Biomarkers of Kidney Pathology

肾脏病理学的生物标志物

• 批准号: 8536281
• 负责人: Sushrut S. Waikar
• 金额: $ 61.2万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8536281
• 关键词: Acute; Address; Adult; Affect; Albuminuria; Ancillary Study; Animals; Atrophic; Biological; Biological Markers; Biopsy; Biopsy Specimen; Blinded; Blood; Blood Vessels; Blood capillaries; Boston; CCL2 gene; CXCL10 gene; Caring; Chronic; Chronic Kidney Failure; Clinical; Clinical Data; Cohort Studies; Collection; Creatinine; DNA; Data; Development; Diagnosis; Diagnostic; Discrimination; Disease; Drug or chemical Tissue Distribution; Early Diagnosis; Effectiveness; Enrollment; Etiology; Event; FABP1 gene; Fibrosis; Future; Glomerular Filtration Rate; Gold; Grant; Histologic; Histopathologic Grade; Histopathology; Home visitation; Hospitals; House Call; Immunohistochemistry; Individual; Inflammation; Inflammatory; Injury; Interleukin-18; Intervention; Israel; Kidney; Kidney Diseases; Lead; Lesion; Massachusetts; Measurement; Measures; Medical center; Methods; Morbidity - disease rate; Outcome; Participant; Pathologic Processes; Pathologist; Pathology; Patients; Performance; Plasma; Procedures; Process; Proportional Hazards Models; Public Health; Race; Renal Replacement Therapy; Renal function; Research Personnel; Risk; Risk Factors; Sampling; Sclerosis; Serum; Stratification; Structure of glomerular mesangium; Testing; Time; Tissues; Translating; Translations; Tubular formation; United States; Urine; Validation; Vascular Endothelial Growth Factors; Woman; adjudication; arteriole; base; capillary; clinical practice; cohort; connective tissue growth factor; follow-up; glomerulosclerosis; improved; indexing; mortality; novel; outcome forecast; prognostic; prospective; public health relevance; sample collection; statistics; tool; urinary

DESCRIPTION (provided by applicant): Chronic kidney disease affects approximately 26 to 30 million adults in the United States and is associated with substantial morbidity and mortality. The underlying causes of CKD and risk for progression in an individual patient are frequently not known in clinical practice. Nevertheless, several pathological processes appear to be common across progressive kidney diseases of diverse etiologies, including progressive tubulointerstitial fibrosis, tubular atrophy, glomerulosclerosis, capillary rarefaction, and vascular sclerosis. Novel non-invasive biomarkers of CKD pathology may provide clarification of the underlying pathobiological processes responsible for CKD in an individual, enabling earlier diagnosis and more accurate prognosis. This proposal is an ancillary study to the CKD Biomarker Consortium (U01DK085660), a group of investigators with wide-ranging biomarker expertise who have access to samples from a number of cohorts of individuals with CKD. The proposal describes a prospective cohort study involving biological sample collection from patients undergoing native kidney biopsy, the gold standard determination for identifying the cause(s) of CKD. We will enroll participants from two hospitals in Boston, Massachusetts and measure urinary and tissue levels of novel biomarkers, including KIM-1, NAG, NGAL, MCP-1, L-FABP, IL-18, HGF, VEGF, IP-10, and CTGF. In Specific Aim 1, we will correlate urinary biomarker measurements with 13 histologic scores that capture inflammatory, fibrotic, and ischemic pathological processes in the mesangium, tubules, glomeruli, interstitium, and arterioles; further immunohistochemistry will be performed on the most promising biomarkers to identify their tissue distribution and correlation with urinary levels. In Specific Aim 2, we will test the prospective associations of urinary and tissue biomarkers with renal function decline, defined as a doubling of serum creatinine or the need for renal replacement therapy. We anticipate enrollment of over 900 participants with median follow-up of approximately 5 years. This ancillary proposal will be collaborative and integrated with U01 Consortium investigators and will facilitate multidirectional translation of findings across animal studies, large cohort studies, and the biopsy cohort. Urine, plasma, and DNA samples will be shared with the Consortium for future studies.

描述（由申请人提供）：慢性肾脏疾病在美国影响约26至3000万成年人，并与大量发病率和死亡率有关。在临床实践中，经常不知道CKD的根本原因和在个别患者中进展的风险。然而，在各种病因的进行性肾脏疾病中，几个病理过程似乎很常见，包括进行性肾小管间质纤维化，肾小管萎缩，肾小球硬化症，毛细血管稀疏性和血管硬化症。小说 CKD病理学的非侵入性生物标志物可以澄清对个体中CKD的基本病理生物学过程，从而实现早期诊断和更准确的预后。该提案是对CKD生物标志物联盟（U01DK085660）的辅助研究，这是一组具有广泛生物标志物专业知识的研究人员，他们可以从许多CKD人群中获取样品。该提案描述了一项前瞻性队列研究，该研究涉及接受天然肾脏活检患者的生物样品收集，这是识别CKD原因的黄金标准测定。我们将入学来自马萨诸塞州波士顿的两家医院的参与者，并测量新型生物标志物的尿和组织水平，包括KIM-1，NAG，NGAL，MCP-1，MCP-1，L-FABP，IL-18，IL-18，HGF，HGF，VEGF，VEGF，IP-100和CTGF。在特定的目标1中，我们将将尿液生物标志物测量与13个组织学评分相关联，这些组织学评分捕获炎症，纤维化和缺血性病理过程中的肾小球，小管，肾小球，肾小球，间质和小动脉；将在最有希望的生物标志物上进行进一步的免疫组织化学，以鉴定其组织分布和与尿液水平的相关性。在特定目标2中，我们将测试尿液和组织生物标志物与肾功能下降的前瞻性关联，定义为血清肌酐的两倍或肾脏替代疗法的需求。我们预计中位随访大约5年的900多名参与者入学。该辅助提案将是协作的，并与U01联盟研究人员进行了整合，并将促进在动物研究，大型队列研究和活检队列中发现结果的多方向翻译。尿液，血浆和DNA样品将与财团共享以后的研究。