Boston Chronic Kidney Disease Research Biopsy Center

项目摘要 慢性肾脏疾病（CKD）影响着3700万美国人，每年花费数百亿美元， 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 异质性疾病，具有广泛的潜在原因、病理和临床表现，以及 不同程度的肾功能丧失由于缺乏肾活检样本， CKD的常见形式和公认的动物模型的局限性，我们对病理学的理解， CKD的分子机制受到限制。提高对高血压所致人类CKD的认识， 糖尿病将需要研究CKD患者的肾组织，使用快速发展的技术， 分子病理学我们正在回应RFA-DK-20-026，以继续作为多中心CKD招募中心 肾脏精准医学项目（KPMP），该项目建立在我们建立的 UG 3/UH 3阶段的多学科研究小组。我们建议继续作为一个成功的 马萨诸塞州波士顿的CKD招募中心，包括四个临床中心：Joslin糖尿病中心、Beth Israel Deaconess 医学中心，布里格姆妇女医院和波士顿医学中心。该提案建立在 我们拥有完善的基础设施和丰富的招聘和留住KPMP参与者的经验。此外，我们的网站 具有出色的安全记录，参与者没有重大的活检后并发症， 生物样本质量指标。对于U 01期，我们建议在选定的患者中进行重复肾活检。 此外，还应加强对健康的社会决定因素的关注。我们还将继续进行活检 没有肾脏病理证据的长期1型糖尿病患者（“抵抗者”） 保护糖尿病肾病的分子基础。我们致力于继续 协作协议开发、共享最佳实践和团队科学，以实现KPMP的目标 推进精准医疗，以改善我们患有CKD和有CKD风险的患者的生活。拟议 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.