Association and mediation analyses among multiple metals exposure, plasma folate, and community-based impaired estimated glomerular filtration rate in central Taiwan.

Publisher: BioMed Central Country of Publication: England NLM ID: 101147645 Publication Model: Electronic Cited Medium: Internet ISSN: 1476-069X (Electronic) Linking ISSN: 1476069X NLM ISO Abbreviation: Environ Health Subsets: MEDLINE

Original Publication: London : BioMed Central, [2002-

Arsenic* ; Metals, Heavy* ; Renal Insufficiency, Chronic*/chemically induced ; Renal Insufficiency, Chronic*/epidemiology; Adult ; Cadmium ; Cross-Sectional Studies ; Female ; Folic Acid ; Glomerular Filtration Rate ; Humans ; Male ; Mediation Analysis ; Prospective Studies ; Taiwan/epidemiology ; Uric Acid

Background: Chronic kidney disease (CKD) is increasing, with heavy metal exposure an important risk factor. Additionally, the antioxidant folic acid has been studied for reducing blood arsenic levels and related tissue damage. Therefore, we explored the association and mediation effects among various heavy metal levels in blood, plasma folate, other CKD risk factors, and impaired estimated glomerular filtration rate (eGFR).
Methods: We constructed a community-based cross-sectional study from the Human Biomonitoring and Environmental Health Program in central Taiwan. A total of 1643 participants had lived locally for > 5 years, > 40 years old, and completely received health examinations and biospecimen collections. Impaired eGFR was defined as one single eGFR < 60 mL/min/1.73 m ² . Plasma folate and metal levels in blood were determined, as well as urinary 8-hydroxy-2'-deoxyguanosine as an oxidative stress marker. Generalized weighted quantile sum (WQS) regression analysis was used to calculate a WQS score, reflecting overall body-burden of multiple metals (arsenic, cadmium, chromium, nickel, and lead) in blood.
Results: Impaired eGFR was identified in 225 participants. Participants with high WQS scores had increased risk of impaired eGFR (odds ratio = 1.67; 95% confidence interval [CI]: 1.34, 2.07). Of five metals, arsenic, lead, and cadmium were weighted highly in impaired eGFR. Participants with high WQS and folate insufficiency (< 6 ng/mL) had 2.38-fold risk of impaired eGFR compared to those with low WQS and high folate (≥6 ng/mL) (95% CI: 1.55, 5.17). Similar increased 4.16-fold risk of impaired eGFR was shown in participants with high WQS and uric acid levels (95% CI: 2.63, 6.58). However, there were no significant WQS-folate (p = 0.87) or WQS-uric acid (p = 0.38) interactions on impaired eGFR risk. As a mediator, uric acid contributed 24% of the association between WQS score and impaired eGFR risk (p < 0.0001). However, no mediation effect of plasma folate was observed.
Conclusion: WQS analysis could be applied to evaluate the joint effects of multiple metals exposure. High WQS scores may influence impaired eGFR risk through increased uric acid levels. A large-scale and prospective cohort study is necessary to validate these results and demonstrate any causal relationship.
(© 2022. The Author(s).)

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Keywords: Chronic kidney disease; Folate; Mediation analysis; Metals; Weighted quantile sum regression

0 (Metals, Heavy)
00BH33GNGH (Cadmium)
268B43MJ25 (Uric Acid)
935E97BOY8 (Folic Acid)
N712M78A8G (Arsenic)

Date Created: 20220424 Date Completed: 20220426 Latest Revision: 20220716

20221213

PMC9034511

10.1186/s12940-022-00855-x

35461256