Background Kidney stone disease is a common global urological problem influenced by inflammatory, clinical, demographic, and genetic factors, with genetics estimated to account for up to 50% of susceptibility. However, few studies have comprehensively evaluated genetic polymorphisms alongside clinical and demographic determinants, and the underlying mechanisms linking these risk factors to stone formation remain insufficiently understood. This study aimed to clarify how these factors contribute to kidney stone occurrence to support preventive strategies. Methods A case-control study was conducted at a tertiary referral center from April 2021 to September 2022, including 306 participants (153 cases and 153 controls). Demographic information was obtained through interviews, biometry data and blood pressure data were collected during screening. While biochemical and genetic polymorphism analyses were performed using blood specimens. Morning urine samples were used for urinalysis, and 24-hour urine collections assessed urinary solutes and pH. Fluid intake was measured using the Liq-In7 questionnaire. Bivariate and multivariate analyses were conducted using SPSS version 25, and path analysis was performed using R version 4.4.3. Results Multivariate analysis showed that older age, higher serum creatinine, elevated urinary calcium, urinary tract infection, and several genetic variants (CaSR rs1801725 GT; CLDN14 rs219780 CT; VDR rs2228570 AG/GG; VDR rs1544410 CT; ALPL rs1256328 CT) were associated with an increased risk of kidney stones. Conversely, higher urinary citrate and the CaSR rs1042636 AG genotype were protective. Although the case group had lower fluid intake, lower urinary uric acid, higher serum uric acid, fewer office workers, and a lower proportion of the VDR rs731236 CT genotype, these factors were not independent predictors. Path analysis indicated that VDR rs1544410, CLDN14 rs219780, CaSR rs1801725, CaSR rs1042636, serum creatinine, and age exerted predominantly direct effects on stone formation. These findings highlight key modifiable and non-modifiable risk factors that may guide strategies for primary prevention of kidney stones. Conclusion The study demonstrates that kidney stone etiology arises from the interaction of genetic susceptibility with clinical and lifestyle factors. These results highlight the potential for genetic screening and composite risk models to improve prevention and personalized management.
Atmoko et al. (Mon,) studied this question.