Environmental blood cadmium tracks with albuminuria at concentrations far below ToxCast AC50s.

Cadmium is a cumulative nephrotoxicant that injures the proximal tubule through oxidative stress and disrupted metal handling. Whether contemporary low-level exposure associates with albuminuria, and how those internal concentrations compare with in vitro bioactivity, remains incompletely defined. In NHANES 2011-2018 adults aged ≥40 years (n=8921; median whole-blood cadmium 0.31μg/L, 0.0028μM), survey-weighted logistic models estimated odds ratios (ORs) for albuminuria (urine albumin-to-creatinine ratio ≥30 mg/g) per doubling of whole-blood cadmium, adjusted for age, sex, race/ethnicity, poverty-income ratio, body mass index, smoking, diabetes, and hypertension. Internal concentrations were anchored to ToxCast cadmium chloride (CAS 10108-64-2) AC50s as a bioactivity exposure ratio (BER). The adjusted OR was 1.25 (95% CI 1.13-1.37) overall, a 25% higher odds of albuminuria per doubling, and 1.29 (1.09-1.52) in never-smokers; albuminuria rose across cadmium quartiles from 8.2% to 15.9%. The estimate was unchanged after further adjustment for estimated glomerular filtration rate. Median whole-blood cadmium lay about 110-fold below the 5th percentile of active AC50s (0.30 μM) but only 1.2-fold below the most potent active AC50 (0.0034 μM). Environmentally relevant cadmium therefore tracks with albuminuria at internal concentrations below most in vitro bioactivity. The BER is a screening-level scaling comparison rather than a margin of safety, and does not on its own establish an accumulation-driven mechanism.