The Association of Urine Arsenic with Prevalent and Incident Chronic Kidney Disease

Zheng, Laura; Umans, Jason G.; Yeh, Fawn; Francesconi, Kevin A.; Goessler, Walter; Silbergeld, Ellen K.; Bandeen‐Roche, Karen; Güallar, Eliseo; Howard, Barbara V.; Weaver, Virginia M.; Navas‐Acien, Ana

doi:10.1097/ede.0000000000000313

Cited by 84 publications

(64 citation statements)

References 55 publications

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“…Our contention that InAs excretion is impaired among those with reduced renal function is also supported by recent cross-sectional and prospective analyses of a large American Indian cohort with substantially lower As exposure than our study population (median total uAs 9.7 μg/L vs. 125 μg/L in our study) (Zheng et al, 2015). In the cross-sectional analysis of that cohort, urinary InAs concentrations were inversely associated with CKD prevalence (i.e.…”

Section: Discussionsupporting

confidence: 87%

Renal function is associated with indicators of arsenic methylation capacity in Bangladeshi adults

Peters

Hall

Liu

et al. 2015

Environmental Research

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Background Arsenic (As) methylation capacity in epidemiologic studies is typically indicated by the proportions of inorganic As (%InAs), monomethylarsonic acid (%MMA), and dimethylarsinic acid (%DMA) in urine as a fraction of total urinary As. The relationship between renal function and indicators of As methylation capacity has not been thoroughly investigated. Objectives Our two aims were to examine (1) associations between estimated glomerular filtration rate (eGFR) and %As metabolites in blood and urine, and (2) whether renal function modifies the relationship of blood %As metabolites with respective urinary %As metabolites. Methods: In a cross-sectional study of 375 As-exposed Bangladeshi adults, we measured blood and urinary As metabolites, and calculated eGFR from plasma cystatin C. Results In covariate-adjusted linear models, a one ml/min/1.73 m2 increase in eGFR was associated with a 0.39% increase in urinary %InAs (p<0.0001) and a mean decrease in urinary %DMA of 0.07 (p=0.0005). In the 292 participants with measurable blood As metabolites, the associations of eGFR with increased blood %InAs and decreased blood %DMA did not reach statistical significance. eGFR was not associated with urinary or blood %MMA in covariate-adjusted models. For a given increase in blood %InAs, the increase in urinary %InAs was smaller in those with reduced eGFR, compared to those with normal eGFR (p=0.06); this effect modification was not observed for %MMA or %DMA. Conclusions Urinary excretion of InAs may be impaired in individuals with reduced renal function. Alternatively, increased As methylation capacity (as indicated by decreased urinary %InAs) may be detrimental to renal function.

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Section: Discussionsupporting

confidence: 87%

Renal function is associated with indicators of arsenic methylation capacity in Bangladeshi adults

Peters

Hall

Liu

et al. 2015

Environmental Research

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“…Both of these studies accounted for urine concentration by correction with urine creatinine (i.e., exposure categorized as μg/g creatinine). However, a recent study in the Strong Heart cohort reported that the sum of inorganic and methylated arsenic species was inversely related to prevalent CKD and thus, similar to the positive associations we observed (Zheng et al, in press). Interestingly, arsenic was associated with increased risk for incident CKD.…”

Section: Discussionsupporting

confidence: 88%

Association of arsenic with kidney function in adolescents and young adults: Results from the National Health and Nutrition Examination Survey 2009–2012

Weidemann

Kuo

Navas‐Acien

et al. 2015

Environmental Research

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Background Long-term exposure to arsenic is a major public health concern. Emerging evidence suggests adverse health effects even at low levels of exposure. This study examined the association of arsenic exposure with estimated glomerular filtration rate (eGFR) and compared methods of adjustment for urinary dilution in a representative sample of U.S. adolescents and young adults. Methods We performed a cross-sectional study of 1,253 participants ages 12–30 years in the 2009–2012 National Health and Nutrition Examination Survey (NHANES) with available urinary arsenic and eGFR measures. Multivariable linear regression was used to model the association of urinary total arsenic and dimethylarsinate (DMA) with eGFR. Results The median urinary total arsenic and DMA concentrations were 6.3 μg/L (IQR 3.3 – 12.7 μg/L) and 3.3 μg/L (IQR 1.7 – 5.7 μg/L), respectively. Median eGFR was 109 mL/min/1.73 m2. Adjusting arsenic for urine concentration with urinary creatinine, eGFR was 4.0 mL/min/1.73 m2 higher (95% confidence interval [CI] 1.0 to 7.1 mL/min/1.73 m2) and 4.3 mL/min/1.73 m2 higher (95% CI 0.5 to 8.0 mL/min/1.73 m2) per log-unit increase in total arsenic and DMA, respectively. When using urine osmolality to adjust for urine concentration, a log-unit increase in total arsenic and DMA was associated with a 0.4 mL/min/1.73 m2 (95% CI −1.8 to 1.1 mL/min/1.73 m2) and 0.01 (95% CI −1.9 to 1.9 mL/min/1.73 m2) lower eGFR, respectively. Conclusions Discordant associations were observed between arsenic and eGFR levels depending on whether urinary creatinine or osmolality was used to adjust for urine concentration. Further study should be dedicated to validating the best approach to account for urinary dilution in research in toxicants, and this may have implications for all studies which examine urinary biomarkers.

