Community Water Trihalomethanes and Chronic Kidney Disease.

Importance: Over 90% of the US population relies on community water supplies (CWS), which generally use chlorine for disinfection. Trihalomethanes are regulated disinfection byproducts associated with bladder cancer and adverse birth outcomes. Animal studies report trihalomethanes, especially brominated compounds, may damage kidney function, but epidemiologic research is limited. Objective: To evaluate long-term exposure to trihalomethanes in residential CWS and its association with chronic kidney disease (CKD) risk. Design, Setting, and Participants: The California Teachers Study (CTS) is an ongoing prospective cohort of female teachers and administrators enrolled between 1995 and 1996 with data linked to mortality and health care records. This cohort study analyzed CTS data from January 1, 2005, once CKD diagnostic coding was adopted, through December 31, 2018. Statistical analysis was conducted from July 2023 to December 2024. Exposures: Residence time-weighted mean concentrations of 4 trihalomethanes, including 3 brominated trihalomethanes and chloroform, were calculated using annual measurements from CWS serving participants' homes from 1995 to 2005. Uranium and arsenic (potentially nephrotoxic metals, previously evaluated in the cohort) from CWS were included as part of a g-computation mixture analysis. Main Outcomes and Measures: Cases of moderate (stage 3) to end-stage CKD were identified with diagnostic codes or dialysis-related procedures. Mixed-effects multivariable-adjusted Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs for CKD by exposure to trihalomethane levels (US maximum contaminant level of 80 μg/L). Results: The study sample included 89 320 female participants (median age, 50 years [IQR, 43-61 years]) with 6242 CKD cases. Median concentrations were 5.5 μg/L (IQR, 0.5-24.1 μg/L; 95th percentile, 57.8 μg/L) for total trihalomethanes and 2.7 μg/L (IQR, 0.7-11.3 μg/L; 95th percentile, 30.0 μg/L) for brominated trihalomethanes. In flexible spline-based models, a clear exposure-response association was observed between trihalomethanes and CKD risk, with the highest risk for brominated trihalomethanes. The HRs for CKD risk associated with brominated trihalomethanes at the highest 2 exposure categories (75th percentile and at or above the 95th percentile) were 1.23 (95% CI, 1.13-1.33) and 1.43 (95% CI, 1.23-1.66), respectively (P < .001 for trend). Brominated trihalomethanes were the largest contributor (52.9%) to the association of the overall mixture with CKD risk, followed by uranium (35.4%), arsenic (6.2%), and chloroform (5.5%). Conclusions and Relevance: In this prospective cohort study of California female teachers, exposure to trihalomethane concentrations less than 80 μg/L (US current standard) increased CKD risk, particularly brominated trihalomethanes, which are not separately regulated in community water. The findings may have public health implications given the widespread use of water chlorination and growing burden of CKD.