Abstract
OBJECTIVE: To investigate the independent associations of domestic water hardness and its primary mineral components, calcium (Ca) and magnesium (Mg), with the incidence of chronic kidney disease (CKD).</p>
PARTICIPANTS AND METHODS: This prospective cohort study included 414,587 participants from the UK Biobank. Exposures were domestic water hardness, categorized as total hardness (CaCO3), Ca, and Mg concentrations. The primary outcome was incident CKD. Multivariable Cox proportional hazards models were used to estimate HRs and 95% CIs, adjusting for a comprehensive range of demographic, lifestyle, and clinical confounders.</p>
RESULTS: Over a median follow-up of 13.2 years, 12,690 incident CKD cases were identified. Restricted cubic spline analyses revealed distinct dose-response patterns. Mg demonstrated the most substantial clinical relevance, displaying a clear linear dose-response relationship (HR, 1.46 for highest vs lowest quartile). In contrast, CaCO3 and Ca showed statistically significant nonlinear associations, with risk increasing primarily at intermediate concentrations (inverted U-shape) rather than showing a consistent linear trend. The findings remained robust across all subgroup and sensitivity analyses.</p>
CONCLUSION: Our study identifies an association between water hardness (Mg and Ca) and CKD incidence. These findings highlight water mineral composition as a potential environmental factor in renal health, although further mechanistic and geographically diverse studies are required to validate these relationships before guiding public health interventions.</p>