Impact of Dietary Cadmium Intake from Rice on Renal Function Biomarker and Population Toxicokinetic Modelling

Diet is the primary pathway of human cadmium (Cd) exposure. The one-compartment toxicokinetic (TK) model conventionally links dietary Cd intake with urinary Cd (UCd) for western populations with background levels of exposure. Whether this model is applicable to high dietary Cd intake through rice has yet to be discovered. We conducted a population-based survey in a typical Cd-polluted area (n = 686) and a non-polluted area (n = 296) in China, with rice as the staple food in both areas. Furthermore, we randomly chose 34 locals to conduct a 27-month intervention by replacing home-grown high-Cd rice with market low-Cd rice. We monitored the temporal changes in Cd concentration and stable isotope signature in urine samples. The adults in the polluted area had much higher dietary Cd intakes (mean 58.5 µg kg-1 body weight month-1) and UCd (mean 13.8 µg g-1 creatinine) than those in the non-polluted area. There was a robust dose-response relationship (R2 = 0.67, n = 982) between UCd and β2-microglobulin, a biomarker of kidney impairment. The intervention reveals that a considerable proportion of Cd rapidly exuded after recent dietary intake, contradicting the conventional TK model. The modified TK model incorporating the direct blood-urine allocation greatly improved the association between dietary Cd intake and UCd. These results highlight that high dietary Cd intake through rice in China can cause dose-dependent damage to the kidney. The modified TK model can serve as a reliable model to estimate the Cd-related thresholds and the associated health risks for populations with a rice-based diet.