Urinary cadmium clearance, its relationship to glomerular filtration rate and implications for cadmium epidemiology

Decreasing renal glomerular filtration rate (GFR) in association with increasing blood cadmium levels was reported in epidemiological studies of general populations. Dependence of cadmium clearance on GFR has implications for interpreting causation in these studies. Associations between cadmium clearance and creatinine clearance, a metric of GFR, were evaluated in a sample of the U.S. population. Blood to urine cadmium clearance and serum creatinine clearance were estimated in approximately 6000 individuals included in the National Health and Nutrition Examination Survey (NHANES 2009-2016). Linear regression models explained approximately 45% of variance in cadmium clearance in adults, with 74% of the explained variance attributed to creatinine clearance and 25% explained by age. In adolescents (12-<20 years), linear regression models explained 55% of variance in cadmium clearance with >99% of the explained variance attributed to creatinine clearance. The models predicted that halving creatinine clearance would result in a 40% decrease in cadmium clearance and a 20% rise in blood cadmium. Dependence of cadmium clearance on GFR has implications for assigning causation to studies in which increasing blood cadmium levels have been associated with increasing risk of low GFR. Statistical associations between blood cadmium and low GFR, such as elevated odds ratios in upper percentile strata of populations, may be partially a consequence of lower cadmium clearance in association with low GFR that is reverse causation.