Kids: Nocturnal Investigation into Glomerular Disease, Hypertension, and Transcriptomics (kNIGHT)
儿童:肾小球疾病、高血压和转录组学的夜间调查 (kNIGHT)
基本信息
- 批准号:10583680
- 负责人:
- 金额:$ 74.68万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-03-15 至 2028-02-29
- 项目状态:未结题
- 来源:
- 关键词:AdultAgeAmbulatory Blood Pressure MonitoringAmerican Heart AssociationAtherosclerosisBioinformaticsBlood PressureCardiacCardiovascular DiseasesCardiovascular systemChildChild HealthChronic Kidney FailureClinical DataClinical MarkersDataDevelopmentDiseaseDisease MarkerDisease OutcomeDyslipidemiasEchocardiographyEnrollmentFunctional disorderFundingFutureGene ExpressionGenesGenomicsGoalsGuide preventionHealthHigh PrevalenceHomeHourHydrocortisoneHypertensionInflammationIntakeInvestigationKidneyKnowledgeLaboratoriesLeftLeft Ventricular DysfunctionLeft Ventricular HypertrophyLeft Ventricular MassLinkLipidsLongitudinal StudiesLongitudinal, observational studyMachine LearningMeasurementMeasuresMetabolicMethodologyMolecularMorbidity - disease rateMultiomic DataNephrotic SyndromeNocturnal HypertensionOrganOutcomePathologicPathway interactionsPatientsPatternPhenotypePhysical activityPhysiologic pulsePopulationPreventionProteomicsQuestionnairesRare DiseasesRenal glomerular diseaseResearchRiskRisk FactorsRisk MarkerRisk ReductionSalivarySleepSleep Apnea SyndromesSodiumSystems BiologyTimeUnited States National Institutes of HealthValidationVentricularWhole BloodWorkactigraphyarterial stiffnesscardiovascular disorder riskcardiovascular healthcardiovascular risk factorcircadianclinical predictorscohortdata integrationdesigndifferential expressionexperiencefatty acid metabolismhigh riskhigh risk populationimprovedindexinginnovationmachine learning methodmetabolomicsmolecular markermortalitynovelobservational cohort studypatient orientedprecision medicinepredictive markerpredictive modelingrandomized, clinical trialssleep qualitytranscriptometranscriptomics
项目摘要
PROJECT SUMMARY/ABSTRACT
Children with proteinuric glomerulopathies are at considerable risk for cardiovascular disease. In addition to the
high prevalence of traditional cardiovascular disease risk factors in this population, more than half of children
with proteinuric glomerulopathies experience nocturnal blood pressure dysregulation, defined by nocturnal
hypertension or a reduced decline in nocturnal blood pressure (non-dipping pattern). Nocturnal blood pressure
dysregulation is independently associated with poor cardiovascular disease outcomes in adults. In this context,
the objective of this proposal is to understand the cardiovascular disease risks, clinical predictors and molecular
markers associated with nocturnal blood pressure dysregulation in children with proteinuric glomerulopathies.
The central hypothesis is that nocturnal blood pressure dysregulation is independently associated with
progression of cardiovascular target organ damage over time in children with proteinuric glomerulopathies. It is
further hypothesized that clinical and molecular markers will be associated with the nocturnal blood pressure
dysregulation phenotype. The specific aims of this proposal are: (Aim 1) To determine how nocturnal blood
pressure dysregulation associates with target organ damage over time in children with proteinuric
glomerulopathies; (Aim 2) To identify sleep- and circadian-related predictors of nocturnal blood pressure
dysregulation in children with proteinuric glomerulopathies; (Aim 3) To investigate molecular pathways, networks
and metabolic alterations associated with nocturnal blood pressure dysregulation in children with proteinuric
glomerulopathies using multi-omic data integration
. The proposed study will investigate nocturnal blood pressure
dysregulation in a multi-center, longitudinal observational study of 120 children with proteinuric glomerulopathies
enrolled from the Nephrotic Syndrome Study Network (NEPTUNE) and Cure Glomerulonephropathy Network
(CureGN). Cardiovascular measures will be followed for three years to determine how the nocturnal BP
dysregulation phenotype associates with progression of cardiovascular target organ damage. Predictive models
will then be developed using machine learning methods to identify the clinical predictors of nocturnal blood
pressure dysregulation, with a particular emphasis on sleep- and circadian-related predictors. Further, a
precision medicine approach will be employed to define molecular markers of nocturnal blood pressure
dysregulation using multi-omic data (genomics, transcriptomics, proteomics, metabolomics) integration. To this
end, identifying the health risks, clinical predictors and molecular markers associated with nocturnal blood
pressure dysregulation among children with proteinuric glomerulopathies using innovative bioinformatics
approaches to analyze existing and novel data will fill a significant knowledge gap for a population of children at
great cardiovascular risk. This study will ultimately guide prevention and treatment to meaningfully improve
cardiovascular disease outcomes in these children with proteinuric glomerulopathies.
