Environmental Oxidant Stressors in Pediatric Chronic Kidney Disease - Resubmissio

小儿慢性肾脏病中的环境氧化应激 - Resubmissio

• 批准号: 8911312
• 负责人: HOWARD TRACHTMAN
• 金额: $ 62.29万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-15 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8911312
• 关键词: Adolescent; Adult; Adverse effects; Affect; Albumins; Albuminuria; Ancillary Study; Animals; Area; Beverages; Biological; Biological Markers; Blood Pressure; Child; Child Care; Childhood; Childhood Injury; Chronic Kidney Failure; Clinical; Clinical Research; Clinical Trials; Cohort Studies; Collaborations; Comorbidity; Cross-Sectional Studies; Data; Diet; Diethylhexyl Phthalate; Disease; Disease Progression; End stage renal failure; Environmental Exposure; Environmental Health; Epidemiologic Studies; Esters; Etiology; Excretory function; Exposure to; Focal Segmental Glomerulosclerosis; Food; Food Processing; Funding; Gelatinase A; Glomerular Filtration Rate; Health; Human; Hypertension; Individual; Injury; Intervention; Kidney; Kidney Diseases; Link; Malondialdehyde; Medical; Microalbuminuria; Mission; Modification; Molecular Weight; National Health and Nutrition Examination Survey; National Institute of Diabetes and Digestive and Kidney Diseases; Nephrons; Nephrotic Syndrome; New York; Obesity; Outcome; Oxidants; Oxidative Stress; Patients; Performance; Plant Resins; Proteinuria; Randomized Clinical Trials; Relapse; Renal function; Renal glomerular disease; Reporting; Risk; Testing; Treatment Protocols; Tubular formation; Urogenital Abnormalities; Visit; Work; bisphenol A; cardiometabolic risk; cardiovascular disorder risk; cardiovascular risk factor; cost effective; environmental chemical; environmental chemical exposure; innovation; interest; macroalbuminuria; medical schools; novel; novel therapeutic intervention; oxidant stress; pediatric patients; phthalates; polycarbonate; prehypertension; prospective; rat KIM-1 protein; research study; response; stressor; successful intervention; therapy design; therapy resistant; urinary

DESCRIPTION (provided by applicant): In response to PA-12-265, "Ancillary Studies to Major Ongoing Clinical Research Studies to Advance Areas of Scientific Interest within the Mission of the NIDDK," NYU School of Medicine and the New York State Department of Health propose to assess the effect of exposure to environmental oxidant stressors, bisphenol A (BPA) and phthalates, in pediatric patients with chronic kidney disease (CKD). CKD can be caused by congenital abnormalities of the genitourinary tract or acquired glomerular disorders. Regardless of the underlying etiology, current treatment for CKD yields progress to end stage kidney disease. It is important disappointing outcomes and many affected children to identify modifiable factors that impact on the clinical course of CKD to design interventions can be adjuncts to medical therapy for affected children. BPA is used to manufacture polycarbonate resin that coat food and beverage containers, and phthalate metabolites are commonly found in processed foods. Both molecules cause oxidant stress, are associated with obesity and hypertension in children, and have been linked to increased risk of cardiovascular disease in adults. Preliminary data suggest that exposure to BPA and phthalates is associated with an increase in low-grade albuminuria in healthy children. However, the implications for these exposures in children who are more vulnerable because of medical conditions such as CKD has not been studied. We propose to test the hypothesis that exposure to BPA and phthalates will have an adverse effect in children with CKD and be associated with an increased risk of worse renal outcomes. This Ancillary Study will utilize stored biosamples that have been obtained during the performance of the following four NIDDK-funded clinical studies - CKiD, NEPTUNE, FSGS Clinical Trial and FONT trial. It will compare two groups of children with CKD - one with focal segmental glomerulosclerosis (FSGS) and a second with non-glomerular disease. The project will focus on children because of their unique vulnerability to environmental chemicals and reduced confounding by other co-morbidities that are prevalent in adults. We will assess longitudinal changes in kidney function assessed by estimated glomerular filtration rate (eGFR), proteinuria, blood pressure (BP), and excretion of biomarkers of tubular injury (KIM-1 and NGAL) associated with BPA and phthalate exposures in children with CKD. Finally, we will evaluate whether the environmental chemicals increase oxidant stress in children with CKD. This is the first study to assess the unique vulnerability of children with CKD to environmental exposures that are modifiable through diet and may provide rationale for newer therapeutic approaches to this group of patients. It unites a recognized pediatric nephrologist (H. Trachtman) with an expert in children's environmental health (L. Trasande), and builds upon a productive track record of collaboration between the multiple PIs.

描述（申请人提供）：作为对PA-12-265“在NIDDK的使命范围内推进科学兴趣领域的主要正在进行的临床研究的辅助研究”的回应，纽约大学医学院和纽约州卫生部建议评估暴露于环境氧化剂应激物、双酚A（BPA）和邻苯二甲酸盐的影响，儿童慢性肾病（CKD）患者。慢性肾脏病可由先天性泌尿生殖道异常或后天性肾小球疾病引起。无论潜在病因如何，目前CKD的治疗进展为终末期肾病。重要的是，令人失望的结果和许多受影响的儿童，以确定可改变的因素，影响CKD的临床过程中，设计干预措施，可以避免受影响的儿童的药物治疗。BPA用于制造涂覆食品和饮料容器的聚碳酸酯树脂，邻苯二甲酸酯代谢物通常存在于加工食品中。这两种分子都会引起氧化应激，与儿童肥胖和高血压有关，并与成人心血管疾病风险增加有关。初步数据表明，接触BPA和邻苯二甲酸酯与健康儿童低度白蛋白尿的增加有关。然而，尚未研究这些暴露对因CKD等医疗条件而更脆弱的儿童的影响。我们建议检验这一假设，即BPA和邻苯二甲酸酯暴露将对CKD儿童产生不良影响，并与肾脏结局恶化风险增加相关。本辅助研究将使用在以下四项NIDDK资助的临床研究（CKiD、NEPTUNE、FSGS临床试验和FONT试验）中获得的储存生物样本。它将比较两组CKD儿童-一组患有局灶节段性肾小球硬化症（FSGS），另一组患有非肾小球疾病。该项目将重点关注儿童，因为他们对环境化学品的独特脆弱性，以及减少成人中普遍存在的其他并发症的混淆。我们将通过估计的肾小球滤过率（eGFR）、蛋白尿、血压（BP）和与CKD儿童中BPA和邻苯二甲酸酯暴露相关的肾小管损伤生物标志物（KIM-1和NGAL）的排泄来评估肾功能的纵向变化。最后，我们将评估环境化学物质是否会增加CKD儿童的氧化应激。这是第一项评估CKD儿童对可通过饮食改变的环境暴露的独特脆弱性的研究，并可能为这组患者的新治疗方法提供依据。它联合了一位公认的儿科肾病学家（H。Trachtman）与儿童环境健康专家（L。Trasande），并建立在多个PI之间富有成效的协作记录之上。