% of parents of children undergoing hypospadias repair hope to avoid telling their child.


Assuntos
Revelação/estatística & dados numéricos , Genitália/cirurgia , Relações Pais-Filho , Procedimentos Cirúrgicos Urológicos/psicologia , Adulto , Fatores Etários , Criança , Pré-Escolar , Tomada de Decisões , Feminino , Humanos , Entrevistas como Assunto , Masculino , Fatores Sexuais , Inquéritos e Questionários
19.
J Urol ; 191(2): 445-50, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23954583

RESUMO

PURPOSE: Ileovesicostomy is a reconstructive option in complex urological cases but pediatric specific outcomes are lacking. We report our results with pediatric ileovesicostomy. MATERIALS AND METHODS: We retrospectively evaluated patients younger than 18 years undergoing incontinent ileovesicostomy at Vanderbilt University. History, urinary tract management and operative course were reviewed in the electronic medical record. Particular attention was given to immediate and long-term postoperative complications. RESULTS: Nine patients underwent incontinent ileovesicostomy between 2000 and 2013 at a mean age of 10.3 years (range 1.4 to 15.5). Surgical indication was sequelae of neurogenic or nonneurogenic neurogenic bladder (such as infection or worsening hydronephrosis) in 5 patients, reversal of vesicostomy in 3 and closure of cloacal exstrophy in 1. All 9 patients were thought incapable of reliable clean intermittent catheterization due to family unwillingness, poor social support or patient refusal. Median followup was 11.5 months (mean 48.2, range 1.3 to 144.8). Immediate postoperative complications included ileus requiring total parenteral nutrition and a wound infection in 1 patient. Long-term complications included urinary tract infection in 2 patients (febrile in 1 and positive culture for foul smelling urine in 1), stomal issues in 2 and temporary urethral leakage in 1. Constipation affected 3 children in long-term followup (all with neurogenic bowel preoperatively). Postoperative creatinine was stable or improved in all patients. CONCLUSIONS: Ileovesicostomy is a viable approach in children left with few other options, particularly those who are noncompliant or physically/socially unable to handle catheterization. This operation can help keep such patients out of diapers.


Assuntos
Cistostomia/métodos , Ileostomia/métodos , Procedimentos de Cirurgia Plástica/métodos , Derivação Urinária/métodos , Incontinência Urinária/cirurgia , Adolescente , Criança , Pré-Escolar , Comorbidade , Feminino , Humanos , Lactente , Cateterismo Uretral Intermitente , Masculino , Meningomielocele/epidemiologia , Meningomielocele/fisiopatologia , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Resultado do Tratamento , Bexiga Urinaria Neurogênica/cirurgia , Incontinência Urinária/epidemiologia , Incontinência Urinária/fisiopatologia , Urodinâmica
20.
J Urol ; 191(5 Suppl): 1597-601, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24679873

RESUMO

PURPOSE: We theorized that progressive bladder dysfunction due to clinical diagnoses such as outlet obstruction occurs as a result of cyclical oxidative stress events. We hypothesized that measurement of F2-isoprostane, a marker of lipid peroxidation, could serve as a biomarker of oxidative stress in the murine bladder. MATERIALS AND METHODS: At age 5 to 6 weeks oophorectomized female mice were subjected to 1 of 2 bladder injury models, that is partial bladder outlet obstruction or acute bladder distension. The time points studied after injury included 4, 8 and 16 weeks after obstruction, and 0 to 48 hours after acute bladder distension. In a separate group short-term repetitive acute bladder distension was performed every other day for 14 days. Bladder samples were analyzed for F2-isoprostane using gas chromatography and mass spectroscopy. Mean tissue F2-isoprostane levels were compared. RESULTS: F2-isoprostane increased significantly after 4 weeks of partial bladder outlet obstruction from 1.46 ng/gm in controls to 2.31 ng/gm at 4 weeks (p = 0.01). Eight and 16 weeks after partial bladder outlet obstruction F2-isoprostane remained significantly elevated (2.39 and 2.48 ng/gm, respectively). Acute bladder distension resulted in a significant increase in F2-isoprostane immediately after distension compared to controls (1.6 vs 0.75 ng/gm, p = 0.04). In mice that underwent repetitive acute bladder distension F2-isoprostane did not change. CONCLUSIONS: Measurement of tissue F2-isoprostane in the bladder reflects the progression of oxidative stress, primarily in chronic injury models such as partial bladder outlet obstruction. The usefulness of F2-isoprostane measurements in shorter term injury models requires further study.


Assuntos
Biomarcadores/sangue , F2-Isoprostanos/sangue , Estresse Oxidativo/fisiologia , Obstrução do Colo da Bexiga Urinária/fisiopatologia , Envelhecimento/fisiologia , Animais , Modelos Animais de Doenças , Progressão da Doença , Feminino , Camundongos , Espécies Reativas de Oxigênio/sangue , Obstrução do Colo da Bexiga Urinária/sangue
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