Associations between co-exposure of metals and the renal tubular damage of the residents in the metal contaminated smelter area

Abstract

Background and aim: The effects of metals to renal tubular damage have been mostly reported for individual metals. We investigated non-linear effects of multiple metals for renal tubular damage and interactions among metals of the real population living near the metal contaminated smelter area. Methods: A total of 120 individuals were included for urine sampling and survey in the Forensic Research via Omics Markers(FROM) study. Nine metals(V, Cr, Mn, Ni, Mo, Cd, Sb, Pb, and Hg) in urine were analyzed by inductively coupled plasma-mass spectroscopy and mercury analyzer. Beta-2-microglobulin(β2-MG) and N-acetyl-β-D-glucosaminidase(NAG) were applied as renal tubular damage markers. We compared the difference between the single-metal models and the multiple-metal models. And Bayesian kernel machine regression(BKMR) was conducted to examine the joint effects of multiple metals on renal tubular damage, interactions among metals and non-linear dose-response effects. Results: V for β2-MG, and Hg and Cd for NAG were consistently significant in both simple and multiple linear regression, though Ni for β2-MG was significant only in the multiple linear regression model. Mn for NAG was significant only in the single linear regression model. The BKMR analysis showed that the co-exposure of metals was significantly increased only NAG and Hg contributed the most to the NAG(PIP, posterior inclusion probability=0.608). β2-MG was increased by co-exposure of metals but not statistically significant and V contributed the most to the β2-MG(PIP=0.704). Conclusions: This study suggests that co-exposure of metals was significantly associated with NAG. The interaction among metals for renal tubular damage was not shown but further study is needed. Keywords: Metals, Co-exposure, Kidney damage, BKMR, Metal exposure The Korea Environment Industry and Technology Institute through the Core Technology Development Project for Environmental Disease Prevention and Management, funded by the Korea Ministry of Environment (grant number 2021003320003).