Melamine exposure threshold in early chronic kidney disease patients – A benchmark dose approach

Abstract

Environmental melamine exposure has been associated with deteriorating kidney function in early-stage chronic kidney disease patients. In this study, a benchmark dose (BMD) approach was used to establish melamine exposure threshold in 293 patients with eGFR≥30 ml/min per 1.73 m2. The patients were enrolled 2006–2010 and followed-up for a median of 7.0 years to monitor kidney outcomes. Average daily intakes (AvDI) of melamine were estimated using one-spot urine samples collected at enrollment. BMDs and corresponding one-sided 95% lower bound (BMDLs) were derived using established dose–response models relating estimated AvDIs and dichotomous kidney outcomes: doubling of serum creatine levels, eGFR decreased > 3 ml/min per 1.73 m2 per year, and >30% decline in eGFR during the first 2 years. In addition, survival time to doubling of serum creatinine and eGFR decline over time were assessed as continuous endpoints. Given a benchmark response of 0.10, BMDLs ranged from 0.74 to 2.03 μg/kg_bw/day after Bayesian model averaging, a range one to two orders lower than the current WHO recommended tolerable daily intake of 200 μg/kg_bw/day and the US FDA’s 63 μg/kg_bw/day. Our results suggest that early-stage CKD patients should strictly refrain from using melamine tableware and related melamine-made products.

Keywords

• Average daily intake
• Bayesian model averaging
• Cox regression model
• Markov chain Monte Carlo simulations
• Mixed model