Improving Scientific Rigor of Renal Clinical Endpoints for Sickle Cell Anemia

项目摘要/摘要 母公司R01将开发和验证新的EGFR方程并测量GFR的变化 一年多了。患有镰状细胞性贫血(SCA)的人患上 发生静脉血栓栓塞症(VTE)。这种风险可能会在环境中进一步增加 进行性肾脏疾病。此外，血栓事件可能会加速进展到结束- 个人肾脏疾病分期：SCA。需要进行前瞻性研究，以检查三个方向 SCA、慢性肾脏疾病和血栓事件之间的关系。这项提议将 前瞻性研究200例儿童和200例成人SCA患者的VTE患病率 基线和一年内新发和复发的静脉血栓栓塞率。这些数据将提供 支持先前队列数据的预期证据表明一年复发率为10%-20% 对于那些首次发生血栓事件的SCA患者的VTE。下一步，这项提议将 描述当前继发性血栓形成的治疗方法 坚持二次血栓预防治疗一年。当前的ASH镰刀电池 由于缺乏确凿的证据，指南无法提供强有力的建议 田野。最后，该提案将测量参与者的GFR变化轨迹和 没有血栓病史。探索性分析还将比较 在研究期间有新的血栓事件的参与者。这些数据对于确定 是否应将血栓事件史包括在肾脏结局的分层中 用于SCA中肾脏保护剂的未来研究。这些目标中的每一个都将提供至关重要的初步 数据支持在有SCA病史的患者中进行抗凝治疗的可行性试验 静脉血栓栓塞症和持续血栓形成风险儿童的血栓事件以及更广泛的试验 各种因素。

Project Summary/Abstract The parent R01 will develop and validate a novel eGFR equation and measure changes in GFR over one year. Individuals with sickle cell anemia (SCA) are at an increased risk for the development of venous thromboembolism (VTE). This risk likely increases further in the setting of progressive kidney disease. In addition, thrombotic events may hasten the progression to end- stage renal disease in individuals SCA. Prospective studies are need to examine the tri-directional associations between SCA, chronic kidney disease, and thrombotic events. This proposal will prospectively examine the prevalence of VTE in 200 pediatric and 200 adult participants with SCA at baseline and the incidence of new and recurrent VTE at one year. This data will provide prospective evidence to support prior cohort data suggesting a 10-20% one-year recurrence rate for VTE in those with SCA who have had a first thrombotic event. Next, this proposal will characterize the current treatment approaches to secondary thrombosis at baseline and adherence to secondary thromboprophylaxis treatment at one year. The current ASH Sickle Cell Guidelines were unable to provide strong recommendations due to the lack of solid evidence in the field. Finally, the proposal will measure the trajectory of GFR changes in participants with and without a history of thrombosis. Exploratory analysis will also compare the trajectory for participants with a new thrombotic event during the study period. This data is vital to determine whether a history of thrombotic events should be included in the stratification of renal outcomes for future studies of renoprotective agents in SCA. Each of these aims will provide vital preliminary data to support a feasibility trial of anticoagulation in individuals with SCA who have a history of thrombotic events as well as broader trials in children with VTE and persistent thrombotic risk factors.