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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：
10335132
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/10335132
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.

项目总结/摘要与NIH-NIDDK的目标一致，即“促进我们对性别差异的病理生理学的理解， CKD和改善女性CKD患者的临床护理”在2017年“性与肾脏：性肾脏疾病的差异”研讨会，该提案的重点是定义肾脏对妊娠的适应，识别妊娠并发症高危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，但我们对肾功能的认识仍存在重大差距。怀孕期间的适应。本提案的目标1A利用来自两个大型机构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中的标志物。初步数据显示肾小球超滤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未能正常妊娠的妇女胎盘发育的关键途径超滤研究超过3,000名怀孕受试者，这项工作将定义妊娠肾生理学，多样化的产科人群，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肾病妇女的先兆子痫。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，患有肾病的妇女中的先兆子痫。总之，了解肾适应的影响，妊娠前和妊娠期间的肾小球超滤将产生新的评估和治疗指标患有肾病的年轻女性计划怀孕。唐仁医生在美国完成了她的医学学位。宾夕法尼亚大学和她在布里格姆和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T. H.陈博士是公共卫生学院的教授，并在马萨诸塞州总医院担任教职医院肾脏科和哈佛医学院。在这次职业发展奖，她将投入75%的时间专注于这项研究计划，并完成教学和实践培训，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。博士Tangren将受益于她的主要导师Sushrut Waikar博士的指导，Sushrut Waikar博士是一位国际领先的 CKD流行病学和生物标志物研究，她的共同导师Ravi Thadhani博士，临床和翻译先兆子痫研究员她的培训将由一个由资深科学家组成的咨询委员会监督。 Ellen Seely、Lesley Inker和Jeffrey Ecker，在妊娠期代谢、肾小球疾病、过滤测量和产科研究。她将与尤金李博士（肾脏疾病代谢组学）和Sophia Zhao博士（生物统计学）。唐人医生的目标是成为一个独立的临床医生兼研究员，研究项目重点关注肾脏病学中的生殖健康。