B-2 Microglobulin:Renal Biomarker Workplace U Exposure

描述(申请人提供)：β-2-微球蛋白(B2M)是尿中的一种低分子蛋白质生物标志物，用于检测近端肾小管功能的早期损害，通常用于铀暴露的生物学评估。以前对β-2-微球蛋白的研究一直受到样本量小的限制，限制了确定铀的数量、持续时间或化学形式是否影响β-2-微球蛋白水平或其他尿功能指标的能力。这项研究将利用实验室数据和以前从2213名曾在铀加工厂工作的工人收集的职业史信息，探索将β-2-微球蛋白作为生物标志物的用途。具体目标是：1)描述该人群的β-2-微球蛋白水平，并将他们的β-2-微球蛋白水平与为来自同一地区的非暴露社区居民群体建立的参考区间进行比较；评估反复测量的工作人员随着时间的推移的趋势，以及β-2-微球蛋白预测肾功能减退的能力；2)描述β-2-微球蛋白与其他肾功能参数(血清肌酐、血尿素氮、尿蛋白、血液和尿糖)的关系，并将工人和非暴露人群的这些关系进行比较；3)通过接触铀的数量和时间、暴露年龄和铀的化学形态来描述每个工人的历史铀暴露情况；4)确定铀暴露参数和尿β2微球蛋白水平以及其他肾功能指标之间的暴露效应关系；5)将100名工人当前的尿铀水平与历史暴露水平和β2微球蛋白水平联系起来。我们通过β-2-微球蛋白测量和详细的职业史数据接触到大量工人，再加上我们对本网站工业流程的了解，为研究这一生物标志物提供了独特的机会。了解肾脏疾病的风险和β-2-微球蛋白作为生物标记物的有用性，将改善对既有职业铀暴露的美国老年人口工作者的医学筛查和干预。

DESCRIPTION (provided by applicant): Beta-2-microglobulin (B2 M) is a low molecular weight protein biomarker in urine, used in detection of early impairment of proximal tubular function, often for biological assessment of exposure to uranium. Previous studies of beta-2-microglobulin have been hampered by small sample size, limiting ability to determine if amount, duration or chemical form of uranium affects the level of beta-2-microglobulin or other measures of urinary function. This study will explore uses of beta-2-microglobulin as a biomarker using laboratory data and occupational history information previously collected from a population of 2213 workers who formerly worked at a uranium processing plant. Specific Aims are: 1) Characterize the beta-2-microglobulin levels in this population, and to compare their beta-2-microglobulin levels to reference intervals established for a population of unexposed community residents from the same region; Evaluate the trend over time in workers with repeated measures, and the ability of beta-2-microglobulin to predict diminished renal function; 2) Describe the relationship between beta-2-microglobulin and other parameters of renal function (serum creatinine, blood urea nitrogen, urinary protein, blood and glucose in urine) and compare those relationships in workers to the unexposed population; 3) Characterize the historical uranium exposure to each worker by amount and duration of exposure, age at exposure, and chemical form of uranium; 4) Determine the exposure-effect relationship between parameters of uranium exposure and level of urinary beta-2-microglobulin, and levels of other measures of renal function; 5) Relate current urine uranium levels of 100 workers to historical exposure and beta-2-microglobulin level. Our access to this large population of workers with beta-2-microglobulin measures and detailed occupational history data, coupled with our knowledge of industrial processes at this site, provides a unique opportunity to study this biomarker. Understanding risk of renal disease and usefulness of beta-2-microglobulin as a biomarker will improve medical screening and intervention in aging US population workers with previous occupational uranium exposure.