Many studies compared the serum/plasma 1,25 dihydroxyvitamin D₃ (1,25(OH)₂D) and 25 hydroxyvitamin D₃ (25(OH)D) between people with and without nephrolithiasis, and their results were conflicting. After systematically searching PubMed, Web of Science, The Cochrane Library, CNKI, and the Wanfang Database, we conducted a meta-analysis. Thirty-two observational studies involving 23,228 participants were included. Meta-analysis of these studies showed that of stone formers (SFs), calcium SFs had significantly higher concentrations of 1,25(OH)₂D (weighted mean difference (WMD), 10.19 pg/mL; 95% confidence interval (CI), 4.31-16.07; p = 0.0007 and WMD, 11.28 pg/mL; 95% CI, 4.07-18.50; p = 0.002, respectively) than non-stone formers, while the levels of 25(OH)D (WMD, 0.88 ng/mL; 95% CI, -1.04-2.80; p = 0.37 and WMD, -0.63 ng/mL; 95% CI, -2.72-1.47; p = 0.56, respectively) are similar. Compared with controls and normocalciuria SFs, hypercalciuria SFs had increased circulating 1,25(OH)₂D (WMD, 9.41 pg/mL; 95% CI, 0.15-18.67; p = 0.05 and WMD, 2.75 pg/mL; 95% CI, -0.20-5.69; p = 0.07, respectively) and markedly higher 25(OH)D (WMD, 5.02 ng/mL; 95% CI, 0.99-9.06; p = 0.01 and WMD, 5.02 ng/mL; 95% CI, 2.14-7.90; p = 0.0006, respectively). Normocalciuria SFs had elevated 1,25(OH)₂D level (WMD, 6.85 pg/mL; 95% CI, -5.00-18.71; p = 0.26) and comparable 25(OH)D (WMD, 0.94 ng/mL; 95% CI, -3.55-5.43; p = 0.68). Sensitivity analysis generated similar results. Current evidence suggests that increased circulating 1,25(OH)₂D is associated with urinary stones and a higher level of circulating 25(OH)D is significantly associated with hypercalciuria urolithiasis. Further studies are still needed to reconfirm and clarify the role of vitamin D in the pathogenesis of stones.
Keywords: 1,25 dihydroxyvitamin D; 25 hydroxyvitamin D; meta-analysis; nephrolithiasis; systematic review; urolithiasis; vitamin D.