Background: Arsenic exposure is associated with decreased kidney function. The association between low to moderate arsenic exposure and kidney disease has not been fully clarified. Study Design: The association between arsenic exposure from drinking water and chronic kidney disease (CKD) was examined in a long-term prospective observational study. Setting & Participants: 6,093 participants 40 years and older were recruited from arseniasis-endemic areas in northeastern Taiwan. Arsenic levels were 28.0, 92.8, and 295.7. μg/L at the 50th, 75th, and 90th percentiles, respectively. Predictor: Well-water arsenic and urinary total arsenic (inorganic plus methylated arsenic species) concentrations, adjusted for urinary creatinine concentration. Outcomes: Kidney diseases (ICD-9 codes: 250.4, 274.1, 283.11, 403.*1, 404.*2, 404.*3, 440.1, 442.1, 447.3, or 580-589) and CKD (ICD-9 code: 585) ascertained using Taiwan's National Health Insurance database 1998 to 2011. Measurements: HRs contrasting CKD risk across arsenic exposure levels were estimated using Cox regression. Prevalence ORs for proteinuria (protein excretion ≥ 200. mg/g) comparing quartiles of total urinary arsenic concentrations were estimated using logistic regression. Results: We identified 1,104 incident kidney disease cases, including 447 CKD cases (incidence rates, 166.5 and 67.4 per 104 person-years, respectively). A dose-dependent association between well-water arsenic concentrations and kidney diseases was observed after adjusting for age, sex, education, body mass index, cigarette smoking, alcohol consumption, and analgesic use. Using arsenic concentration ≤ 10.0μg/L as reference, multivariable-adjusted HRs for incident CKD were 1.12 (95% CI, 0.88-1.42), 1.33 (95% CI, 1.03-1.72), and 1.33 (95% CI, 1.00-1.77) for arsenic concentrations of 10.1 to 49.9, 50.0 to 149.9, and ≥150.0μg/L, respectively (P for trend=0.02). The association between arsenic concentration and kidney diseases was stronger for women (P for interaction=0.06). Arsenic values in the range of 50th to 75th and 75th to 100th percentiles of total urinary arsenic concentrations were associated with 50% and 67% higher prevalences, respectively, of proteinuria. Limitations: Kidney diseases and CKD outcomes were based on diagnostic codes. Glomerular filtration rates were not available. Other heavy metals were not measured. Conclusions: This study describes the temporal relationship between arsenic concentrations ≥ 10. μg/L in drinking water and CKD. A dose-dependent association between well-water arsenic concentration and kidney diseases was observed. Higher creatinine-adjusted urinary total arsenic concentrations were associated with a higher prevalence of proteinuria.
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