B-2 Microglobulin:Renal Biomarker Workplace U Exposure

描述（由申请方提供）：β-2-微球蛋白（B2 M）是尿液中的一种低分子量蛋白质生物标志物，用于检测近端肾小管功能的早期损伤，通常用于铀暴露的生物学评估。以前对β-2-微球蛋白的研究受到样本量小的阻碍，限制了确定铀的量、持续时间或化学形式是否影响β-2-微球蛋白水平或其他泌尿功能指标的能力。本研究将探讨使用β-2-微球蛋白作为生物标志物，使用实验室数据和职业史信息，以前收集的人口2213名工人谁以前在铀加工厂工作。具体目标是：1）描述该人群的β 2-微球蛋白水平，并将其β 2-微球蛋白水平与为同一地区未暴露社区居民人群建立的参考区间进行比较;评价重复测量工人随时间推移的趋势，以及β 2-微球蛋白预测肾功能下降的能力; 2）描述β 2-微球蛋白与其他肾功能参数的关系（血肌酐、血尿素氮、尿蛋白、血糖），并比较工人与非接触人群的相关性;（3）通过暴露量、暴露时间、暴露年龄和铀的化学形式来描述每个工人的历史铀暴露特征;（4）确定铀暴露参数与尿β 2-微球蛋白水平和其他肾功能指标水平之间的因果关系; 5）将100名工人目前尿铀水平与历史接触和β 2-微球蛋白水平联系起来。我们获得了大量具有β-2-微球蛋白测量和详细职业史数据的工人，再加上我们对该工厂工业过程的了解，为研究这种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志物的有用性，将改善美国人口老龄化工人与以前的职业铀暴露的医疗筛查和干预。

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.