NIMBLE: Non-Invasive Markers of Bladder Deterioration
NIMBLE:膀胱恶化的非侵入性标志物
基本信息
- 批准号:10482352
- 负责人:
- 金额:$ 58.28万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-09-06 至 2026-06-30
- 项目状态:未结题
- 来源:
- 关键词:Anti-CholinergicsBiological MarkersBladderBladder TissueCatheterizationChildChronic Kidney FailureClinicalClinical ManagementComplementDetectionDeteriorationDevelopmentDysmyelopoietic SyndromesEvaluationGoldHumanInterobserver VariabilityInterventionKidneyLeadLongitudinal cohortLower urinary tractMass Spectrum AnalysisModelingMonitorNeurogenic BladderObstructionOperative Surgical ProceduresPathologicPatientsPharmaceutical PreparationsPharmacologyPopulationPrognostic MarkerProspective cohortProteinsProteomeProteomicsProtocols documentationRattusRenal functionRiskRodentSamplingSignal TransductionSpinal DysraphismTestingTimeTissuesUreteropelvic junction obstructionUrinary tractUrinary tract infectionUrineUrodynamicsbasebiomarker panelcohortimprovedinsightintravesicalpatient populationpostnatalprenatalpreservationpressureprospectiverenal damagerepairedresponsetertiary caretreatment responseurinaryurologic
项目摘要
Project Abstract
Neurogenic bladder from congenital myelodysplasia (Spina Bifida) presents lifelong challenges in bladder
management. Even with improved clinical management up to 50% of patients with SB are at increased risk for
development of chronic kidney disease associated with urologic complications of neurogenic bladder. Bladder
management for patients with neurogenic bladder comprises catheterization to promote emptying, medication to
decrease intravesical pressures and inhibit detrusor overactivity, and regular monitoring of bladder function by
urodynamics (UDS). If conservative therapy fails, patients may undergo surgical intervention to enhance capacity
and reduce intravesical pressure to minimize upper tract damage. Regardless, controversy exists over the best
management protocol for the neurogenic bladder. UDS is considered the gold standard for evaluation of lower
urinary tract function and the impetus for intervention. However, UDS is invasive, expensive, subject to
substantial inter-observer variability and not routinely available beyond tertiary care centers. The availability of a
quantitative, non-invasive approach to signal bladder changes that serve as a harbinger of renal deterioration
would advance clinical management of this patient population significantly. Notably, no such markers have been
validated prospectively as independent markers of functional bladder deterioration.
In preliminary studies, we have identified a panel of urine biomarkers enriched in urine from two models
of neurogenic bladder (human and rodent), but not detected in kidney urine from human patients with
ureteropelvic junction obstruction. This, together with their detection in bladder tissue from rats with neurogenic
bladder strongly suggests that this unique panel reflects pathological bladder wall remodeling as opposed to
renal damage. Based on these observations we hypothesize that our Non-Invasive Markers of Bladder
Deterioration (NIMBLE) represent prognostic markers of deterioration in bladder function in neurogenic
bladder patients. We believe that these markers may also serve as early predictors of upper tract damage in
this population. We will test the hypothesis with the following aims: Aim 1. Determine the association between
bladder-enriched urine biomarkers and functional parameters in a well characterized prospective cohort of
children with neurogenic bladder. Aim 2. Investigate bladder-enriched urine biomarkers, their association with
function and their response to treatment in a longitudinal cohort of children and rodents with neurogenic bladder.
In each aim we will use mass spectrometry-based proteomics to quantify our unique panel in sample cohorts
with neurogenic bladder, determine their association with functional UDS and their response to pharmacological
intervention. We will also profile the remaining urinary proteome to refine the biomarker panel. At the end of the
