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.

抽象的 尽管治疗方面有改善 在过去的20年中。可以预测哪些患者失去肾脏的生物标志物的识别 功能将为这些患者提供更好的治疗。尿白蛋白等可用标记是 既不敏感也不具体。我们确定尿触觉浓度是候选生物标志物 可以预测尚未显示的糖尿病患者肾功能下降的发展 疾病的迹象。我们建议表征触蛋白作为预测的生物标志物的作用 肾功能下降。 该提案的具体目的是：1）确定尿脱帽和其他候选者的能力 生物标志物预测患有正常肾脏的2型糖尿病患者的肾功能下降 功能并且没有大量藻尿症，2）评估触觉球蛋白和其他候选者的能力 在尿液系列中测量以预测ERFD的生物标志物和3）确定尿的能力 Haptoglobin和其他候选生物标志物可以预测现有的糖尿病肾脏疾病的进展。 我们将使用前瞻性收集的尿液样品作为VA血糖控制的一部分， 糖尿病并发症2型试验（VADT）。 VADT包括1,700名随机的受试者 强化或常规疗法。跟进至少5年。糖尿病的平均持续时间 入学人数为11。1年。我们将使用包括987名患者的该人群的一部分。我们也会 使用前瞻性收集的样品评估生物标志物预测现有的进展的能力 肾脏疾病。 我们建议使用多个反应监测（基于A的丰度的质谱分析 稳定的同位素标准）以测量尿Haptoglobin浓度以及A的浓度 其他候选生物标志物的面板。我们将测量从 VADT队列和前瞻性收集的样品。这些研究将定义尿液的能力 Haptoglobin预测没有受试者的肾功能下降的未来发展（目标1和2） 以及（AIM 3）现有的肾脏疾病。