Developmental Origins of Kidney Function in Early Life and Environmental Risks

生命早期肾功能的发育起源和环境风险

基本信息

批准号：
10064557
负责人：
HOWARD TRACHTMAN
金额：
$ 72.04万
依托单位：
NEW YORK UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-02 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10064557
关键词：
8-hydroxy-2&apos -deoxyguanosine Academic Medical Centers Actins Acute Adolescent Adoption Adult Age Age-Months Attention Biological Markers Birth Case-Control Studies Categories Cell membrane Chemicals Child Child Health Childhood Chronic Chronic Kidney Failure Complex Consumption Coupling Cytoskeleton Data Development Developmental Biology Environment Environmental Exposure Environmental Health Environmental Risk Factor Epidermal Growth Factor Exposure to F2-Isoprostanes Failure Fetal Growth Fetal Growth Retardation Food Funding Growth Health Herbicides ITGB3 gene Impairment Incidence Infant Inflammation Inflammatory Injury Injury to Kidney Interleukin-6 Kidney Laboratories Life Low Birth Weight Infant Measurement Measures Medical Modification Nephrology Nephrons New York Obesity Organic Food Organophosphates Outcome Oxidative Stress Pathogenesis Patients Perinatal Pesticides Pharmaceutical Preparations Phenotype Population Population Study Pre-Eclampsia Pregnancy Pregnant Women Prevention Process Proteinuria Renal Mass Renal function Renal glomerular disease Reporting Risk Risk stratification Role Sampling Serum Signal Transduction Testing Third Pregnancy Trimester Toddler Tubular formation United States National Institutes of Health Universities Urine Urokinase Plasminogen Activator Receptor Work adverse childhood events base cardiovascular risk factor cell motility cohort cost efficient cytokine diagnostic biomarker disorder risk early childhood environmental chemical experience follow-up glomerular filtration glyphosate in utero infancy medical schools modifiable risk nephrogenesis nephrotoxicity oxidant stress phthalates podocyte postnatal postnatal development premature prenatal prenatal exposure programs prospective rat KIM-1 protein specific biomarkers stressor trend urinary

项目摘要

Project Summary NYU School of Medicine, Rush University Medical Center and New York State Department of Health respond to PA-19-056, proposing to study developmental origins of kidney function in early life and environmental risks. The incidence of chronic kidney disease (CKD) is steadily rising and synthetic chemicals are increasingly understood to contribute to acute and chronic kidney injury. Case-control studies of populations with high incidence rates have identified pesticide and herbicide exposures as risks, raising the question whether developmental exposures may be even more impactful. Our own studies of children with CKD (R01DK100307) have revealed modest declines in kidney function with increasing phthalate and bisphenol exposures, accompanied by increases in oxidative stress. However, these findings do not contribute to our understanding of the origin of CKD. A major limitation is the failure of our and other studies to account for the developmental biology of the kidney and strong influence of perinatal/infant factors. The premise of the present proposal is that intrauterine inflammatory processes disrupt nephrogenesis and that environmental chemicals also impair renal parenchymal growth longitudinally during gestation and postnatal development via oxidant stress. We further interrogate this hypothesis by examining phthalates, bisphenols, glyphosate and organophosphate (OP) pesticides as modifiable risks. We will test these hypotheses in the New York University Children's Health and Environment Study, one of the participating cohorts in the NIH Environmental Influences and Child Health Outcomes Program (UH3OD023305). The proposed work builds upon our experience with postnatal renal sonographic measurement, which we will add prospectively to the existing, funded follow up. The approach is cost-efficient, leveraging existing measures for three exposure categories in pregnancy and infancy and available biospecimens to measure soluble urokinase-type plasminogen activator receptor, an emerging marker of kidney injury and development, and glyphosate. The MPIs (Trasande and Trachtman) are highly complementary, coupling experts in children's environmental health with nephrology who have a track record of productive MPI partnership in R01DK100307, which produced preliminary data in support of the proposed work. Analyses will be performed by K. Kannan at Wadsworth Laboratories of the New York State Department of Health, who has deep experience with precise measurement of glyphosate and metabolites in urine. In contrast to many known CKD risks which are not amenable to modification or avoidance, pesticides and herbicides can be reduced by consuming organic foods while phthalates and bisphenols can be reduced by avoiding canned and processed foods. The proposed work has the potential to shift the paradigm of origins of CKD to focus needed attention on its developmental origins.

项目摘要纽约大学医学院，拉什大学医学中心和纽约州卫生部响应到PA-19-056，提议研究早期生活和环境风险中肾脏功能的发育起源。慢性肾脏疾病（CKD）的发生率稳步上升，合成化学物质越来越多据了解会导致急性和慢性肾脏损伤。病例对照研究高发病率已经确定农药和除草剂的暴露是风险，提出了一个问题发展暴露可能更具影响力。我们对CKD儿童的研究（R01DK100307）揭示了肾脏功能的适度下降，邻苯二甲酸盐和双酚暴露量增加，伴随着氧化应激的增加。但是，这些发现并不有助于我们的理解 CKD的起源。一个主要限制是我们和其他研究未能解释发展肾脏的生物学和围产期/婴儿因素的强大影响。本提议的前提是宫内炎症过程破坏了肾病，环境化学物质也损害了肾实质生长在妊娠和产后发育过程中通过氧化剂应激进行纵向生长。我们通过检查邻苯二甲酸，双苯酚，草甘膦和有机磷酸盐（OP）来进一步询问这一假设。农药是可修改的风险。我们将在纽约大学儿童健康中检验这些假设环境研究，NIH环境影响和儿童健康的参与人群之一结果程序（UH3OD023305）。拟议的工作以我们在产后肾脏的经验为基础超声测量，我们将前瞻性地添加到现有的资助后续行动中。方法是成本效益，利用怀孕和婴儿期三个暴露类别的现有措施，可用的生物测量来测量可溶性尿激酶型纤溶酶原激活剂受体，一种出现的肾脏损伤和发育的标记以及草甘膦。 MPI（Trasande和Trachtman）很高具有往绩记录的儿童环境健康的互补，耦合专家 R01DK100307的生产MPI合作伙伴关系，该合作生成了初步数据以支持拟议的工作。分析将由纽约州沃兹沃思实验室的K. Kannan进行健康，他在尿液中精确测量草甘膦和代谢物方面具有深厚的经验。在与许多已知的CKD风险形成对比，这些风险不适合修改或避免，农药和除草剂可以通过食用有机食品而减少，而邻苯二甲酸盐和双酚可以通过避免罐头和加工食品。拟议的工作有可能改变 CKD要集中精力需要关注其发展起源。