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（由申请人提供）：响应 PA-12-265，“对主要正在进行的临床研究的辅助研究，以推进 NIDDK 使命内的科学兴趣领域”、纽约大学医学院和纽约州卫生部门健康部门建议评估暴露于环境氧化剂应激源、双酚 A (BPA) 和邻苯二甲酸盐对患有慢性肾病 (CKD) 的儿科患者的影响。 CKD 可由先天性泌尿生殖道异常或后天性肾小球疾病引起。无论潜在的病因如何，目前对 CKD 的治疗都会导致终末期肾病。重要的是令人失望的结果，许多受影响的儿童需要确定影响 CKD 临床病程的可改变因素，以设计干预措施，以辅助受影响儿童的药物治疗。 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常见于加工食品中。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 和邻苯二甲酸盐与健康儿童低度蛋白尿的增加有关。然而，尚未研究这些暴露对因 CKD 等疾病而更容易受到伤害的儿童的影响。我们建议检验以下假设：接触 BPA 和邻苯二甲酸盐会对 CKD 儿童产生不利影响，并与肾脏结局恶化的风险增加相关。该辅助研究将利用在执行以下四项 NIDDK 资助的临床研究（CKiD、NEPTUNE、FSGS 临床试验和 FONT 试验）期间获得的存储生物样本。它将比较两组患有 CKD 的儿童——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物质的独特脆弱性，并且减少了成人中常见的其他合并症的混淆。我们将通过估计肾小球滤过率 (eGFR)、蛋白尿、血压 (BP) 以及与 CKD 儿童 BPA 和邻苯二甲酸盐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 儿童对环境暴露的独特脆弱性的研究，这些脆弱性可通过饮食改变，并可能为针对此类患者的新治疗方法提供依据。它由一位公认的儿科肾病专家 (H. Trachtman) 和一位儿童环境健康专家 (L. Trasande) 联合起来，并建立在多个 PI 之间富有成效的合作记录的基础上。