Renal Circulatory Adaptation in Healthy and Complicated Pregnancies

项目摘要/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 慢性肾脏病与改善女性慢性肾脏病的临床护理在2017年《性与肾脏：性》中概述 肾脏疾病的差异“研讨会，这项建议侧重于定义肾脏对怀孕和 确定慢性肾脏病孕妇妊娠并发症高危人群的策略。越来越多的证据表明 肾功能与先兆子痫之间有很强的联系，但我们对肾脏的认识仍然存在重大差距 孕期适应。该提案的目标1A利用了来自两个大公司的现有数据和血液样本 前瞻性纵向妊娠队列研究与妊娠相关的肾小球滤过变化 健康和复杂妊娠的标志物。初步数据显示肾小球高滤过受损 与胎盘功能障碍有关，在Aim 1B中，我们将研究代谢物和血管生成 与正常妊娠相关的女性胎盘发育的关键途径 超滤。研究了3000多名孕妇，这项工作将在一个 不同的产科人群，并确定将肾功能和胎儿胎盘发育联系起来的途径 可能有针对性地减少患有肾脏疾病的妇女的先兆子痫。在目标2中，我们将进行测量和研究 孕前肾功能储备作为妊娠相关肾小球滤过的预测因子 肾病妇女的先兆子痫。共同理解肾脏适应的影响和 妊娠前和孕期肾小球高滤过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。唐仁博士在哈佛大学完成了她的医学学位 宾夕法尼亚大学和她在布里格姆和女子医院接受的内科和肾脏病培训 医院和马萨诸塞州综合医院。她最近在哈佛大学完成了公共卫生硕士学位 哈佛大学公共卫生学院，在马萨诸塞州总医院担任教职 医院肾病科和哈佛医学院。在这个职业发展奖期间，她将 她将75%的时间集中在这项研究计划上，并在 通过课程学习和应用分析经验进行生理研究和代谢途径分析。 唐格伦博士将受益于她的主要导师Sushrut Waikar博士的指导，他是 CKD流行病学和生物标记物研究，以及她的共同导师Ravi Thadhani博士，临床和翻译 先兆子痫调查员。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，在妊娠代谢，肾小球 过滤测量和产科研究。她将与尤金·李博士(肾脏)合作 疾病代谢学)和索菲亚·赵博士(生物统计学)。唐仁博士的目标是成为一名独立的 临床医生-研究员，有一项专注于肾脏病生殖健康的研究计划。

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.