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.
