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Renal Circulatory Adaptation in Healthy and Complicated Pregnancies

健康和复杂妊娠中的肾循环适应

基本信息

批准号：
10090592
负责人：
JESSICA Sheehan Tangren
金额：
$ 17.26万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-04-02 至 2024-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10090592
关键词：
Acute Acute Renal Failure with Renal Papillary Necrosis Advisory Committees Affect African American Age Amino Acid Metabolism Pathway Animal Model Appointment Biochemical Biological Markers Biometry Blood specimen Caring Caucasians Chronic Kidney Failure Clinical Clinical Trials Collaborations Conceptions Critical Pathways Data Delayed Childbearing Development Discipline of obstetrics Educational workshop Enrollment Epidemiology Ethics Faculty Failure Fatty Acids Fetal Growth Retardation Filtration First Pregnancy Trimester Foundations Functional disorder General Hospitals Glomerular Filtration Rate Goals High-Risk Pregnancy Hospitals Human Impairment Internal Medicine International Investigation Iothalamate K-Series Research Career Programs Kidney Kidney Diseases Knowledge Lead Link Literature Massachusetts Maternal Mortality Measurement Measures Medical Mentors Mentorship Metabolic Pathway Metabolism Methods Modernization Morbidity - disease rate National Institute of Diabetes and Digestive and Kidney Diseases Nephrology Obesity PGF gene Pathologic Pathway Analysis Pathway interactions Pennsylvania Physiological Physiology Placentation Planned Pregnancy Population Pre-Eclampsia Pregnancy Pregnancy Complications Pregnant Women Prevalence Prevention Proteins Public Health Public Health Schools Recording of previous events Renal Circulation Renal Mass Renal function Reporting Reproductive Health Research Research Personnel Risk Risk Factors Sampling Scientist Second Pregnancy Trimester Senior Scientist Sex Differences Stimulus Subgroup Testing Third Pregnancy Trimester Time Training United States United States National Institutes of Health Universities Vascular Endothelial Growth Factor Receptor-1 Woman Women&apos s Health Work career clinical care cohort experience fetal functional loss glomerular filtration healthy pregnancy high risk population improved insight kidney dysfunction maternal morbidity medical schools metabolomics novel offspring pregnant prognostic programs prospective protein metabolite reproductive response sex stressor therapeutic target trend trying to conceive urinary young woman

项目摘要

PROJECT SUMMARY/ABSTRACT Aligning with the NIH-NIDDK goal of “advancing our understanding of the pathophysiology of sex differences in CKD and improving clinical care of women with CKD” outlined at the 2017 “Sex and the Kidney: Sex Differences in Renal Disease” workshop, this proposal focuses on defining renal adaptation to pregnancy and strategies to identify women with CKD at high risk for pregnancy complications. Growing evidence suggests a strong link between kidney function and preeclampsia, yet significant gaps persist in our knowledge of renal adaptation in pregnancy. Aim 1A of this proposal utilizes existing data and blood samples from two large prospective longitudinal pregnancy cohorts to study pregnancy-associated changes in glomerular filtration markers in healthy and complicated pregnancies. Preliminary data suggests impaired glomerular hyperfiltration is associated with placental dysfunction, and in Aim 1B we will investigate metabolite and angiogenic pathways critical for placental development in women who fail to mount normal pregnancy-associated hyperfiltration. Studying over 3,000 pregnant subjects, this work will define gestational renal physiology in a diverse obstetric population and identify pathways linking kidney function and fetoplacental development that may be targeted to reduce preeclampsia in women with kidney disease. In Aim 2, we will measure and study pre-conception renal functional reserve as a predictor of pregnancy-associated glomerular filtration and preeclampsia in women with kidney disease. Together, understanding the effects of renal adaptation and glomerular hyperfiltration before and during pregnancy will yield new metrics by which to evaluate and treat young women with kidney disease planning pregnancy. Dr. Tangren completed her medical degree at the University of Pennsylvania and her internal medicine and nephrology training at Brigham and Women’s Hospital and Massachusetts General Hospital. She recently completed a Master’s in Public Health at the Harvard T.H. Chan School of Public Health and holds a faculty appointment in the Massachusetts General Hospital Nephrology Division and Harvard Medical School. During this career development award, she will devote 75% of her time to focus on this research plan and complete didactic and hands-on training in physiologic investigation and metabolic pathway analysis through coursework and applied analytic experience. Dr. Tangren will benefit from the guidance of her primary mentor, Dr. Sushrut Waikar, an international leader in CKD epidemiology and biomarkers studies, and her co-mentor Dr. Ravi Thadhani, a clinical and translational preeclampsia investigator. Her training will be overseen by an advisory committee of senior scientists, Drs. Ellen Seely, Lesley Inker, and Jeffrey Ecker, with collective expertise in metabolism in pregnancy, glomerular filtration measurements and obstetrics research. She will work in collaboration with Dr. Eugene Rhee (kidney disease metabolomics) and Dr. Sophia Zhao (biostatistics). Dr. Tangren’s goal is to become an independent clinician-investigator with a research program focused on reproductive health in nephrology.

