Drinking Water Contaminants Linked to Higher Chronic Kidney Disease Risk

Long-term exposure to trihalomethanes (THMs), specifically brominated compounds, and even at levels below current US regulatory limits, may increase the risk of chronic kidney disease (CKD), according to a large cohort study published in JAMA Network Open.1

The US Safe Drinking Water Act requires monitoring and regulation of nearly 100 contaminants.2 However, thousands of potentially harmful chemicals are still unregulated, and research has shown that nearly one-third of Americans have been exposed to unregulated contaminants, with Hispanic and Black communities disproportionately impacted. These substances enter groundwater and surface waters through industrial activities and consumer products, posing a hidden threat to public health.

The new prospective study included 89,320 women teachers and school administrators enrolled between 1995 and 1996, with CKD outcomes tracked from 2005 to 2018.1 Investigators found a significant exposure-response association between THM concentrations in community water supplies and CKD incidence, particularly for brominated THMs, which are not separately regulated under current standards.

Over the follow-up period, 6242 incident CKD cases were identified. Researchers estimated residential exposure by calculating time-weighted mean concentrations of 4 THMs, 3 brominated (bromodichloromethane, dibromochloromethane, and bromoform), and chloroform, using annual measurements from community water systems between 1995 and 2005. Median total THM exposure was 5.5 μg/L (IQR, 0.5–24.1 μg/L; 95th percentile, 57.8 μg/L). For brominated THMs alone, the median was 2.7 μg/L (IQR, 0.7–11.3 μg/L; 95th percentile, 30.0 μg/L).

Regulators and clinicians should re-evaluate potential nephrotoxic risks from commonly used water treatment methods, researchers suggest.

Image Credit: Dusan Petkovic - stock.adobe.com

Compared with those in the lowest exposure quartile (< 0.7 μg/L), participants exposed to brominated THM levels in the 75th percentile range had a 23% higher risk of developing CKD (HR, 1.23; 95% CI, 1.13–1.33). For those at or above the 95th percentile (≥ 30.0 μg/L), the risk increased by 43% (HR, 1.43; 95% CI, 1.23–1.66; P < .001).

Mixture analysis found that brominated THMs accounted for 52.9% of the observed CKD risk, followed by uranium (35.4%), arsenic (6.2%), and chloroform (5.5%).

The biological plausibility is supported by prior animal studies showing that brominated THMs, particularly bromodichloromethane, can cause proximal tubular damage and reduced glomerular filtration rate (GFR). These compounds are also more mutagenic when metabolized via glutathione S-transferase theta 1, an enzyme abundant in renal tissue, and may disrupt collagen scaffold assembly in the glomerular basement membrane.

Additional analysis revealed that chronic exposure to bromodichloromethane within California’s proposed public health goal range (5.8–16.3 μg/L) was associated with a 15% increased CKD risk compared with ≤ 0.2 μg/L, while exposure above 16.4 μg/L (≥ 95th percentile) was linked to a 32% increased risk.

“[Total] THM exposure in this study population was well below the regulatory limit (≤ 80 μg/L), suggesting that current policy may not protect against long-term risk,” the authors wrote. “In our study, brominated THMs were associated with the greatest CKD risk and emerged as the largest contributor in our mixture analysis. Brominated THMs are not separately regulated from [total] THM, although prior evidence suggests that they may be more nephrotoxic than chloroform.”

The researchers acknowledged limitations, including the inability to account for individual-level water use behaviors, filtration practices, or nonresidential exposures. CKD diagnoses were based on administrative data, and the cohort lacked biomarkers such as proteinuria or GFR measurements. The study’s strength lies in its longitudinal design, large sample size, and detailed residential exposure tracking, the study noted.

Based on the findings, the authors suggest that regulators and clinicians alike should re-evaluate potential nephrotoxic risks from commonly used water treatment methods, especially as the global burden of CKD continues to rise.

References

1. Medgyesi DN, Mohan S, Bangia K, et al. Community water trihalomethanes and chronic kidney disease. JAMA Netw Open. 2025;8(7):e2518513. doi:10.1001/jamanetworkopen.2025.18513
2. Grossi G. Nearly one-third of Americans face unregulated contaminants in water, Hispanic, Black communities hit hardest. AJMC®. January 15, 2025. Accessed July 11, 2025. https://www.ajmc.com/view/nearly-one-third-of-americans-face-unregulated-contaminants-in-water-hispanic-black-communities-hit-hardest