Harvard Chronic Kidney Disease Research Biopsy Center

哈佛慢性肾脏病研究活检中心

• 批准号: 9394445
• 负责人: Sylvia E Rosas
• 金额: $ 37.94万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-18 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9394445
• 关键词: Address; Adult; Affect; Albuminuria; Animal Model; Archives; Atlases; Autopsy; Biological Markers; Biopsy; Biopsy Specimen; Blood Glucose; Boston; Cardiovascular Diseases; Chronic Kidney Failure; Clinical; Communities; Complications of Diabetes Mellitus; Consent; DNA; Data; Diabetes Mellitus; Diabetic Nephropathy; Diagnosis; End stage renal failure; Enrollment; Ethicists; Ethics; Fibrosis; Focal Segmental Glomerulosclerosis; Freezing; Functional disorder; General Hospitals; Glomerular Filtration Rate; Hospitals; Human; Hypertension; Individual; Institution; Insulin-Dependent Diabetes Mellitus; Investigation; Israel; Kidney; Kidney Failure; Lead; Longitudinal Studies; Maps; Massachusetts; Medical center; Membranous Glomerulonephritis; Microvascular Dysfunction; Molecular; Nephrectomy; Non-Insulin-Dependent Diabetes Mellitus; Paraffin; Paraffin Embedding; Participant; Pathologic; Pathology; Patient Recruitments; Patients; Phase; Phenotype; Pilot Projects; Plasma; Population; Probability Samples; Proteinuria; Proteome; Protocols documentation; Public Health; RNA; Recruitment Activity; Research; Research Infrastructure; Research Personnel; Research Project Grants; Resistance; Rest; Risk; Safety; Sampling; Science; Site; Spatial Distribution; Specimen; Survivors; Techniques; Tissue Embedding; Tissue Sample; Tissues; Training; Urine; Woman; biobank; cohort; cost; diabetic; improved; insight; interstitial; kidney cell; meetings; metabolome; molecular pathology; mortality; multidisciplinary; non-diabetic; precision medicine; prospective; protocol development; sample collection; transcriptome

PROJECT SUMMARY Chronic kidney disease (CKD) affects >10% of the adult US population, costs tens of billions of dollars annually, and can lead to progressive 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 rates of progression. 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. Deeper understanding of human CKD will require investigation of kidney tissue from patients with CKD, using rapidly evolving techniques in molecular pathology. In this proposal we have established a multidisciplinary investigative team and outline plans for a multicenter CKD recruitment site for the Kidney Precision Medicine Project (KPMP) [RFA-DK-16-026] involving Brigham and Women’s Hospital, Joslin Diabetes Center, Beth Israel Deaconess Medical Center, and Massachusetts General Hospital. The proposal builds upon an established infrastructure, the Boston Kidney Biopsy Consortium (BKBC, R01DK093574) that has successfully enrolled, collected biospecimens, and longitudinally followed > 800 patients undergoing native kidney biopsy at the four institutions. We will share plasma, urine, DNA, RNA, and archival kidney tissue specimens from the BKBC with the KPMP in order to accelerate progress in the UG3 phase and beyond. We will also share samples from U01DK104308, a study that collects intraoperative kidney tissue samples from non-cancer cortex during nephrectomy for research in kidney fibrosis. For the UG3 phase we propose participating in collaborative discussions to define the scientific objectives and to address the ethics and safety of kidney biopsy in CKD. Pilot studies in the UG3 phase will include research biopsies in patients with CKD who do not typically undergo kidney biopsy, and research cores from patients undergoing clinically indicated biopsies for CKD. In the UH3 phase, we propose expanding the study to include larger numbers of research biopsies across different stages of CKD. We also propose biopsies in individuals with longstanding Type 1 diabetes mellitus with no evidence of kidney pathology, in order to identify molecular underpinnings of protection against diabetic kidney disease. We also outline a proposal for repeat biopsies in 10 participants with rapid annual loss of estimated GFR (>5 ml/min/year) and in 10 participants with no change in estimated GFR (<1ml/min/year). We are committed to 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.

项目概要 慢性肾病 (CKD) 影响超过 10% 的美国成年人口，造成数百亿美元的损失 每年都会发生这种情况，并可能导致进行性肾衰竭、心血管疾病 (CVD) 和早期死亡。慢性肾病是 不是一个单一的实体，而是具有广泛潜在原因的异质状况，病理学 以及临床表现和进展率。由于肾活检样本很少 患有常见形式 CKD 的患者以及动物模型的公认局限性，我们对 CKD 的病理学和分子机制有限。更深入地了解人类 CKD 需要 使用快速发展的分子病理学技术对 CKD 患者的肾组织进行研究。 在这项提案中，我们建立了一个多学科调查小组，并概述了多中心的计划 涉及 Brigham 的肾脏精准医学项目 (KPMP) [RFA-DK-16-026] 的 CKD 招募网站 和妇女医院、乔斯林糖尿病中心、贝斯以色列女执事医疗中心和马萨诸塞州 综合医院。该提案建立在现有的基础设施之上，即波士顿肾活检 已成功登记、收集生物样本并进行纵向研究的联盟（BKBC，R01DK093574） 对 800 多名在这四个机构接受肾活检的患者进行了随访。我们将分享血浆、尿液、 与 KPMP 一起从 BKBC 获取 DNA、RNA 和档案肾组织样本，以加速 UG3 阶段及以后的进展。我们还将分享 U01DK104308 的样本，该研究收集了 肾切除术期间取自非癌皮层的术中肾组织样本，用于肾脏研究 纤维化。对于 UG3 阶段，我们建议参与协作讨论来定义科学 目标并解决 CKD 肾活检的伦理和安全问题。 UG3 阶段的试点研究将 包括对通常不接受肾活检的 CKD 患者进行研究活检，以及研究核心 来自接受临床指示的 CKD 活检的患者。在UH3阶段，我们建议扩大 研究纳入了 CKD 不同阶段的大量研究活检。我们还建议进行活检 对于长期患有 1 型糖尿病但没有肾脏病理证据的个体，为了 确定预防糖尿病肾病的分子基础。我们还概述了一项提案 对 10 名每年估计 GFR 快速下降（> 5 毫升/分钟/年）的参与者和 10 名参与者重复进行活检 估计 GFR 没有变化的参与者（<1ml/分钟/年）。我们致力于协作协议 发展、分享最佳实践和团队科学，以实现 KPMP 的推进目标 精准医疗旨在改善 CKD 患者和面临 CKD 风险的患者的生活。拟议的研究计划， 通过提高我们对 CKD 病理生理学的了解，有可能极大地影响公众健康。