Susceptibility to Environmental Heavy Metal Toxicity among Americans with Kidney Disease

The consequences of low levels of environmental heavy metal exposure, as found widely in the United States, in those with impaired renal function remain underexplored.

We examined the cross-sectional association of indices of renal function with lead and cadmium levels in blood and urine among National Health and Nutrition Examination Survey (NHANES) participants. We used the 1999-2002 cycle, which included measures of cystatin C, in order to quantify renal function most precisely and defined chronic kidney disease (CKD) as an estimated glomerular filtration rate (eGFR) <60 ml/min per 1.73 m².

In weighted and adjusted analyses of 5638 participants, lead levels were 0.23 (95% CI, 0.03 to 0.42) μg/dl higher among participants with CKD, and 0.05 (95% CI, 0.01 to 0.09) μg/dL higher per 10 ml/min per 1.73 m² lower eGFR. Cadmium levels were 0.02 (95% CI, 0.01 to 0.03) μg/L higher per 10 ml/min per 1.73 m² lower eGFR. Black race significantly modified the association of lower eGFR with higher circulating lead levels (P interaction <0.001). A 10 ml/min per 1.73 m² lower eGFR was associated with a 0.13 (95% CI, 0.06 to 0.21) μg/dl higher lead level among Black participants compared with 0.03 (95% CI, -0.04 to 0.11) μg/dl higher level among White participants. Among the 1852 participants with urinary metal measurements, despite higher circulating levels, those with CKD had significantly lower urinary lead levels (-0.16 [95% CI, -0.30 to -0.01] ng/ml) and urinary lead/creatinine ratios (-0.003 [95% CI, -0.004 to -0.001]).

CKD is associated with higher blood lead levels, particularly among Blacks, and simultaneously, lower urinary lead levels, consistent with the hypothesis that CKD confers a state of heighted susceptibility to heavy metal environmental exposure by reducing its elimination. Given that low levels of exposure remain highly prevalent in the United States, further efforts to protect patients with CKD from heavy metal toxicity may be warranted.