TY - JOUR
T1 - Association of single and joint metals with albuminuria and estimated glomerular filtration longitudinal change in middle-aged adults from Spain
T2 - The Aragon workers health study
AU - Grau-Perez, Maria
AU - Domingo-Relloso, Arce
AU - Garcia-Barrera, Tamara
AU - Gomez-Ariza, Jose L.
AU - Leon-Latre, Montserrat
AU - Casasnovas, J. Antonio
AU - Moreno-Franco, Belen
AU - Laclaustra, Martin
AU - Guallar, Eliseo
AU - Navas Acien, Ana
AU - Pastor-Barriuso, Roberto
AU - Redon, Josep
AU - Tellez-Plaza, Maria
N1 - Funding Information:
Other metals. In our study, increased urine Cu (median = 10.3 μg/L) was associated with higher ACR in cross-sectional analysis, and with higher odds of ACR increase ≥20%. Cu is an essential nutrient needed for proper renal function (Palvelková, M., et al., 2018). Indeed, studies suggest that Cu–Zn imbalance induces tubular damage (Palvelková, M., et al., 2018; Nogawa et al., 1984; Eom et al., 2020). Alternatively, the potential toxicity of Cu excess is receiving increasing attention (Stern, 2010). For instance, higher urine Cu levels have been cross-sectionally associated with proteinuria and low eGFR in Taiwan (median = 1.5 μg/L, N = 2447) (Tsai, 2021), and with low eGFR in China (for Cu levels >20.96 μg/L, N = 3553) (Yang et al., 2019). Lastly, experimental and epidemiological evidence supports that kidney injury is a major effect of high Cd exposure (Agency for Toxic Substances and Disease Registry (ATSDR), 2012). Consistently, increased urine Cd levels were associated with higher ACR in our cross-sectional analysis, and also in other studies from the US (Buser et al., 2016; Ferraro et al., 2010), China (Zhang et al., 2015), and Spain (Grau-Perez, 2017). While we did not find a statistically significant association for Cd with longitudinal ACR or eGFR change, the longitudinal dose-response in our data was compatible a nephrotoxic role of cadmium for the evaluated renal endpoints. Overall, more longitudinal studies that evaluate the change in metal-related renal endpoints are needed, especially in populations exposed to low exposure levels (Byber et al., 2016).This work was supported by the Strategic Action for Research in Health sciences [PI15/00071], CIBER cardiovascular (CIBERCV), and the National Research Agency (AEI, PID2019-108973RB-C21), which are initiatives from Carlos III Health Institute Madrid and the Spanish Ministry of Science and Innovation, respectively, and are co-funded with European Funds for Regional Development (FEDER). The AWHS was additionally co-funded by the local Government of Aragon (Spain) through the Institute for Health Sciences of Aragon and the National Center for Cardiovascular Research at the Carlos III Health Institute in Madrid. MTP was supported by the National Institute for Occupational Safety and Health (T42 OH0008428 from the Education and Research Center for Occupational Safety and Health at the Johns Hopkins Bloomberg School of Public Health) and the Third AstraZeneca Award for Spanish Young Researchers. MGP and ADR received the support of a fellowship from “la Caixa” Foundation (ID 100010434, fellowships codes LCF/BQ/DI18/11660001 and LCF/BQ/DR19/11740016, respectively).
Funding Information:
This work was supported by the Strategic Action for Research in Health sciences [ PI15/00071 ], CIBER cardiovascular ( CIBERCV ), and the National Research Agency ( AEI , PID2019-108973RB-C21 ), which are initiatives from Carlos III Health Institute Madrid and the Spanish Ministry of Science and Innovation , respectively, and are co-funded with European Funds for Regional Development ( FEDER ). The AWHS was additionally co-funded by the local Government of Aragon (Spain) through the Institute for Health Sciences of Aragon and the National Center for Cardiovascular Research at the Carlos III Health Institute in Madrid. MTP was supported by the National Institute for Occupational Safety and Health ( T42 OH0008428 from the Education and Research Center for Occupational Safety and Health at the Johns Hopkins Bloomberg School of Public Health ) and the Third AstraZeneca Award for Spanish Young Researchers. MGP and ADR received the support of a fellowship from “la Caixa” Foundation (ID 100010434, fellowships codes LCF/BQ/DI18/11660001 and LCF/BQ/DR19/11740016 , respectively).
