| Title: | Residential water hardness and incident chronic kidney disease: A causal inference analysis in a prospective cohort study |
| Journal: | Journal of Hazardous Materials Advances |
| Published: | 1 Apr 2026 |
| DOI: | https://doi.org/10.1016/j.hazadv.2026.101187 |
Publication 18126
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Abstract
Background Chronic kidney disease (CKD) poses a global health burden, yet the impact of drinking water mineral content - especially hardness - on CKD development is poorly understood and causal evidence is limited. This study investigated the association between long-term exposure to water hardness and incident CKD risk using causal-inference approaches. Methods We followed 488,663 UK Biobank participants enrolled 2006-2010 without CKD for ≥1 year, tracking health outcomes to 2022 via linked records. Residential water hardness (CaCO3 equivalents, Ca, Mg) was quantified by postcode and analyzed as USGS/WHO categories, quartiles, and continuous variables. Incident CKD (ICD-10 N18) associations were assessed using multivariable Cox models adjusted for demographics, lifestyle, clinical factors, and PRS tertiles. Nonlinear trends were evaluated with penalized splines. To probe causality, we implemented causal-inference approaches including generalized propensity score-adjusted and inverse-probability weighting-weighted modeling. Results Over a median follow-up of 13.7 years, 21,091 of 488,663 participants (4.3%) developed CKD. Compared with the lowest CaCO3 quartile, the highest quartile had a HR of 1.05 (95% CI 1.01-1.10). CaCO3, Ca, and Mg per IQR were associated with HRs of 1.03 (1.00-1.06), 1.12 (1.08-1.16), and 1.08 (1.07-1.09), respectively. USGS moderate (60-120 mg/L) and very hard (>180 mg/L) categories, and WHO-defined hardness (≥200 mg/L), showed elevated CKD hazards. Nonlinear splines indicated plateauing at high concentrations. Causal analyses produced broadly concordant mineral-specific signals, although composite CaCO3 patterns were sensitive to model specification. Stronger associations were observed among older adults, smokers, unemployed participants, non-diabetics, and participants with hypertension, with no modification by sex or genetic risk. Conclusions Elevated domestic water hardness - particularly Ca and Mg concentrations - was modestly associated with increased CKD risk, suggesting the potential inclusion of water mineral content in renal disease prevention strategies. While causal-inference methods largely corroborated mineral-specific associations, definitive causal claims remain limited by exposure misclassification, potential unmeasured co-contaminants, and the assumptions underlying GPS/IPW. Further studies with individual-level water measurements and broader contaminant panels are needed.</p>
7 Authors
- Xiaoyu Sun
- Jinwei Wang
- Chao Yang
- Xueyan Bian
- Jianwei Ma
- Feifei Zhang
- Luxia Zhang
1 Application
| Application ID | Title |
|---|---|
| 90018 | Environment, genotype, AI-derived phenotype, and the risk of cardiovascular diseases, metabolic diseases, and chronic kidney disease |
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