project we will know the extent to which our NIMBLE panel reflects functional deterioration of the neurogenic
bladder and how it could be implemented clinically to improve management of SB patients.
项目摘要
先天性脊髓发育不良(脊柱裂)引起的神经源性膀胱在膀胱治疗中面临终身挑战
管理即使临床管理得到改善,高达50%的SB患者的风险也会增加,
与神经源性膀胱的泌尿系统并发症相关的慢性肾脏疾病的发展。膀胱
神经源性膀胱患者的管理包括导管插入以促进排空,药物治疗,
降低膀胱内压,抑制逼尿肌过度活动,定期监测膀胱功能,
尿动力学(UDS)。如果保守治疗失败,患者可能会接受手术干预,以提高能力
并降低膀胱内压以使上尿路损伤最小化。无论如何,对于最好的,
神经源性膀胱的管理协议。UDS被认为是评估较低
尿路功能和干预的动力。然而,UDS是侵入性的,昂贵的,受
观察者之间的差异性很大,并且在三级护理中心之外无法常规获得。的可用性
一种定量、非侵入性的方法,用于信号膀胱变化,作为肾脏恶化的预兆
将大大推进这一患者群体的临床管理。值得注意的是,
作为功能性膀胱恶化的独立标志物。
在初步研究中,我们已经确定了一组尿液生物标志物富集在尿液中的两个模型
神经性膀胱(人类和啮齿动物),但未检测到人类患者的肾尿
肾盂输尿管连接部梗阻这一点,连同他们的检测膀胱组织从大鼠神经原性
膀胱强烈表明,这种独特的面板反映了病理性膀胱壁重塑,而不是
肾损伤基于这些观察结果,我们假设我们的非侵入性膀胱标记物
恶化(NIMBLE)代表神经源性膀胱功能恶化的预后标志物。
膀胱患者我们相信这些标记物也可以作为上尿路损伤的早期预测因子,
这个人口。我们将测试假设与以下目标:目标1.确定之间的关联
在一个充分表征的前瞻性队列中,
患有神经性膀胱的儿童。目标2.研究膀胱富集尿生物标志物,它们与
神经源性膀胱儿童和啮齿类动物纵向队列的功能及其对治疗的反应。
在每个目标中,我们将使用基于质谱的蛋白质组学来量化我们在样本队列中的独特面板
与神经源性膀胱,确定其与功能性UDS和他们的反应,药理学
干预我们还将对剩余的尿蛋白质组进行分析,以完善生物标志物组。结束时
项目,我们将知道我们的NIMBLE面板反映神经性功能恶化的程度。
膀胱以及如何在临床上实施,以改善SB患者的管理。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Rosalyn M Adam其他文献
CAVEOLIN-1 INTERACTS WITH A LIPID RAFT-ASSOCIATED POPULATION OF FATTY ACID SYNTHASE IN PROSTATE CANCER
- DOI:
10.1016/s0022-5347(08)61340-3 - 发表时间:
2008-04-01 - 期刊:
- 影响因子:
- 作者:
Dolores Di Vizio;Rosalyn M Adam;Jayoung Kim;Keith R Solomon;Robert Kim;Federica Sotgia;Michael P Lisanti;Massimo Loda;Mark A Rubin;Francesca Demichelis;Michael R Freeman - 通讯作者:
Michael R Freeman
HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN K IS A NOVEL REGULATOR OF ANDROGEN RECEPTOR TRANSLATION IN PROSTATE CANCER
- DOI:
10.1016/s0022-5347(08)60542-x - 发表时间:
2008-04-01 - 期刊:
- 影响因子:
- 作者:
Nishit Mukhopadhyay;Jayoung Kim;Bekir Cinar;Aruna Ramachandran;Martin Hager;Rosalyn M Adam;Pradip Raychaudhuri;Arrigo De Benedetti;Michael R Freeman - 通讯作者:
Michael R Freeman
STRUCTURAL CONFORMATION OF TYPE I COLLAGEN MATRICES MODULATES RETINOIC-ACID INDUCED SMOOTH MUSCLE CELL DIFFERENTIATION OF MOUSE EMBRYONIC STEM CELLS
- DOI:
10.1016/s0022-5347(08)60214-1 - 发表时间:
2008-04-01 - 期刊:
- 影响因子:
- 作者:
Joshua R Mauney;Rosalyn M Adam;George Q Daley;Carlos R Estrada - 通讯作者:
Carlos R Estrada
ENGINEERING BLADDER SMOOTH MUSCLE TISSUE: A NOVEL APPROACH USING 3-DIMENSIONAL SILK-BASED BIOMATERIALS AND PRIMARY HUMAN SMOOTH MUSCLE CELLS
- DOI:
10.1016/s0022-5347(08)60220-7 - 发表时间:
2008-04-01 - 期刊:
- 影响因子:
- 作者:
Joshua R Mauney;Rosalyn M Adam;Carlos R Estrada - 通讯作者:
Carlos R Estrada
UROEPITHELIAL DIFFERENTIATION OF MOUSE EMBRYONIC STEM CELLS USING NOVEL TISSUE CULTURE SYSTEMS
- DOI:
10.1016/s0022-5347(09)60123-3 - 发表时间:
2009-04-01 - 期刊:
- 影响因子:
- 作者:
Joshua R Mauney;Rosalyn M Adam;George Q Daley;Carlos R Estrada - 通讯作者:
Carlos R Estrada
Rosalyn M Adam的其他文献
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{{ truncateString('Rosalyn M Adam', 18)}}的其他基金
Precision-cut bladder slices: an enabling technology for urologic research
精密切割膀胱切片:泌尿学研究的支持技术
- 批准号:
10785220 - 财政年份:2023
- 资助金额:
$ 58.28万 - 项目类别:
NIMBLE: Non-Invasive Markers of Bladder Deterioration
NIMBLE:膀胱恶化的非侵入性标志物
- 批准号:
10316791 - 财政年份:2021
- 资助金额:
$ 58.28万 - 项目类别:
NIMBLE: Non-Invasive Markers of Bladder Deterioration
NIMBLE:膀胱恶化的非侵入性标志物
- 批准号:
10655624 - 财政年份:2021
- 资助金额:
$ 58.28万 - 项目类别:
The neuropilin 2 axis in smooth muscle contractility
平滑肌收缩力中的神经毡蛋白 2 轴
- 批准号:
9904119 - 财政年份:2016
- 资助金额:
$ 58.28万 - 项目类别:
The neuropilin 2 axis in smooth muscle contractility
平滑肌收缩力中的神经毡蛋白 2 轴
- 批准号:
9127579 - 财政年份:2016
- 资助金额:
$ 58.28万 - 项目类别:
The Environment-Gene Interface in Urologic Health and Disease
泌尿系统健康和疾病中的环境-基因界面
- 批准号:
9052367 - 财政年份:2015
- 资助金额:
$ 58.28万 - 项目类别:
Development of Novel Tools for Gene Targeting in Smooth Muscle
平滑肌基因靶向新工具的开发
- 批准号:
8328706 - 财政年份:2011
- 资助金额:
$ 58.28万 - 项目类别:
Development of Novel Tools for Gene Targeting in Smooth Muscle
平滑肌基因靶向新工具的开发
- 批准号:
8113766 - 财政年份:2011
- 资助金额:
$ 58.28万 - 项目类别:
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