Cadmium risk assessment in relation to background risk of chronic kidney disease

Cadmium's noncancer effects on the kidney represent a useful case study of the unified approach to toxicity assessment described in a recent National Academy of Science report. Cadmium (Cd) is recognized to exert toxic effects on the kidney at low dose without a demonstrable threshold. The implications of current dietary exposure and regulatory limits can be understood in terms of risk for chronic kidney disease (CKD) since both Cd adverse effects and CKD are defined by the same continous parameter (loss in glomerular filtration rate [GFR]). The Cd dose response on GFR derived from a study of Swedish women was applied to the baseline population distribution of GFR to determine the effect of Cd on CKD risk. The baseline population of 47.8-yr-old women was estimated to carry a 10% rate of Stage 3 CKD, similar to national statistics in the United States. A chronic daily dose of Cd at 1 μg/kg/d produced a left shift in this distribution and increased the population risk of CKD by an estimated 25%. A 10-fold lower Cd dose was associated with an increase in population risk of 2.7%, and this rose to 3.4% in 75-yr-olds. These estimates (1) provide additional perspective to the traditional risk/no risk approaches used in setting U.S. Environmental Protection Agency (EPA) reference doses (RfD) and Agency for Toxic Substances and Disease Registry (ATSDR) minimum risk levels (MRL) and (2) demonstrate the utility of considering chemical additivity to background disease in assessing human risk.