Complex interplay of heavy metals and renal injury: New perspectives from longitudinal epidemiological evidence

Guohuan Yin; Shuanzheng Zhao; Meiduo Zhao; Jing Xu; Xiaoyu Ge; Jingtao Wu; Yifan Zhou; Xiaolin Liu; Lanping Wei; Qun Xu

doi:10.1016/j.ecoenv.2024.116424

Complex interplay of heavy metals and renal injury: New perspectives from longitudinal epidemiological evidence

Ecotoxicol Environ Saf. 2024 May 8:278:116424. doi: 10.1016/j.ecoenv.2024.116424. Online ahead of print.

Authors

Guohuan Yin¹, Shuanzheng Zhao¹, Meiduo Zhao¹, Jing Xu¹, Xiaoyu Ge¹, Jingtao Wu¹, Yifan Zhou², Xiaolin Liu³, Lanping Wei⁴, Qun Xu⁵

Affiliations

¹ Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China.
² Civil Aviation Medicine Center, Civil Aviation Administration of China, Beijing 100123, China.
³ Department of Epidemiology and Biostatistics, Jinzhou Medical University, Jinzhou, Liaoning 121001, China.
⁴ Jinzhou Central Hospital, Jinzhou, Liaoning 121001, China.
⁵ Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China. Electronic address: xuqun@ibms.cams.cn.

PMID: 38723382
DOI: 10.1016/j.ecoenv.2024.116424

Abstract

Background: Epidemiological studies have reported associations between heavy metals and renal function. However, longitudinal studies are required to further validate these associations and explore the interactive effects of heavy metals on renal function and their directional influence.

Method: This study, conducted in Northeast China from 2016 to 2021, included a four-time repeated measures design involving 384 participants (1536 observations). Urinary concentrations of chromium (Cr), cadmium (Cd), manganese (Mn), and lead (Pb) were measured, along with renal biomarkers including urinary microalbumin (umAlb), urinary albumin-to-creatinine ratio (UACR), N-acetyl-β-D-glucosaminidase (NAG), and β2-microglobulin (β2-MG) levels. Estimated glomerular filtration rate (eGFR) was calculated. A Linear Mixed Effects Model (LME) examined the association between individual metal exposure and renal biomarkers. Subsequently, Quantile g-computation and Bayesian Kernel Machine Regression (BKMR) models assessed the overall effects of heavy metal mixtures. Marginal Effect models examined the directional impact of metal interactions in the BKMR on renal function.

Result: Results indicate significant impacts of individual and combined exposures of Cr, Cd, Pb, and Mn on renal biomarkers. Metal interactions in the BKMR model were observed, with synergistic effects of Cd-Cr on NAG, umAlb, UACR; Cd-Pb on NAG, UACR; Pb-Cr on umAlb, UACR, eGFR-MDRD, eGFR-EPI; and an antagonistic effect of Mn-Pb-Cr on UACR.

Conclusion: Both individual and combined exposures to heavy metals are associated with renal biomarkers, with significant synergistic interactions leading to renal damage. Our findings elucidate potential interactions among these metals, offering valuable insights into the mechanisms linking multiple metal exposures to renal injury.

Keywords: Heavy metals; Interaction; Joint effect; Renal injury; Repeated-measures study.