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. 2015 Jul;26(4):601-12.
doi: 10.1097/EDE.0000000000000313.

The association of urine arsenic with prevalent and incident chronic kidney disease: evidence from the Strong Heart Study

Laura Y Zheng  1 , Jason G Umans, Fawn Yeh, Kevin A Francesconi, Walter Goessler, Ellen K Silbergeld, Karen Bandeen-Roche, Eliseo Guallar, Barbara V Howard, Virginia M Weaver, Ana Navas-Acien
Affiliations

The association of urine arsenic with prevalent and incident chronic kidney disease: evidence from the Strong Heart Study

Laura Y Zheng et al. Epidemiology. 2015 Jul.

Abstract

Background: Few studies have evaluated associations between low to moderate arsenic levels and chronic kidney disease (CKD). The objective was to evaluate the associations of inorganic arsenic exposure with prevalent and incident CKD in American Indian adults.

Methods: We evaluated the associations of inorganic arsenic exposure with CKD in American Indians who participated in the Strong Heart Study in 3,851 adults ages 45-74 years in a cross-sectional analysis, and 3,119 adults with follow-up data in a prospective analysis. Inorganic arsenic, monomethylarsonate, and dimethylarsinate were measured in urine at baseline. CKD was defined as estimated glomerular filtration rate ≤ 60 ml/min/1.73 m, kidney transplant or dialysis.

Results: CKD prevalence was 10.3%. The median (IQR) concentration of inorganic plus methylated arsenic species (total arsenic) in urine was 9.7 (5.8, 15.7) μg/L. The adjusted odds ratio (OR; 95% confidence interval) of prevalent CKD for an interquartile range in total arsenic was 0.7 (0.6, 0.8), mostly due to an inverse association with inorganic arsenic (OR: 0.4 [0.3, 0.4]). Monomethylarsonate and dimethylarsinate were positively associated with prevalent CKD after adjustment for inorganic arsenic (OR: 3.8 and 1.8). The adjusted hazard ratio of incident CKD for an IQR in sum of inorganic and methylated arsenic was 1.2 (1.03, 1.41). The corresponding HRs for inorganic arsenic, monomethylarsonate, and dimethylarsinate were 1.0 (0.9, 1.2), 1.2 (1.00, 1.3), and 1.2 (1.0, 1.4).

Conclusions: The inverse association of urine inorganic arsenic with prevalent CKD suggests that kidney disease affects excretion of inorganic arsenic. Arsenic species were positively associated with incident CKD. Studies with repeated measures are needed to further characterize the relation between arsenic and kidney disease development.

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Figures

Figure 1
Figure 1
Odds ratios for prevalent chronic kidney disease by total arsenic (the sum of inorganic and methylated arsenic species), inorganic arsenic (arsenate and arsenite), monomethylarsonate arsenic, and dimethylarsinate. Black lines (solid lines) represent odds ratios and 95% confidence intervals (dashed lines) based on restricted quadratic spline models for log transformed arsenic with 3 knots and adjusted as in Table 3, model 3. Gray lines (solid lines) are the odds ratios and 95% CI (dashed lines) for monomethylarsonate and dimethylarsinate after adjustment for urine inorganic arsenic levels. The reference was set at the 10th percentile of the urine arsenic biomarker distribution. Odds ratios were adjusted for age (continuous), sex, study region, body mass index (continuous), education, smoking status, diabetes status, hypertensive medication, systolic blood pressure (continuous), and fasting glucose (continuous). For inorganic plus methylated arsenic species the p-value for a linear and non-linear dose-response relationships were 0.02 and 0.13, respectively. For inorganic arsenic, the p-values for linear and non-linear dose-response were 0.01 and 0.005. For monomethylarsonate, p-values for linear and non-linear dose-response were, respectively, 0.02 and 0.19 before and 0.10 and 0.003 after adjustment for inorganic arsenic. For dimethylarsinate, p-values for linear and non-linear dose-response were 0.01 and 0.14 before and 0.92 and 0.02, after adjustment for inorganic arsenic.
Figure 2
Figure 2
Odds ratios (OR) and hazard ratios (HR) for chronic kidney disease comparing the 75th to 25th percentile of the sum of inorganic and methylated arsenic species, stratified by participant characteristics Odds ratios are adjusted for age (years), sex, study region, body mass index (continuous), education, smoking status, diabetes status, hypertensive medication, systolic blood pressure (continuous), and fasting glucose (continuous) Hazard ratios were adjusted for age (continuous), sex, body mass index (continuous), education (continuous), smoking status, diabetes status, hypertensive medication, systolic blood pressure (continuous), baseline eGFR (continuous), and fasting glucose (continuous). Baseline hazard was stratified by study region.
Figure 3
Figure 3. Hazard ratio for incident CKD by the sum of inorganic and methylated arsenic species
Lines represent hazard ratios (solid lines) and 95% confidence intervals (dashed lines) based on restricted quadratic spline models for log transformed arsenic with 3 knots. The reference was set at the 10th percentile of the urine arsenic biomarker distribution. Hazard ratios were adjusted for age (continuous), sex, body mass index (continuous), education (continuous), smoking status, diabetes status, hypertensive medication, systolic blood pressure (continuous), eGFR (continuous) and fasting glucose (continuous). Baseline hazard was stratified by study region. The p-value for linear dose-response relationship for the sum of inorganic and methylated species was 0.80 and the p-value for a non-linear dose-response was 0.69. The p-value for a linear dose-response relationship for inorganic arsenic was 0.31 and the p-value for a non-linear dose-response was 0.47. For monomethylarsonate, the p-value for a linear dose-response relationship was 0.32 and 0.23 for a non-linear dose-response relationship. For dimethylarsinate, the p-value for a linear dose-response relationship was 0.91 and 0.61 for a non-linear dose-response relationship.
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