Advancing acute kidney injury phenotyping using biological and clinical criteria
使用生物学和临床标准推进急性肾损伤表型分析
基本信息
- 批准号:9926251
- 负责人:
- 金额:$ 17.78万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-07-01 至 2022-05-31
- 项目状态:已结题
- 来源:
- 关键词:Accident and Emergency departmentAcute Renal Failure with Renal Papillary NecrosisAdultAdult Respiratory Distress SyndromeAffectAwardBiologicalBiological MarkersBiologyCaliforniaCardiac Surgery proceduresCardiovascular systemChildChronic Kidney FailureClinicalClinical DataClinical TrialsComplexCreatinineCritical CareCritical IllnessDataData AnalysesData CollectionDevelopmentDiseaseDisease ProgressionDoctor of PhilosophyEnrollmentEpidemiologyFellowshipFibrinolysisFluid BalanceFluid overloadFundingGoalsHospitalsInfectionInflammationInjuryInjury to KidneyIntensive Care UnitsKidneyLung TransplantationMeasurementMedical StudentsMedicineMentorsMentorshipMethodsMorbidity - disease rateOutcomePathogenesisPatient-Focused OutcomesPatientsPhenotypePlasmaPopulation HeterogeneityPositive-Pressure RespirationPrincipal InvestigatorRandomizedRandomized Clinical TrialsRenal functionResearchResearch PersonnelRoleSamplingSan FranciscoSepsisSerumSpecialistSubgroupSupportive careSyndromeTestingTimeTrainingTranslational ResearchTransplant RecipientsTubular formationUnited States National Institutes of HealthUniversitiesUrineWorkbiomarker identificationcareerclinical practicecohortdesignimprovedimproved outcomelung injurymid-career facultymortalitymortality risknovelnovel markerpatient orientedpatient oriented researchpatient populationprogramsskills
项目摘要
PROJECT ABSTRACT
This is a new K24 application for Kathleen D. Liu, MD, PhD, MAS, who is an Associate Professor of
Medicine at the University of California, San Francisco where she is a nephrologist and critical care medicine
specialist with a strong record of mentoring medical students, residents and fellows who want to train for a
career in academic medicine. In the 10 years since completing her fellowship, she has established a well-
funded independent research program focused primarily on acute kidney injury (AKI), a common disease of
hospitalized patients for which no therapies apart from supportive care exist. One of Dr. Liu's long term goals is
to conduct randomized clinical trials that will improve the care of critically ill patients with AKI. Sepsis is the
leading cause of AKI in the Intensive Care Unit (ICU). A major criticism of failed sepsis clinical trials has been
that the patient population is likely too heterogeneous to benefit. Thus, the overall theme of the research
proposed in this K24 application is to refine phenotyping of sepsis-associated AKI. For these studies, she
will extend her research by leveraging the Early Assessment of Renal and Lung Injury (EARLI) cohort, a NIH-
supported cohort of ICU patients admitted from the Emergency Department at 2 UCSF-affiliated hospitals.
In Aim 1, Dr. Liu will test the impact of fluid overload on AKI ascertainment in patients with sepsis. Serum
creatinine (sCr), which is used to define AKI, is affected by volume of distribution (e.g., sCr is lower in patients
with fluid overload). Among patients with the acute respiratory distress syndrome (ARDS), Dr. Liu has shown
that fluid overload impacts AKI ascertainment. Further research is now needed to better understand the impact
of fluid overload on AKI ascertainment in patients with sepsis, and on the relationship of biomarkers with the
development of AKI. In Aim 2, she will use “clinically agnostic”, or unbiased methods, that may allow for
identification of AKI sub-phenotypes. Latent class analysis has been applied to ARDS to identify sub-
phenotypes using clinical and biological data. When sub-phenotypes of AKI are identified, these can be used
to (1) further define the biology of these sub-phenotypes and (2) test potential therapies in a sub-phenotype
that is more likely to benefit. Thus Aim 2 will use latent class analysis methods to incorporate biological and
clinical criteria to identify more homogenous patient groups with AKI.
