The association of lead and cadmium exposure with kidney function in children

描述(由申请人提供)： 到目前为止，影响儿童肾功能减退率的因素还很少被描述和了解。最近的研究表明，在环境中暴露于铅或镉，即使达到当前联邦政府标准所认为的“无毒”水平，也可能会加速成年人的肾脏损伤和肾功能下降。接触是很常见的；美国的所有人口体内都有一些可测量的此类物质。很少有研究研究在生长和发育的脆弱时期接触低水平重金属对儿童肾功能的风险，也没有研究在可能风险最高的CKD儿童中检查这一风险。这项拟议研究的主要目标将是阐明两个潜在的危险因素--铅和镉暴露与儿童慢性肾脏病及其进展的关系。我们假设，铅和镉将独立地与CKD及其进展相关。 由于这方面的研究很少，美国国立卫生研究院(NIH)目前正在赞助一项名为儿童慢性肾脏病(CKiD)的前瞻性队列研究，研究对象为美国540名患有慢性肾脏病的儿童。为了实现上述目标，我们建议在现有的CKiD队列中进行一项横断面和前瞻性队列研究，包括：(1)用高分辨率电感耦合等离子体质谱测定全血铅、镉和尿镉水平，以及(2)同时测量肾小球滤过率(GFR)，通过基线和每两年血浆碘己醇消失来确定肾功能的金标准。这些数据将使用线性回归进行分析，以确定铅和镉水平之间的关联，并根据其他已知的风险和混杂因素进行调整，以及：(1)GFR，(2)年度GFR下降。 铅和镉的环境来源已经确立，减少和治疗暴露的方法已经建立，特别是考虑到过去几十年铅与负面神经认知影响的联系。如果铅或镉被证明与这一脆弱人群的肾功能下降有关，可以建议进行筛查，并可以考虑治疗，如重金属消减，甚至螯合治疗。由于这是一种进行性疾病，而且肾功能低下显然与较差的生活质量和较高的发病率和死亡率有关，任何可能推迟不可避免的下降的干预措施都可能改善数千名患有肾脏疾病的儿童的生活，甚至可能改善数百万成年人的生活。

DESCRIPTION (provided by applicant): To date, factors influencing the rate of decline in kidney function in children are poorly described and understood. Recent research suggests environmental exposure to lead or cadmium, even at levels considered "non-toxic" by current federal government standards, potentially accelerates kidney injury and kidney function decline in adults. Exposure is common; the entire population of the United States (US) has some measurable amount of these substances in their body. Few studies have examined the risk of low-level heavy metal exposure on kidney function in children during vulnerable periods of growth and development, and no studies have examined this in the group likely at highest risk, children with CKD. The primary objective of this proposed study will be to elucidate the association of two potential risk factors, exposure to lead and cadmium, with CKD and its progression in children. We hypothesize that lead and cadmium will independently be associated with CKD and its progression. Due to the paucity of research in this area, the National Institutes of Health (NIH) is currently sponsoring a prospective cohort study entitled Chronic Kidney Disease in Children ("CkiD") of 540 children in the US with CKD. To accomplish the stated objectives, we propose a cross-sectional and prospective cohort study within the existing CKiD cohort to include: (1) Determination of whole blood lead and cadmium levels and urine cadmium levels by high resolution inductively coupled plasma mass spectrometry, and (2) simultaneous glomerular filtration rate (GFR) measurements, the gold-standard for the determination of kidney function, by the plasma disappearance of iohexol, at baseline and then every two years. This data will be analyzed using linear regression to determine the associations between lead and cadmium levels, adjusting for other known risk and confounding factors, and: (1) GFR, and (2) decline in annual GFR. Environmental sources of lead and cadmium are well established and methods to reduce and treat exposures have been established, especially given the association of lead with negative neurocognitive effects over the past few decades. If lead or cadmium are proven to be associated with the decline in kidney function in this vulnerable population, screening could be recommended, and treatment, such as heavy metal abatement or even chelation therapy, could be considered. As this is a progressive disease, and lower kidney function is clearly associated with poorer quality of life and higher morbidity and mortality, any intervention that could potentially delay the inevitable decline might improve the lives of thousands of children, and potentially millions of adults, with kidney disease.