The association between domestic water hardness and kidney stone disease: a prospective cohort study from the UK Biobank
Authors: Zhang Jiahao , Luo Hongcheng , Wu Haoliang , Qian Yuxin , Tang Zhicheng , Wang Juan , Li Zhibiao , Zheng Hanxiong , Tang Fucai , He Zhaohui 
Published: December 2024

Background:
Kidney stone disease is a common surgical disease and a significant public health issue, which may be influenced by environmental factors such as domestic water hardness and its related minerals. Previous studies have shown inconsistent and controversial results regarding the impact of domestic water hardness on kidney stone formation.

Methods:
This prospective cohort study analyzed data from 288 041 participants in the UK Biobank with no prior history of kidney stones from 2006 to 2024. The exposures were domestic water hardness, calcium concentration, calcium carbonate concentration, and magnesium concentration. The main outcomes were the disease status and onset time of kidney stone diseases. The confounding factors of model adjustment included age, sex, ethnicity, economic level, education level, Townsend Deprivation Index, Index of Multiple Deprivation, assessment center, body mass index, drug history influencing the metabolism of calcium and magnesium, and water intake based on the directed acyclic graph of causal hypothesis. The association between domestic water hardness and kidney stones was assessed using the Cox regression models, sensitivity analyses, subgroup and interactive analyses.

Results:
During the follow-up period, 3298 participants (1.14%) developed kidney stones. In all participants, the mean concentration of calcium, calcium carbonate, and magnesium was 52.61, 135.01, and 4.66 mg/L, respectively. In Cox regression models, higher magnesium levels (Q4, > 5 mg/L) in natural water use can reduce the risk of kidney stones [HR and 95% CI: 0.88 (0.80–0.97) in model 3], but no significant correlation was found in domestic water hardness, calcium concentration, and calcium carbonate concentration in the overall models. Four sensitivity analyses further supported the overall results in the overall models. In subgroup analysis, hard water and calcium concentration in domestic water can increase the 18%–34% incidence risk of kidney stones in participants over 60 years old and female participants; high magnesium concentration (>5 mg/L) in domestic water can decrease the 10%–28% risk of kidney stones in males, participants ≤ 45 years old, and participants without renal failure. Magnesium interacted with other minerals, and its protective effects were more significant in hard water (HR: 0.73, 95% CI: 0.61–0.87), a high concentration of CaCO3 (HR: 0.62, 95% CI: 0.50–0.78), and calcium (HR: 0.48, 95% CI: 0.33–0.71) in domestic water.

Conclusion:
Our findings suggested that magnesium levels in water can decrease kidney stone risk, but in the overall population, domestic water hardness, calcium concentration, and calcium carbonate concentration have no significant impact on the formation of kidney stones. Interestingly, hard water and its calcium concentration can promote the formation risk of kidney stones in participants > 60 years old and females, while high magnesium concentration in domestic water can reduce the risk in males, ≤ 45 years old, and those without renal failure. The protective effects of magnesium interacted with other minerals and were more obvious in the population intake of hard water and high concentrations of CaCO3 and calcium. This study contributes to the complex understanding of environmental factors in kidney stone etiology and suggests a need for focusing on mineral-specific effects in different populations and interaction with other minerals, which hope to provide some evidence of water’s role in public health and clinical management of kidney stones.