Investigating the association of posttraumatic stress disorder (PTSD) with chronic kidney disease (CKD) in World Trade Center (WTC) responders

项目概要/摘要 慢性肾脏疾病（CKD）非常普遍（约占人口的15%），成本高昂（每年640亿美元）， 与高死亡率（109.7/1000患者-年）相关。已知的风险因素，如糖尿病，只能解释 CKD风险差异的一部分。为了帮助预防CKD，迫切需要进行研究以确定新的风险因素 与肾小球滤过率（GFR）早期下降和CKD事件相关。一个有希望的领域是心理健康 紊乱据报道，抑郁症与GFR下降和CKD相关。相比之下，没有任何研究 调查是否创伤后应激障碍（PTSD），一种常见的精神病诊断在世贸中心反应（2010年- 20%），与肾脏疾病有关。在2,266名受试者中进行的WTC初步研究显示，PTSD有1.74倍的 与GFR下降的相关性更高（与稳定的GFR相比，在调整所有主要CKD风险因素后）， PTSD/CKD相关性的新证据。进一步的研究表明，严重的创伤后应激障碍和创伤后应激障碍与共病 抑郁症与GFR下降有较强的相关性，表明存在剂量反应关系。 本研究的目的是检验创伤后应激障碍的严重程度/病程可以预测 CKD的风险这项研究还将测试肾脏疾病和PTSD共享遗传/蛋白质生物标志物的假设。 使用来自> 10，000名患者的所有可用的WTC应答者数据，在较长的随访期内， PTSD的纵向变化、药物和共病状况与GFR变化的相关性，本研究将 建立创伤后应激障碍和慢性肾病之间的联系。这些数据将用于开发风险预测模型。 使用PTSD和CKD的多基因风险评分和存储的蛋白质组学数据，本研究将识别基因/蛋白质变体 与PTSD和CKD/GFR下降之间的共同途径有关。 这项研究提案将通过帮助了解如何解决该领域目前的差距， 慢性精神压力会导致WTC反应者的肾脏疾病，并将导致进一步研究 肾脏受到精神创伤使用确定的重要临床、实验室和遗传/蛋白质风险因素， 该项目将开发复杂的慢性肾脏病风险预测模型，用于在前瞻性研究中进行测试 未来的R 01/UO 1。结果可能导致临床医生通过基因组学/蛋白质组学和PTSD严重程度对患者进行风险分层 并为未来针对慢性精神压力患者的临床试验提供信息。候选人坚定地致力于 翻译肾脏学研究，在基础（耶鲁大学博士）和临床方面都有坚实的个人背景 科学，并得到他的机构领导和主任和首席研究员的大力支持， 斯托尼布鲁克世贸中心健康计划。候选人组建了一个由合作调查员和顾问组成的多元化团队， 拟议研究计划的所有领域，并在其机构拥有完成拟议研究所需的所有资源 在预算和时间内。

Project Summary/Abstract Chronic kidney disease (CKD) is highly prevalent (≈15% of the population), costly (≈ $ 64 billion yearly) and associated with a high mortality rate (109.7 per 1,000 patient-years). Known risk factors, such as diabetes, explain only part of the variance in risk for CKD. To help prevent CKD, research is urgently needed to identify novel risk factors associated with early decline in glomerular filtration rate (GFR) and incident CKD. A promising area is mental health disorders. Depression has been reported to be associated with GFR decline and CKD. In contrast, no research has investigated whether post-traumatic stress disorder (PTSD), a common psychiatric diagnosis in WTC responders (≈10- 20%), is associated with kidney disease. Preliminary studies of WTC in 2,266 subjects revealed that PTSD had a 1.74 fold higher association with GFR decline (compared to stable GFR, after adjustment of all major CKD risk factors) providing novel evidence for the PTSD/CKD association. Additional studies revealed that severe PTSD and PTSD with co-morbid depression that a stronger association with GFR decline suggesting a dose-response relationship. The objectives of this research proposal are to test the hypotheses that severity/course of PTSD can predict the risk of CKD. This study will also test the hypothesis that kidney disease and PTSD share genetic/protein biomarkers. Using all available WTC Responder data from > 10,000 patients over a longer follow-up period and studying the association of longitudinal changes in PTSD, medications and co-morbid conditions with changes in GFR, this study will establish the association between PTSD and incident CKD. This data will be used to develop risk prediction models. Using polygenic risk scores for PTSD and CKD and stored proteomic data, this study will identify gene/protein variants related to common pathways between PTSD and CKD/GFR decline. This research proposal will address a current gap in the field by contributing to the understanding of how chronic mental stress contributes to kidney disease in the WTC responders and will lead to further studies on the effects of mental trauma on the kidneys. Using the significant clinical, laboratory and genetic/protein risk factors identified, this R21 project will lead to the development of sophisticated CKD risk prediction models for testing in prospective studies in a future R01/UO1. Results could lead to clinicians risk stratifying patients through genomics/proteomics and PTSD severity and inform future clinical trials of patients with chronic mental stress. The candidate is firmly committed to a career in translational nephrology research, has a solid personal background of training in both basic (PhD from Yale) and clinical science and is very strongly supported by his institutional leadership and by the Director and Principal Investigator of the Stony Brook WTC Wellness Program. The candidate has assembled a diverse team of co-investigators and consultants in all areas of the proposed research plan and has all the required resources at his institution to complete the proposed studies in allocated time and budget.