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，影响儿童肾功能下降率的因素描述和了解甚少。最近的研究表明，环境中铅或镉的暴露，即使是在目前联邦政府标准认为“无毒”的水平，也可能加速成人的肾损伤和肾功能下降。暴露是常见的;美国（US）的整个人口都有一些可测量的这些物质在他们的身体。很少有研究检查了低水平重金属暴露对儿童在生长和发育的脆弱时期肾功能的风险，也没有研究检查了可能处于最高风险的CKD儿童的风险。这项拟议研究的主要目的是阐明两个潜在的危险因素，铅和镉暴露，与CKD及其在儿童中的进展的关联。我们假设铅和镉将独立地与CKD及其进展相关。 由于这一领域的研究缺乏，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病（“CkiD”）的前瞻性队列研究，该研究涉及美国540名CKD儿童。为了实现所述目标，我们建议在现有CKiD队列中进行一项横断面和前瞻性队列研究，包括：（1）通过高分辨率电感耦合等离子体质谱法测定全血铅和镉水平以及尿镉水平，以及（2）同时测定肾小球滤过率（GFR），这是测定肾功能的金标准，通过基线时和之后每两年一次的碘海醇血浆消失。将使用线性回归分析这些数据，以确定铅和镉水平之间的相关性，调整其他已知风险和混杂因素，以及：（1）GFR，和（2）年GFR下降。 铅和镉的环境来源已经得到了很好的确定，减少和治疗接触的方法也已经建立，特别是考虑到铅在过去几十年中与负面神经认知影响的关系。如果铅或镉被证明与这一脆弱人群的肾功能下降有关，则可以建议进行筛查，并考虑进行治疗，如重金属减排甚至螯合治疗。由于这是一种进行性疾病，并且较低的肾功能明显与较低的生活质量和较高的发病率和死亡率相关，因此任何可能延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和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.