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

项目摘要/摘要 慢性肾脏疾病非常普遍(≈占人口的15%)，费用高昂(≈每年为10亿美元)， 与高死亡率(每千人年109.7人)有关。已知的风险因素，如糖尿病，只能解释 慢性肾脏病风险差异的一部分。为了帮助预防慢性肾脏病，迫切需要研究确定新的风险因素 与早期肾小球滤过率(GFR)下降和发生CKD有关。一个很有前途的领域是心理健康 精神错乱。据报道，抑郁症与肾小球滤过率下降和慢性肾脏病有关。相比之下，没有研究表明 调查了创伤后应激障碍(创伤后应激障碍)，这是世界旅游中心响应者的常见精神病学诊断(≈10- 20%)，与肾脏疾病有关。对2266名受试者进行的初步研究显示，创伤后应激障碍的发病率为1.74倍 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)提供 创伤后应激障碍/慢性肾脏病关联的新证据。更多的研究表明，严重的创伤后应激障碍和创伤后应激障碍并存 抑郁与肾小球滤过率下降有较强的相关性，提示存在剂量-反应关系。 这项研究的目标是检验创伤后应激障碍的严重程度/病程可以预测 罹患慢性肾脏病的风险。这项研究还将检验肾脏疾病和创伤后应激障碍共享遗传/蛋白质生物标记物的假设。 使用所有可用的WTC Responder数据，在更长的随访期内从10,000名患者那里获得数据，并研究 创伤后应激障碍、药物和合并症的纵向变化与肾小球滤过率变化的关系，这项研究将 建立创伤后应激障碍和突发事件CKD之间的关联。这些数据将被用来开发风险预测模型。 使用PTSD和CKD的多基因风险评分和存储的蛋白质组数据，这项研究将识别基因/蛋白质变异 与创伤后应激障碍和CKD/GFR下降的共同途径有关。 这项研究提案将解决目前该领域的一个空白，有助于理解如何 慢性精神压力会导致WTC应答者的肾脏疾病，并将导致对以下影响的进一步研究 肾脏的精神创伤。利用已确定的重要临床、实验室和遗传/蛋白质风险因素，这款R21 该项目将导致开发复杂的CKD风险预测模型，用于在未来研究中进行测试 未来R01/UO1。结果可能导致临床医生通过基因组学/蛋白质组学和创伤后应激障碍严重程度对患者进行风险分层 并为未来对慢性精神压力患者的临床试验提供信息。这位候选人坚定地致力于在 翻译肾病研究，有扎实的个人基础(耶鲁大学博士学位)和临床培训背景 并得到了他的机构领导以及联合国环境规划署主任和首席研究员的大力支持 石溪世贸中心健康计划。这位候选人已经组建了一个由合作调查员和顾问组成的多样化团队 所有拟议研究计划的领域，并在其机构拥有完成拟议研究所需的所有资源 在分配的时间和预算中。

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.