项目总结/摘要
患有蛋白尿性肾小球病的儿童患心血管疾病的风险相当大。除了有
在这一人群中,传统心血管疾病危险因素的患病率较高,超过一半的儿童
患有蛋白尿性肾小球病的患者经历夜间血压失调,
高血压或夜间血压下降减少(非下降模式)。夜间血压
在成人中,失调与不良心血管疾病结局独立相关。在这一背景下,
本提案的目的是了解心血管疾病的风险、临床预测因素和分子水平
与蛋白尿性肾小球病儿童夜间血压失调相关的标志物
中心假设是,夜间血压失调是独立相关的,
蛋白尿性肾小球病患儿心血管靶器官损害随时间的进展是
进一步假设临床和分子标记物与夜间血压相关
失调表型本提案的具体目的是:(目的1)确定夜间血液
蛋白尿患儿血压失调与靶器官损害相关
肾小球疾病;(目的2)确定睡眠和昼夜节律相关的夜间血压预测因子
蛋白尿性肾小球疾病患儿的调节异常;(目的3)研究蛋白尿性肾小球疾病的分子通路、网络
蛋白尿儿童夜间血压失调相关的代谢改变
使用多组学数据集成的肾小球病
.这项研究将调查夜间血压
一项对120名蛋白尿性肾小球病儿童进行的多中心纵向观察性研究中的调节异常
从肾病综合症研究网络(NEPTUNE)和治愈肾小球肾病网络招募
(CureGN)。心血管测量将随访三年,以确定夜间BP
失调表型与心血管靶器官损伤的进展相关。预测模型
然后将使用机器学习方法开发,以确定夜间血液的临床预测因素。
压力失调,特别强调睡眠和昼夜节律相关的预测因素。此外,A
将采用精确医学方法来确定夜间血压的分子标志物
使用多组学数据(基因组学、转录组学、蛋白质组学、代谢组学)整合的失调。本
最后,确定与夜间血液相关的健康风险、临床预测因子和分子标志物,
利用创新生物信息学研究蛋白尿性肾小球病患儿的压力失调
分析现有和新数据的方法将填补儿童人口的重大知识空白,
心血管风险很大。这项研究将最终指导预防和治疗,以有意义地改善
这些患有蛋白尿性肾小球病的儿童的心血管疾病结局。
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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Christine B Sethna其他文献
Christine B Sethna的其他文献
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{{ truncateString('Christine B Sethna', 18)}}的其他基金
A Pilot Study of Transcutaneous Auricular Vagus Nerve Stimulation for the Treatment of Idiopathic Nephrotic Syndrome in Children
经皮耳迷走神经刺激治疗儿童特发性肾病综合征的初步研究
- 批准号:
10516390 - 财政年份:2022
- 资助金额:
$ 74.68万 - 项目类别:
A Pilot Study of Transcutaneous Auricular Vagus Nerve Stimulation for the Treatment of Idiopathic Nephrotic Syndrome in Children
经皮耳迷走神经刺激治疗儿童特发性肾病综合征的初步研究
- 批准号:
10684191 - 财政年份:2022
- 资助金额:
$ 74.68万 - 项目类别:
REDUCTION OF NOCTURNAL HYPERTENSION IN PEDIATRIC RENAL TRANSPLANT RECIPIENTS
减少儿童肾移植受者的夜间高血压
- 批准号:
8167277 - 财政年份:2010
- 资助金额:
$ 74.68万 - 项目类别:
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