The effects of immune cells and blood metabolites on kidney stones: a bidirectional two-sample Mendelian randomization study and mediation analysis

Immune cells are thought to play a crucial role in the pathogenesis of kidney stones (KS). However, their relationship remains controversial.

In this study, genome-wide association studies (GWAS) were utilized to obtain the 731 immune cells, 1400 blood metabolites and KS data. Inverse variable weighting (IVW) was the main analysis method in the study. In addition, we utilized a combination of analytical methods, which included MR-Egger, weighted mode, simple mode, and weighted median, to enhance the final outcomes. Stability and feasibility were verified through sensitivity analyses. Finally, we investigated the effect of immune cells that were mediated by blood metabolites on KS.

After FDR correction, immune cells had an effect on KS. CD3 on CD4+ T cells and Plasma Blast-Plasma Cell %lymphocytes were determined to be distinctly associated with KS. Other 24 types of circulating immune cells were also found to be causally related to KS. The influence of genetically predicted KS on these 26 types of circulating immune cells was not demonstrated. Further two-step MR analysis found that the associations between circulating CD3 on CD4+ T cells and Plasma Blast-Plasma Cell %lymphocytes and KS were mediated by 1,7-dimethyluric acid and 2-aminooctanoate, respectively.

Our genetic-based MR study uncovered a substantial number of immune cells potentially causally associated with KS. These results provided a prospective strategy for clinical prediction and treatment of KS.