项目概要/摘要与 NIH-NIDDK 的目标一致，即“增进我们对性别差异病理生理学的理解” CKD 和改善 CKD 女性患者的临床护理”在 2017 年“性与肾脏：性”会议上概述肾脏疾病的差异”研讨会，该提案的重点是定义肾脏对怀孕和妊娠的适应识别妊娠并发症高风险 CKD 女性的策略。越来越多的证据表明肾功能与先兆子痫之间存在密切联系，但我们对肾功能的了解仍然存在显着差距怀孕期间的适应。该提案的目标 1A 利用来自两个大型企业的现有数据和血液样本前瞻性纵向妊娠队列研究妊娠相关的肾小球滤过变化健康和复杂妊娠的标志物。初步数据表明肾小球过度滤过受损与胎盘功能障碍有关，在目标 1B 中，我们将研究代谢物和血管生成对于未能正常妊娠的女性，胎盘发育至关重要的途径超滤。这项工作研究了 3,000 多名怀孕受试者，将在一定程度上定义妊娠肾脏生理学不同的产科人群，并确定连接肾功能和胎儿胎盘发育的途径可能有针对性地减少患有肾脏疾病的女性的先兆子痫。在目标 2 中，我们将测量和研究孕前肾功能储备作为妊娠相关肾小球滤过的预测因子患有肾脏疾病的女性患有先兆子痫。一起了解肾脏适应的影响和怀孕前和怀孕期间的肾小球过度滤过将产生新的指标来评估和治疗患有肾脏疾病的年轻女性计划怀孕。唐仁博士在该大学完成了医学学位宾夕法尼亚大学和她在布莱根妇女医院接受的内科和肾脏病学培训医院和马萨诸塞州总医院。她最近完成了公共卫生硕士学位哈佛大学 T.H.陈公共卫生学院并在马萨诸塞州综合医院担任教职医院肾脏科和哈佛医学院。在此职业发展奖期间，她将投入 75% 的时间专注于这项研究计划并完成以下方面的教学和实践培训通过课程作业和应用分析经验进行生理调查和代谢途径分析。 Tangren 博士将受益于她的主要导师 Sushrut Waikar 博士的指导，Sushrut Waikar 博士是医学领域的国际领袖。 CKD 流行病学和生物标志物研究，以及她的共同导师 Ravi Thadhani 博士（一位临床和转化专家）先兆子痫研究者。她的培训将由资深科学家顾问委员会监督。 Ellen Seely、Lesley Inker 和 Jeffrey Ecker 在妊娠、肾小球代谢方面拥有集体专业知识过滤测量和产科研究。她将与 Eugene Rhee 博士（肾脏疾病代谢组学）和 Sophia Zhu 博士（生物统计学）。唐人博士的目标是成为一名独立的人临床医生兼研究员，其研究项目专注于肾脏病学生殖健康。