Boston Chronic Kidney Disease Research Biopsy Center

项目总结 慢性肾脏疾病(CKD)影响着3700万美国人，每年造成数百亿美元的损失，而且 导致肾衰竭、心血管疾病(CVD)和早期死亡。CKD不是一个单一的实体，而是一个 具有广泛的潜在原因、病理和临床表现的异质性疾病，以及 肾功能损失率各不相同。由于缺乏来自慢性肾炎患者的肾活检样本 慢性肾脏病的常见形式和动物模型公认的局限性以及我们对其病理学的理解 CKD的分子机制有限。提高对人类高血压和慢性肾脏病的认识 糖尿病将需要对慢性肾脏病患者的肾脏组织进行研究，使用快速发展的技术 分子病理学。我们正在响应RFA-DK-20-026，继续作为一个多中心CKD招聘网站 为肾脏精准医学项目(KPMP)建立在我们现有成就的基础上 UG3/UH3阶段的多学科研究小组。我们建议继续作为一个成功的 位于马萨诸塞州波士顿的CKD招聘网站包括四个临床网站：Joslin糖尿病中心，Beth以色列女执事 医疗中心、布里格姆妇女医院和波士顿医疗中心。这项提议建立在一个 已建立的基础设施和我们招募和留住KPMP参与者的经验。此外，我们的网站 有出色的参与者安全记录，没有重大的活组织检查后并发症以及超过 生物样品的质量指标。对于U01期，我们建议在选定的患者中进行重复的肾脏活检 此外，还应加强对健康的社会决定因素的关注。我们还将继续做活组织检查 长期患有1型糖尿病但无肾脏病理证据的个体(抵抗者)以确定 预防糖尿病肾病的分子基础。我们致力于继续 协作性协议开发、共享最佳实践和团队科学以实现KPMP的目标 发展精准医学以改善CKD患者和有CKD风险的患者的生活。建议数 研究计划，通过提高我们对CKD病理生理学的理解，有可能极大地影响 公共卫生。

PROJECT SUMMARY Chronic kidney disease (CKD) affects 37 million Americans, costs tens of billions of dollars annually, and can lead to kidney failure, cardiovascular disease (CVD), and early mortality. CKD is not a single entity but rather a heterogeneous condition with a wide spectrum of underlying causes, pathologic and clinical manifestations, and varying rates of loss of kidney function. Because of the paucity of kidney biopsy samples from patients with common forms of CKD and the acknowledged limitations of animal models, our understanding of the pathology and molecular mechanisms of CKD is limited. Improved understanding of human CKD due to hypertension and diabetes will require investigation of kidney tissue from patients with CKD, using rapidly evolving techniques in molecular pathology. We are responding to RFA-DK-20-026 to continue as a multicenter CKD recruitment site for the Kidney Precision Medicine Project (KPMP) that builds upon the accomplishments of our established multidisciplinary research group in the UG3/UH3 phase. We propose to continue to participate as a successful CKD recruitment site in Boston, MA including four clinical sites: Joslin Diabetes Center, Beth Israel Deaconess Medical Center, Brigham and Women’s Hospital, and Boston Medical Center. The proposal builds upon an established infrastructure and our experience recruiting and retaining KPMP participants. In addition, our site has an outstanding safety record for participants with no major post-biopsy complications as well as exceeding the quality biospecimen metrics. For the U01 phase we propose to obtain repeat kidney biopsies in selected individuals as well as increase the focus on social determinants of health. We also will continue to biopsy individuals with longstanding Type 1 diabetes mellitus with no evidence of kidney pathology (‘resistors') to identify molecular underpinnings of protection against diabetic kidney disease. We are committed to continued collaborative protocol development, sharing best practices, and team science to achieve the KPMP’s objectives of advancing precision medicine to improve the lives of our patients with and at risk for CKD. The proposed research plan, by improving our understanding of CKD pathophysiology, has the potential to dramatically impact public health.