Improving Scientific Rigor of Renal Clinical Endpoints for Sickle Cell Anemia

项目总结/摘要 母研究R 01将开发并验证新的eGFR方程，并测量GFR的变化 超过一年。患有镰状细胞性贫血（SCA）的个体患贫血的风险增加。 静脉血栓栓塞（VTE）的发展。这种风险可能会进一步增加， 进行性肾病的症状此外，血栓形成事件可能加速进展至终点- SCA患者肾脏疾病分期。前瞻性研究需要检查三个方向 SCA、慢性肾脏疾病和血栓事件之间的相关性。这项建议会 前瞻性检查200名儿童和200名成人SCA参与者的VTE患病率 基线时和1年时新发和复发性VTE的发生率。这些数据将提供 支持既往队列数据的前瞻性证据表明1年复发率为10-20% 对于首次发生血栓形成事件的SCA患者，接下来，该提案将 描述基线时继发性血栓形成的当前治疗方法， 一年时对二级血栓预防治疗的依从性。目前的ASH镰状细胞 由于缺乏可靠的证据，指南无法提供强有力的建议， 外地最后，该提案将测量参与者GFR变化的轨迹， 没有血栓病史探索性分析还将比较 在研究期间发生新血栓形成事件的受试者。这些数据对于确定 是否应将血栓形成事件史纳入肾脏结局分层 为今后研究肾保护剂在SCA。这些目标中的每一个都将提供至关重要的初步 数据支持在有以下病史的SCA患者中进行抗凝治疗的可行性试验： 血栓形成事件以及在VTE和持续血栓形成风险儿童中开展的更广泛试验 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.