B-2 Microglobulin:Renal Biomarker Workplace U Exposure

描述（由申请人提供）：β -2微球蛋白（B2 M）是尿液中的低分子量蛋白质生物标志物，用于检测近端小管功能的早期损害，通常用于铀暴露的生物学评估。先前对β -2微球蛋白的研究受到样本量小的阻碍，限制了确定铀的数量、持续时间或化学形式是否会影响β -2微球蛋白水平或其他泌尿功能指标的能力。本研究将利用实验室数据和先前收集的2213名以前在铀加工厂工作的工人的职业历史信息，探索β -2微球蛋白作为生物标志物的用途。具体目的是：1)描述该人群的β -2微球蛋白水平，并将其β -2微球蛋白水平与来自同一地区未暴露的社区居民建立的参考区间进行比较；通过反复测量评估工人的长期趋势，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、尿中血糖）的关系，并将工人与未暴露人群的关系进行比较；3)通过暴露量和暴露时间、暴露年龄和铀的化学形式来描述每个工人的铀暴露历史；4)确定铀暴露参数与尿β -2微球蛋白水平及其他肾功能指标之间的暴露-效应关系；5)将100名工人当前尿铀水平与历史暴露和β -2微球蛋白水平联系起来。我们对大量工人进行了β -2微球蛋白测量和详细的职业历史数据，再加上我们对该地点工业过程的了解，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微球蛋白作为一种生物标志物的有效性，将改善美国老年人口中既往职业性铀暴露工人的医学筛查和干预。

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.