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：
10659018
负责人：
Laura Malaga-Dieguez
金额：
$ 70.33万
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/10659018
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 Oxidative Stress Induction Pathogenesis Patients Perinatal Pesticides Pharmaceutical Preparations Phenotype Population Population Study Pre-Eclampsia Pregnancy Pregnant Women Prevention Process Productivity Proteinuria Renal Mass Renal function Renal glomerular disease Reporting Risk Risk Factors Role Sampling Serum Signal Transduction Testing Third Pregnancy Trimester Toddler Tubular formation Ultrasonography United States National Institutes of Health Universities Urine Urokinase Plasminogen Activator Receptor Work adverse childhood events 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 risk stratification 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.

项目概要纽约大学医学院、拉什大学医学中心和纽约州卫生部做出回应 PA-19-056，提议研究生命早期肾功能的发育起源和环境风险。慢性肾脏病 (CKD) 的发病率稳步上升，合成化学物质日益增多据了解，这会导致急性和慢性肾损伤。高患病人群的病例对照研究发病率已将杀虫剂和除草剂暴露视为风险，引发了一个问题：发育暴露可能更具影响力。我们自己对 CKD 儿童的研究 (R01DK100307) 研究表明，随着邻苯二甲酸盐和双酚暴露的增加，肾功能会适度下降，伴随着氧化应激的增加。然而，这些发现并不能帮助我们理解 CKD 的起源。一个主要的限制是我们和其他研究未能解释发育肾脏生物学和围产期/婴儿因素的强烈影响。本提案的前提是子宫内炎症过程会破坏肾发生，环境化学物质也会损害妊娠和产后发育期间肾实质通过氧化应激纵向生长。我们通过检查邻苯二甲酸盐、双酚、草甘膦和有机磷 (OP) 进一步质疑这一假设农药作为可改变的风险。我们将在纽约大学儿童健康中心测试这些假设环境研究，NIH 环境影响和儿童健康的参与群体之一结果计划 (UH3OD023305)。拟议的工作建立在我们在产后肾病方面的经验基础上超声测量，我们将前瞻性地将其添加到现有的、资助的随访中。方法是具有成本效益，利用针对妊娠期和婴儿期三类暴露类别的现有措施，可用生物样本来测量可溶性尿激酶型纤溶酶原激活剂受体，这是一种新兴的肾损伤和发育的标志物以及草甘膦。 MPI（Trasande 和 Trachtman）高度评价具有良好记录的儿童环境健康专家与肾脏病学专家互补、结合 R01DK100307 中富有成效的 MPI 伙伴关系，该伙伴关系产生了支持拟议的初步数据工作。分析将由纽约州沃兹沃斯实验室的 K. Kannan 进行健康博士，在精确测量尿液中的草甘膦和代谢物方面拥有丰富的经验。在与许多无法改变或避免的已知 CKD 风险相比，农药和通过食用有机食品可以减少除草剂，而通过以下方式可以减少邻苯二甲酸盐和双酚：避免罐头和加工食品。拟议的工作有可能改变起源的范式 CKD 需要将注意力集中在其发育起源上。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Changes in plasma soluble urokinase plasminogen activator receptor levels across pregnancy and in relation to hypertensive disorders.

怀孕期间血浆可溶性尿激酶纤溶酶原激活物受体水平的变化以及与高血压疾病的关系。

DOI：
发表时间：
2023-05
期刊：
影响因子：
0
作者：
Cowell, Whitney;Limaye, Meghana;Brukbaker, Sara G;Silverstein, Jenna S;Mehta;Kahn, Linda G;Malaga;Reiser, Jochen;Trasande, Leonardo
通讯作者：
Trasande, Leonardo

The NYU Children's Health and Environment Study.

纽约大学儿童健康与环境研究。

DOI：
发表时间：
2020-03
期刊：
影响因子：
13.6
作者：
Trasande, Leonardo;Ghassabian, Akhgar;Kahn, Linda G;Jacobson, Melanie H;Afanasyeva, Yelena;Liu, Mengling;Chen, Yu;Naidu, Mrudula;Alcedo, Garry;Gilbert, Joseph;Koshy, Tony T;NYU Children’s Health and Environment Study Team
通讯作者：
NYU Children’s Health and Environment Study Team

Effect of a gluten-free diet on albuminuria in children with newly diagnosed celiac disease.

无麸质饮食对新诊断乳糜泻儿童白蛋白尿的影响。