Urine galectin-3 as a biomarker of cardio-renal phenotype and prognosis

尿液半乳糖凝集素 3 作为心肾表型和预后的生物标志物

• 批准号: 9762206
• 负责人: Veena Rao
• 金额: $ 12.56万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-10 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9762206
• 关键词: Address; Aldosterone Antagonists; Animals; Attenuated; Biological; Biological Markers; Biopsy; Blood; Cessation of life; Cirrhosis; Clinical; Collagen; Connective Tissue; Contusions; Data; Data Set; Deposition; Development; Disease; EFRAC; Fibrosis; Filtration; Functional disorder; Galectin 3; Glomerular Filtration Rate; Goals; Gold; Heart; Heart Transplantation; Heart failure; Human; Infection; Injury; Intervention; Investments; Kidney; Kidney Diseases; Kidney Failure; LCN2 gene; Literature; Measures; Mediator of activation protein; Methods; Natriuretic Peptides; Organ; Outcome; Pain; Pathologic; Pathology; Pathway interactions; Patients; Phenotype; Physiology; Placebos; Plasma; Population; Procollagen Type III; Production; Publishing; Pulmonary Fibrosis; Randomized; Renal Tissue; Reporting; Research; Research Project Grants; Research Support; Resources; Risk; Role; Sampling Errors; Severities; Specimen; Spironolactone; Subgroup; Systemic disease; Tissues; Tubular formation; Urine; adverse event risk; attenuation; biobank; biomarker evaluation; clinical care; clinical decision-making; clinically relevant; cohort; coronary fibrosis; cost; data warehouse; experience; heart function; heart preservation; high risk; improved; interest; interstitial; kidney biopsy; kidney dysfunction; kidney fibrosis; mortality risk; outcome forecast; patient population; patient stratification; preservation; procollagen Type III-N-terminal peptide; prognostic; prognostic value; stem; tool; urinary

The identification of reliable metrics to assess renal fibrosis, the final common pathway for progressive renal disease, is of paramount importance. Currently the gold standard method for determining renal fibrosis is obtaining tissue by biopsy. Unfortunately, renal biopsy is by definition invasive, associated with complications such as pain, bruising, infection and even death. As a result of the risk profile, cost and complexity, renal biopsy is not a practical tool for routine use in research or clinical care. Therefore, there is great interest in the development of non-invasive surrogates, such as biomarkers, to query fibrosis at the tissue level. Elevated levels of plasma fibrosis biomarkers rarely provide organ specific information but rather report on global burden of systemic disease. However, urine biomarkers report much more directly on renal specific pathology as urine is in direct contact with the renal parenchyma. We recently presented data on the utility of urine galectin-3 to predict risk of adverse events in high risk heart failure patients with renal dysfunction. Notably, urine galectin-3 was independently associated with an increased risk of death, but more importantly, urine galectin-3 levels were able to risk stratify patients with renal dysfunction into high vs. low risk groups. The overarching goal of the current proposal is to leverage biospecimens available from The Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) study to further evaluate urine galectin-3 as a new cardio-renal biomarker. Additionally, data from several mechanistic animal studies have demonstrated that aldosterone antagonism can substantially attenuate renal interstitial fibrosis leading to reduced collagen deposition. As a result of the urine biospecimen availability and the randomized anti-fibrotic intervention, the TOPCAT trial dataset and biorepository represents an ideal resource for an Exploratory/Developmental Research Grant to explore urine galectin-3 as a biomarker of cardio- renal dysfunction. Our aims are to 1) Determine if urine galectin-3 levels can provide independent information regarding the risk of adverse clinical outcomes and differentiate high vs. low risk forms of renal dysfunction in patients with heart failure. 2) To determine if urine galectin-3 levels correlate with a validated marker of renal tissue fibrosis, urinary amino-terminal propeptide of type III procollagen. 3) To assess whether treatment with spironolactone is associated with reductions (or attenuation in rise) of urine galectin-3 levels compared with placebo.

确定可靠的指标来评估肾纤维化，最终共同的途径 进行性肾脏疾病是最重要的。目前，黄金标准方法用于 确定肾脏纤维化的方法是通过活检获取组织。不幸的是，肾活检是在 定义侵袭性，与疼痛、瘀伤、感染等并发症有关，甚至 死亡。由于风险概况、成本和复杂性，肾活检不是一种实用的工具。 在研究或临床护理中的常规使用。因此，人们对发展……非常感兴趣 非侵入性替代物，例如生物标记物，以在组织水平上查询纤维化。高架 血浆纤维化生物标志物水平很少提供器官特异性信息，而是报告 关于系统性疾病的全球负担。然而，尿液生物标记物更直接地报告 肾脏特殊病理如尿液与肾实质直接接触。我们最近 提供了尿半乳凝素-3用于预测高危心脏不良事件风险的数据 肾功能不全的衰竭患者。值得注意的是，尿半乳凝素-3独立地与 死亡风险增加，但更重要的是，尿半乳凝素-3水平能够 将肾功能不全患者分为高风险组和低风险组。 当前提案的首要目标是利用可从 醛固酮拮抗剂治疗保留性心功能心力衰竭 (TOPCAT)的研究，以进一步评估尿半乳糖凝集素-3作为一个新的心肾生物标志物。 此外，来自几个机械动物研究的数据表明，醛固酮 拮抗剂可显著减轻导致胶原减少的肾间质纤维化 证词。由于尿液生物塞米松的可用性和随机抗纤维化 作为干预措施，TOPCAT试验数据集和生物信息库是 探索/发展研究拨款探索尿半乳糖凝集素-3作为心脏生物标志物- 肾功能不全。我们的目标是1)确定尿半乳糖凝集素-3水平是否能提供 关于不良临床结果风险的独立信息，并区分高 心力衰竭患者中肾功能不全的低风险形式。2)确定尿液是否 Galectin-3水平与肾组织纤维化的有效标志物尿氨基末端相关 III型前胶原蛋白前肽。3)评估螺内酯治疗是否有效 与尿Galectin-3水平降低(或上升)相关 安慰剂。