A probabilistic approach for benchmark dose of melamine exposure for a marker of early renal dysfunction in patients with calcium urolithiasis

Environmental exposure to melamine has been associated with early renal injury in urolithiasis patients even when urinary concentrations of melamine are low. The aim of this study was to derive a benchmark dose (BMD) for melamine for urolithiasis patients. To do this, one-spot urine sample from 309 participants was obtained to measure urinary melamine and N-acetyl β -D-glucosaminidase (NAG), an early renal damage biomarker. The participants were then classified into four exposure groups based on the outcomes of melamine tableware usage questionnaire. A beta distribution of urinary excretion fraction for each group was assumed to estimate their average daily intakes (AvDIs) of melamine. The BMD and the corresponding one-sided 95% lower bound (BMDL) was then derived based on Bayesian model averaging of alternative regression models between the participants' NAG levels and their estimated AvDIs, adjusting for age, gender, and other covariates. Bayesian Markov chain Monte Carlo simulations were used for all the estimates. With a benchmark response of 0.10, the simulated BMDL of 4.89 μg/kg-bw/day for melamine exposure threshold was much lower than the WHO's current recommended tolerable daily intake of 200 μg/kg_bw/day and the US FDA's 63 μg/kg_bw/day. The current regulation level of melamine might not safeguard urolithiasis patients from further deterioration of renal function.