Biomarkers of Early Renal Functional Decline in Type 2 Diabetes

2 型糖尿病早期肾功能下降的生物标志物

• 批准号: 8635785
• 负责人: JOHN M. ARTHUR
• 金额: $ 32.52万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-01 至 2018-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8635785
• 关键词: Albumins; Albuminuria; Biological Assay; Biological Markers; Blood Pressure; Clinical Treatment; Collection; Complications of Diabetes Mellitus; Creatinine; Data; Development; Diabetes Mellitus; Diabetic Nephropathy; Disease; End stage renal failure; Enrollment; Future; Haptoglobins; Kidney; Kidney Diseases; Mass Spectrum Analysis; Measures; Methods; Microvascular Dysfunction; Non-Insulin-Dependent Diabetes Mellitus; Patient Care; Patients; Population; Predictive Value; Proteins; Proteomics; Randomized; Renal function; Renin-Angiotensin System; Risk; Role; Sampling; Serum; Staging; Testing; Time; Treatment Factor; Urine; Visit; aggressive therapy; base; candidate marker; cohort; conventional therapy; diabetic patient; follow-up; functional decline; glycemic control; high risk; improved; inhibitor/antagonist; macroalbuminuria; multiple reaction monitoring; novel marker; public health relevance; sample collection; urinary

Abstract Diabetic nephropathy is the leading cause of end stage renal disease in spite of improvements in therapy over the last 20 years. The identification of a biomarker that can predict which patients will lose renal function would enable better treatment for these patients. Available markers such as urinary albumin are neither sensitive nor specific. We identified urinary haptoglobin concentration as a candidate biomarker which can predict development of renal functional decline among patients with diabetes who do not yet show signs of disease. We propose to characterize the role of haptoglobin as a biomarker for the prediction of renal functional decline. The specific aims of this proposal are: 1) Determine the ability of urinary haptoglobin and other candidate biomarkers to predict early renal functional decline in patients with type 2 diabetes who have normal renal function and do not have macroalbuminuria, 2) Assess the ability of haptoglobin and other candidate biomarkers measured in serial collections of urine to predict ERFD and 3) Determine the ability of urinary haptoglobin and other candidate biomarkers to predict progression of existing diabetic kidney disease. We will use urine samples that were collected prospectively as part of the VA Glycemic Control and Complications in Diabetes Mellitus Type 2 trial (VADT). The VADT includes 1,700 subjects randomized to either intensive or conventional therapy. Follow up was at least 5 years. Mean duration of diabetes at enrollment was 11.1 years. We will use a subset of this population that includes 987 patients. We will also use prospectively collected samples to assess the ability of biomarkers to predict progression of existing kidney disease. We propose to use multiple reaction monitoring (a mass spectrometric analysis of abundance based on a stable isotopic standard) to measure urine haptoglobin concentrations as well as the concentration of a panel of additional candidate biomarkers. We will measure concentrations in serially collected samples from the VADT cohort and from the prospectively collected samples. These studies will define the ability of urine haptoglobin to predict the future development of renal functional decline in subjects without (aims 1 and 2) and with (aim 3) existing renal disease.

摘要 糖尿病肾病是终末期肾病的主要原因，尽管在治疗上有所改进 在过去的20年里。鉴定一种生物标志物，可以预测哪些患者将失去肾功能 这将有助于更好地治疗这些患者。可用的标记物，如尿白蛋白， 既不敏感也不具体。我们将尿结合珠蛋白浓度确定为候选生物标志物 它可以预测糖尿病患者肾功能下降的发展， 疾病的迹象。我们建议将触珠蛋白作为生物标志物， 肾功能下降。 本研究的具体目的是：1）测定尿结合珠蛋白和其他候选物的能力 生物标志物预测肾功能正常的2型糖尿病患者早期肾功能下降 功能和没有大量白蛋白尿，2）评估结合珠蛋白和其他候选人的能力 在连续收集的尿液中测量的生物标志物以预测ERFD，和3）确定尿生物标志物的能力， 结合珠蛋白和其他候选生物标志物来预测现有糖尿病肾病的进展。 我们将使用前瞻性采集的尿液样本作为VA Glycoprotein Control的一部分， 2型糖尿病并发症试验（VADT）。VADT包括1，700名受试者，随机分配至 强化或常规治疗。随访至少5年。糖尿病平均病程 入组时间为11.1年。我们将使用该人群的一个子集，包括987例患者。我们还将 使用前瞻性收集的样本评估生物标志物预测现有疾病进展的能力 肾病 我们建议使用多反应监测（基于一个质谱分析丰度）。 稳定同位素标准）来测量尿触珠蛋白浓度以及 一组额外的候选生物标志物。我们将测量连续收集的样品中的浓度， VADT队列和前瞻性收集的样本。这些研究将确定尿液 结合珠蛋白预测无肾功能下降受试者的未来发展（目的1和2） 和（目的3）现有的肾脏疾病。