Causal associations of inflammatory cytokines and urinary stones: a two-sample Mendelian randomization study

Background: Prior research has shown potential changes in cytokine and growth factor levels in patients with urinary stones, but the causal relationship remains uncertain. The purpose of this study was to investigate the causal relationship between cytokine and growth factor levels and urinary tract stones. Methods: This study used a two-sample Mendelian randomization (MR) with 41 circulating cytokines and growth factors datasets alongside urinary stone disease (USD) data. It employed various analytical methods weighted median approach, simple median method, and weighted mode to establish causal relationships. Sensitivity analysis included the MR-Egger regression intercept test and Cochrane's Q statistic. Results: Using the IVW method, an increase in stem cell growth factor beta levels was associated with decreased urinary stone risk [odds ratio (OR) =0.9990; 95% confidence interval (CI): 0.9980-0.9999; P=0.04]. Conversely, an increase in interleukin-18 levels elevated the risk of urinary stones (OR =1.0012; 95% CI: 1.0002-1.0022; P=0.01). Various analytical methods consistently supported these findings. Conclusions: Our findings suggest a causal and unidirectional relationship between interleukin-18, stem cell growth factors, and USD. This indicates that these cytokines may actively contribute to the development or prevention of USD, offering a new avenue for clinical intervention based on cytokines modulation.