This proposal will support additional biomarker measurements using banked samples and further clinical
data collection in the EARLI cohort to provide a platform for mentoring new investigators in patient-oriented
translational research. Additionally, as detailed in the Specific Aims, through this proposal Dr. Liu will acquire
new skills in latent class analysis which will enable her to test this approach in other patient cohorts and will
enhance her role as mentor to junior investigators in patient-oriented translational research. Finally, this award
will provide Dr. Liu with critical protected time to further develop her mentorship skills and to devote to
mentoring trainees committed to careers in patient-oriented research.
项目摘要
这是凯思琳·D·刘的新K24申请,她是麻省理工学院副教授,医学博士,MAS
她是加州大学旧金山分校的肾病学家和重症监护医学专家
具有指导医学生、住院医生和研究员的良好记录的专家,他们希望为
在学术医学方面的职业。在完成奖学金后的10年里,她建立了一个很好的-
资助的独立研究项目主要集中在急性肾损伤(AKI),这是一种常见的
除了支持性护理外没有其他治疗方法的住院患者。刘博士的长期目标之一是
进行随机临床试验,以改善AKI危重患者的护理。脓毒症是
重症监护病房(ICU)AKI的主要原因。对败血症临床试验失败的主要批评是
患者群体可能太过多样化而无法受益。因此,研究的总主题是
在这项K24应用中提出的是完善败血症相关AKI的表型。在这些研究中,她
将通过利用肾和肺损伤早期评估(EARLI)队列来扩展她的研究,这是一家NIH-
支持从加州大学旧金山分校附属医院的急诊科住院的ICU患者队列。
在目标1中,刘博士将测试液体超载对脓毒症患者AKI确定的影响。血清
用来定义AKI的肌酐(Scr)受分布体积的影响(例如,患者的Scr较低
体液过载)。在患有急性呼吸窘迫综合征(ARDS)的患者中,刘博士展示了
流体超载影响了AKI的确定。现在需要进一步的研究来更好地了解影响
脓毒症患者液体超负荷对AKI测定的影响以及生物标志物与
AKI的发展。在目标2中,她将使用“临床不可知论”或无偏见的方法,这可能允许
AKI亚型的鉴定。潜在类分析已被应用于ARDS,以识别子
使用临床和生物学数据进行表型分析。当确定AKI的亚表型时,可以使用这些
以(1)进一步确定这些亚型的生物学和(2)在亚型中测试潜在的治疗方法
这更有可能受益。因此,目标2将使用潜在类分析方法来结合生物学和
临床标准,以确定更多同质性的AKI患者组。
这项提议将支持使用储存的样本进行额外的生物标记物测量,并进一步用于临床
在EARLI队列中收集数据,为指导新的以患者为导向的研究人员提供平台
翻译研究。此外,根据具体目标的详细说明,通过这项提案,刘博士将获得
潜在类别分析的新技能,这将使她能够在其他患者队列和意愿中测试这种方法
在面向患者的翻译研究中,加强她作为初级调查人员的导师的角色。最后,这个奖项
将为刘博士提供关键的保护时间,以进一步发展她的指导技能并致力于
指导受训人员致力于以患者为中心的研究。
项目成果
期刊论文数量(0)
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Kathleen D Liu其他文献
Kathleen D Liu的其他文献
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{{ truncateString('Kathleen D Liu', 18)}}的其他基金
Advancing acute kidney injury phenotyping using biological and clinical criteria
使用生物学和临床标准推进急性肾损伤表型分析
- 批准号:
10163159 - 财政年份:2017
- 资助金额:
$ 17.78万 - 项目类别:
Acute Kidney Injury: A Novel Risk Factor for Cardiovascular Events
急性肾损伤:心血管事件的新危险因素
- 批准号:
8906848 - 财政年份:2014
- 资助金额:
$ 17.78万 - 项目类别:
Acute Kidney Injury: A Novel Risk Factor for Cardiovascular Events
急性肾损伤:心血管事件的新危险因素
- 批准号:
8759177 - 财政年份:2014
- 资助金额:
$ 17.78万 - 项目类别:
Role of Par3/Par6/aPKC Complex in Cell Polarity
Par3/Par6/aPKC 复合物在细胞极性中的作用
- 批准号:
6836108 - 财政年份:2004
- 资助金额:
$ 17.78万 - 项目类别: