Cadmium and kidney function: Concentrations, variabilities, and associations across various stages of glomerular function

Data (N = 10336) from National Health and Nutrition Examination Survey for 2003–2016 for US adults aged ≥ 20 years were analyzed to evaluate the concentrations of blood and urine cadmium across the various stages of glomerular function. Estimated glomerular filtration rate (eGFR) > 90 mL/min/1.73 m2 was defined to be glomerular function stage 1 (GF-1), eGFR between 60 and 90 mL/min/1.73 m2 defined as GF-2, eGFR between 45 and 60 mL/min/1.73 m2 as GF-3A, and eGFR between 15 and 45 mL/min/1.73 m2 as GF-3B/4. Regression models stratified by GF-stages were fitted to estimate associations between the observed levels of blood and urine cadmium across stages of GF. Based on the results of stratified modes, there were consistent increases in adjusted geometric means (AGMSM) for both blood and urine cadmium from GF-1 to GF-3A although increases were not uniform from one GF stage to another. For the total population, AGMSM for blood and urine cadmium were GF-1 (0.47, 0.24), GF-2 (0.60, 0.37), GF-3A (0.72, 0.45), and GF-3B/4 (0.73, 0.45) μg/L. respectively. Although females had higher AGMSMs than males for both blood and urine cadmium, the difference in blood cadmium narrowed as kidney function deteriorated. Smokers had the steepest increases in AGMSMs for blood and urine cadmium across the stages of glomerular function and smoker-nonsmoker differences for blood cadmium narrowed as kidney function deteriorated but smoker-nonsmoker differences for urine cadmium widened as kidney function deteriorated. The important physiologic messages are that both blood and urine cadmium cease to increase from GF-3A to GF-3B/4, suggesting a new steady state based on renal failure. And, the narrowed difference in blood cadmium in smokers vs. nonsmokers suggests why this happens. Incremental exposures to cadmium are offset by excretion as renal failure progresses.