Publisher Copyright:
© 2022 Elsevier Ltd
PY - 2023/2/1
Y1 - 2023/2/1
N2 - The nephrotoxicity of low-chronic metal exposures is unclear, especially considering several metals simultaneously. We assessed the individual and joint association of metals with longitudinal change in renal endpoints in Aragon Workers Health Study participants with available measures of essential (cobalt [Co], copper [Cu], molybdenum [Mo] and zinc [Zn]) and non-essential (As, barium [Ba], Cd, chromium [Cr], antimony [Sb], titanium [Ti], uranium [U], vanadium [V] and tungsten [W]) urine metals and albumin-to-creatinine ratio (ACR) (N = 707) and estimated glomerular filtration rate (eGFR) (N = 1493) change. Median levels were 0.24, 7.0, 18.6, 295, 3.1, 1.9, 0.28, 1.16, 9.7, 0.66, 0.22 μg/g for Co, Cu, Mo, Zn, As, Ba, Cd, Cr, Sb, Ti, V and W, respectively, and 52.5 and 27.2 ng/g for Sb and U, respectively. In single metal analysis, higher As, Cr and W concentrations were associated with increasing ACR annual change. Higher Zn, As and Cr concentrations were associated with decreasing eGFR annual change. The shape of the longitudinal dose-responses, however, was compatible with a nephrotoxic role for all metals, both in ACR and eGFR models. In joint metal analysis, both higher mixtures of Cu–Zn–As–Ba–Ti–U–V–W and Co–Cd–Cr–Sb–V–W showed associations with increasing ACR and decreasing eGFR annual change. As and Cr were main drivers of the ACR change joint metal association. For the eGFR change joint metal association, while Zn and Cr were main drivers, other metals also contributed substantially. We identified potential interactions for As, Zn and W by other metals with ACR change, but not with eGFR change. Our findings support that Zn, As, Cr and W and suggestively other metals, are nephrotoxic at relatively low exposure levels. Metal exposure reduction and mitigation interventions may improve prevention and decrease the burden of renal disease in the population.
AB - The nephrotoxicity of low-chronic metal exposures is unclear, especially considering several metals simultaneously. We assessed the individual and joint association of metals with longitudinal change in renal endpoints in Aragon Workers Health Study participants with available measures of essential (cobalt [Co], copper [Cu], molybdenum [Mo] and zinc [Zn]) and non-essential (As, barium [Ba], Cd, chromium [Cr], antimony [Sb], titanium [Ti], uranium [U], vanadium [V] and tungsten [W]) urine metals and albumin-to-creatinine ratio (ACR) (N = 707) and estimated glomerular filtration rate (eGFR) (N = 1493) change. Median levels were 0.24, 7.0, 18.6, 295, 3.1, 1.9, 0.28, 1.16, 9.7, 0.66, 0.22 μg/g for Co, Cu, Mo, Zn, As, Ba, Cd, Cr, Sb, Ti, V and W, respectively, and 52.5 and 27.2 ng/g for Sb and U, respectively. In single metal analysis, higher As, Cr and W concentrations were associated with increasing ACR annual change. Higher Zn, As and Cr concentrations were associated with decreasing eGFR annual change. The shape of the longitudinal dose-responses, however, was compatible with a nephrotoxic role for all metals, both in ACR and eGFR models. In joint metal analysis, both higher mixtures of Cu–Zn–As–Ba–Ti–U–V–W and Co–Cd–Cr–Sb–V–W showed associations with increasing ACR and decreasing eGFR annual change. As and Cr were main drivers of the ACR change joint metal association. For the eGFR change joint metal association, while Zn and Cr were main drivers, other metals also contributed substantially. We identified potential interactions for As, Zn and W by other metals with ACR change, but not with eGFR change. Our findings support that Zn, As, Cr and W and suggestively other metals, are nephrotoxic at relatively low exposure levels. Metal exposure reduction and mitigation interventions may improve prevention and decrease the burden of renal disease in the population.
KW - Albuminuria
KW - Glomerular filtration rate
KW - Kidney damage
KW - Kidney function
KW - Metal mixtures
KW - Metals
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U2 - 10.1016/j.envpol.2022.120851
DO - 10.1016/j.envpol.2022.120851
M3 - Article
C2 - 36509352
AN - SCOPUS:85144553053
SN - 0269-7491
VL - 318
JO - Environmental Pollution
JF - Environmental Pollution
M1 - 120851
ER -