The Relation of Soluble Klotho with Cardiovascular Disease, Chronic Kidney Disease Progression, and Blood Pressure in the Systolic Blood Pressure Intervention Trial

收缩压干预试验中可溶性 Klotho 与心血管疾病、慢性肾病进展和血压的关系

基本信息

  • 批准号:
    10451512
  • 负责人:
  • 金额:
    $ 29.89万
  • 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:
    2021-07-15 至 2026-04-30
  • 项目状态:
    未结题

项目摘要

ABSTRACT Soluble α-klotho (“Klotho”) has systemic effects in maintenance of cell health including reduction of oxidative stress and fibrosis in the heart and kidney. Kidney tubules are the primary source of circulating (soluble) klotho and therefore the development of chronic kidney disease (CKD) results in klotho deficiency. Klotho deficiency may also paradoxically contribute to CKD progression. Rodent models of klotho deficiency display vulnerability to kidney injury and progression of kidney disease, while administration of exogenous klotho attenuates kidney damage and disease progression. Klotho deficiency may also contribute to excess cardiovascular disease (CVD) risk in CKD as klotho knockout mice display vascular calcification and pathological cardiac remodeling with cardiac hypertrophy and fibrosis. Further, blood pressure (BP) may influence klotho levels as preclinical data show that multiple models of hypertension all result in klotho deficiency. Thus far, the majority of clinical studies examining soluble klotho have relied primarily on a single commercial source of ELISA. There are concerns about the performance and reproducibility of this assay as the clinical data have been inconsistent. Some studies have reported no relationship or higher levels of soluble klotho with reduced kidney function, while others have shown a parallel decline in klotho and kidney function. This discrepancy has hindered widespread measurement of klotho in large-scale human studies and has led to a paucity of quality data examining the role of klotho in human CKD. Similarly, there are no longitudinal data on changes in klotho over time in CKD. In a pilot project using samples from the Systolic Blood Pressure Intervention Trial (SPRINT) we compared the most widely used commercial ELISA with an immunoprecipitation-immunoblot (IP-IB) assay, and found that the IP-IB assay exhibited superior performance. Subsequently, we hope to address the current lack of high quality human studies examining soluble klotho as a risk factor for CVD and CKD progression. SPRINT is the ideal cohort to answer these questions as the trial enrolled 2646 participants with CKD and has detailed CVD and kidney outcomes. This cohort is also well-suited to examine the patient-specific and disease-specific clinical factors that may impact longitudinal changes in soluble klotho including: the intensive vs. standard blood pressure control intervention, measures of mineral metabolism including FGF-23, and measures of kidney tubular injury/health. We propose to measure baseline serum and urine klotho concentrations in 2646 SPRINT participants with CKD at baseline as well as in a pre-specified subset of 1000 persons at year 1 and year 4 to: 1) compare the IP-IB assay with the commercial klotho ELISA; 2) determine the association of klotho with CVD events, death, and CKD progression; and 3) identify the clinical factors that influence longitudinal changes in klotho including intensive vs. standard BP control, markers of mineral metabolism and/or kidney tubular health. Such data can collectively set the stage for future klotho interventional trials, inform clinical risk- stratification models and provide a foundation for translational research in klotho biology and therapeutics.
摘要

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)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

David Alan Drew其他文献

David Alan Drew的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('David Alan Drew', 18)}}的其他基金

The Relation of Soluble Klotho with Cardiovascular Disease, Chronic Kidney Disease Progression, and Blood Pressure in the Systolic Blood Pressure Intervention Trial
收缩压干预试验中可溶性 Klotho 与心血管疾病、慢性肾病进展和血压的关系
  • 批准号:
    10180234
  • 财政年份:
    2021
  • 资助金额:
    $ 29.89万
  • 项目类别:
The Relation of Soluble Klotho with Cardiovascular Disease, Chronic Kidney Disease Progression, and Blood Pressure in the Systolic Blood Pressure Intervention Trial
收缩压干预试验中可溶性 Klotho 与心血管疾病、慢性肾病进展和血压的关系
  • 批准号:
    10618989
  • 财政年份:
    2021
  • 资助金额:
    $ 29.89万
  • 项目类别:
The association of FGF-23 and Klotho with cognitive impairment and cerebrovascular disease in chronic kidney disease
FGF-23和Klotho与慢性肾脏病认知障碍和脑血管疾病的关系
  • 批准号:
    9304203
  • 财政年份:
    2016
  • 资助金额:
    $ 29.89万
  • 项目类别:
The association of FGF-23 and Klotho with cognitive impairment and cerebrovascular disease in chronic kidney disease
FGF-23和Klotho与慢性肾脏病认知障碍和脑血管疾病的关系
  • 批准号:
    9923642
  • 财政年份:
    2016
  • 资助金额:
    $ 29.89万
  • 项目类别:

相似海外基金

Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
  • 批准号:
    MR/S03398X/2
  • 财政年份:
    2024
  • 资助金额:
    $ 29.89万
  • 项目类别:
    Fellowship
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
  • 批准号:
    2338423
  • 财政年份:
    2024
  • 资助金额:
    $ 29.89万
  • 项目类别:
    Continuing Grant
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
  • 批准号:
    EP/Y001486/1
  • 财政年份:
    2024
  • 资助金额:
    $ 29.89万
  • 项目类别:
    Research Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
  • 批准号:
    MR/X03657X/1
  • 财政年份:
    2024
  • 资助金额:
    $ 29.89万
  • 项目类别:
    Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
  • 批准号:
    2348066
  • 财政年份:
    2024
  • 资助金额:
    $ 29.89万
  • 项目类别:
    Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
  • 批准号:
    AH/Z505481/1
  • 财政年份:
    2024
  • 资助金额:
    $ 29.89万
  • 项目类别:
    Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10107647
  • 财政年份:
    2024
  • 资助金额:
    $ 29.89万
  • 项目类别:
    EU-Funded
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
  • 批准号:
    2341402
  • 财政年份:
    2024
  • 资助金额:
    $ 29.89万
  • 项目类别:
    Standard Grant
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10106221
  • 财政年份:
    2024
  • 资助金额:
    $ 29.89万
  • 项目类别:
    EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
  • 批准号:
    AH/Z505341/1
  • 财政年份:
    2024
  • 资助金额:
    $ 29.89万
  • 项目类别:
    Research Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了