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

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-ß-D-glucosaminidase (NAG), and ß2-microglobulin (ß2-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.

Joint and interactive effects of metal mixtures on liver damage: Epidemiological evidence from repeated-measures study.

BACKGROUND: The impact of heavy metals on liver function has been examined in numerous epidemiological studies. However, these findings lack consistency and longitudinal validation. METHODS: In this study, we conducted three follow-up surveys with 426 participants from Northeast China. Blood and urine samples were collected, along with questionnaire information. Urine samples were analyzed for concentrations of four metals (chromium [Cr], cadmium [Cd], lead [Pb], and manganese [Mn]), while blood samples were used to measure five liver function indicators (alanine aminotransferase [ALT], aspartate aminotransferase [AST], albumin [ALB], globulin [GLB], and total protein [TP]). We utilized a linear mixed-effects model (LME) to explore the association between individual heavy metal exposure and liver function. Joint effects of metal mixtures were investigated using quantile g-computation and Bayesian kernel machine regression (BKMR). Furthermore, we employed BKMR and Marginal Effect models to examine the interaction effects between metals on liver function. RESULTS: The LME results demonstrated a significant association between urinary heavy metals (Cr, Cd, Pb, and Mn) and liver function markers. BKMR results indicated positive associations between heavy metal mixtures and ALT, AST, and GLB, and negative associations with ALB and TP, which were consistent with the g-comp results. Synergistic effects were observed between Cd-Cr on ALT, Mn-Cr and Cr-Pb on ALB, while an antagonistic effect was found between Mn-Pb and Mn-Cd on ALB. Additionally, synergistic effects were observed between Mn-Cr on GLB and Cd-Cr on TP. Furthermore, a three-way antagonistic effect of Mn-Pb-Cr on ALB was identified. CONCLUSION: Exposure to heavy metals (Cr, Cd, Mn, Pb) is associated with liver function markers, potentially leading to liver damage. Moreover, there are joint and interaction effects among these metals, which warrant further investigation at both the population and mechanistic levels.

Threshold effect of urinary chromium on kidney function biomarkers: Evidence from a repeated-measures study.

Chronic kidney disease (CKD) is a public health concern worldwide, and chromium exposure may be a risk factor due to its potential nephrotoxicity. However, research on the association between chromium exposure and kidney function especially the potential threshold effect of chromium exposure is limited. A repeated-measures study involving 183 adults (641 observations) was conducted from 2017 to 2021 in Jinzhou, China. Urinary albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) were measured as kidney function biomarkers. Generalized mixed models and two-piecewise linear spline mixed models were used to assess the dose-response relationship and potential threshold effect of chromium on kidney function, respectively. Temporal analysis was conducted by the latent process mixed model to depict the longitudinal change of kidney function over age. Urinary chromium was associated with CKD (odds ratio [OR] = 1.29; 95 % confidence interval [CI], 6.41, 14.06) and UACR (Percent change = 10.16 %; 95 % CI, 6.41 %, 14.06 %), and we did not find significant association between urinary chromium and eGFR (Percent change = 0.06 %; 95 % CI, -0.80 %, 0.95 %). The threshold analyses suggested the existence of threshold effects of urinary chromium, with inflection points at 2.74 µg/L for UACR and 3.95 µg/L for eGFR. Furthermore, we found that chromium exposure exhibited stronger kidney damage over age. Our study provided evidence for the threshold effects of chromium exposure on kidney function biomarkers and the heightened nephrotoxicity of chromium in older adults. More attention should be paid to the supervision of chromium exposure concentrations for preventing kidney damage, especially in older adults.