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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：
10256661
负责人：
Laura Malaga-Dieguez
金额：
$ 70.36万
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/10256661
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 Factors 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 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.

项目总结