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“…Experimental and epidemiological studies support the role of chronic iAs exposure in arsenic toxicity (Hughes 2002). In particular, iAs exposure has been associated with cancer [International Agency for Research on Cancer (IARC) 2004], cardiometabolic disease (Moon et al 2012; Navas-Acien et al 2008), and kidney disease (Peters et al 2014; Zheng et al 2015). After entering the body, iAs undergoes two sets of reduction and methylation reactions to a trivalent state and oxidation to a pentavalent state, producing monomethylarsonate (MMA) and then dimethylarsinate (DMA) (Hughes 2002).…”

Section: Introductionmentioning

confidence: 99%

Association of Cardiometabolic Genes with Arsenic Metabolism Biomarkers in American Indian Communities: The Strong Heart Family Study (SHFS)

Balakrishnan

Vaidya

Franceschini³

et al. 2017

Environ Health Perspect

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Background:Metabolism of inorganic arsenic (iAs) is subject to inter-individual variability, which is explained partly by genetic determinants.Objectives:We investigated the association of genetic variants with arsenic species and principal components of arsenic species in the Strong Heart Family Study (SHFS).Methods:We examined variants previously associated with cardiometabolic traits (~ 200,000 from Illumina Cardio MetaboChip) or arsenic metabolism and toxicity (670) among 2,428 American Indian participants in the SHFS. Urine arsenic species were measured by high performance liquid chromatography–inductively coupled plasma mass spectrometry (HPLC-ICP-MS), and percent arsenic species [iAs, monomethylarsonate (MMA), and dimethylarsinate (DMA), divided by their sum × 100] were logit transformed. We created two orthogonal principal components that summarized iAs, MMA, and DMA and were also phenotypes for genetic analyses. Linear regression was performed for each phenotype, dependent on allele dosage of the variant. Models accounted for familial relatedness and were adjusted for age, sex, total arsenic levels, and population stratification. Single nucleotide polymorphism (SNP) associations were stratified by study site and were meta-analyzed. Bonferroni correction was used to account for multiple testing.Results:Variants at 10q24 were statistically significant for all percent arsenic species and principal components of arsenic species. The index SNP for iAs%, MMA%, and DMA% (rs12768205) and for the principal components (rs3740394, rs3740393) were located near AS3MT, whose gene product catalyzes methylation of iAs to MMA and DMA. Among the candidate arsenic variant associations, functional SNPs in AS3MT and 10q24 were most significant (p < 9.33 × 10–5).Conclusions:This hypothesis-driven association study supports the role of common variants in arsenic metabolism, particularly AS3MT and 10q24.Citation:Balakrishnan P, Vaidya D, Franceschini N, Voruganti VS, Gribble MO, Haack K, Laston S, Umans JG, Francesconi KA, Goessler W, North KE, Lee E, Yracheta J, Best LG, MacCluer JW, Kent J Jr., Cole SA, Navas-Acien A. 2017. Association of cardiometabolic genes with arsenic metabolism biomarkers in American Indian communities: the Strong Heart Family Study (SHFS). Environ Health Perspect 125:15–22; http://dx.doi.org/10.1289/EHP251

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The Association of Urine Arsenic with Prevalent and Incident Chronic Kidney Disease

Cited by 84 publications

References 55 publications

Renal function is associated with indicators of arsenic methylation capacity in Bangladeshi adults

Renal function is associated with indicators of arsenic methylation capacity in Bangladeshi adults

Association of arsenic with kidney function in adolescents and young adults: Results from the National Health and Nutrition Examination Survey 2009–2012

Association of Cardiometabolic Genes with Arsenic Metabolism Biomarkers in American Indian Communities: The Strong Heart Family Study (SHFS)

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