Associations between 25-hydroxyvitamin D/calcium/alkaline phosphatase levels and the risk of developing kidney stones: Results from NHANES (2013-2018)-based and Mendelian randomization studies.

This study explores the relationship between 25-hydroxyvitamin D/calcium/alkaline phosphatase (ALP) levels and kidney stone development via cross-sectional and Mendelian randomization (MR) analyses. We used data from the National Health and Nutrition Examination Survey (NHANES) 2013 to 2018 to explore the associations of 25(OH)D metabolite, calcium, and ALP levels with kidney stone development, LDSC analysis to determine the associations between their genetically predicted levels and kidney stone development, and MR analysis to determine the causality of those relationship via genome-wide association studies (GWASs). The cross-sectional study revealed a relationship between ALP levels and kidney stone development (Model 1: OR = 1.004, 95% CI = 1.001-1.007, P = .005; Model 2: OR = 1.004, 95% CI = 1.001-1.007, P = .007; Model 3: OR = 1.003, 95% CI = 1.001-1.006, P = .011) in both men and women. LDSC analysis also revealed a genetic correlation between ALP concentrations and kidney stone development (ukb-b-18372: rg = 0.296, P = 1.45E-04; GCST90044237: rg = 0.157, P = .004). The results of both MR analyses demonstrated that kidney stones cause elevated ALP levels (IVW: OR = 2.233, 95% CI = 1.113-4.480, P = .024, preliminary analysis; OR = 1.003, 95% CI = 1.000-1.005, P = .025, validation analysis). MR analysis also revealed that elevated serum calcium levels increased the risk of developing kidney stones (IVW: OR = 1.002, 95% CI = 1.000-1.003, P = 4.258E-04, preliminary analysis; OR = 1.592, 95% CI = 1.365-1.858, P = 3.367E-09, validation analysis). Our study strongly supports a positive association between kidney stone development and ALP levels. Although observational studies did not reveal an association between calcium levels and kidney stone development, MR analysis suggested a positive association between calcium levels and kidney stone development. Our study provides new and more reliable evidence and research directions for the prevention, diagnosis and treatment of kidney stones.