Causal association of genetically predicted urinary sodium–potassium ratio and upper urinary calculi

The causality between the urinary sodium–potassium ratio and upper urinary calculi has not been clarified and easily affected by confounders. We performed two-sample and multivariable Mendelian randomization (MR) analysis to evaluate the potential causal role of the urinary sodium–potassium ratio in upper urinary calculi. Data of the urinary sodium–potassium ratio (N = 326,938), upper urinary calculi (N = 337,199), and confounding factors including BMI (N = 336,107), ever-smoke (N = 461,066), hypertension (N = 218,754), diabetes (N = 218,792), and alcohol intake frequency (N = 462,346) were obtained from the IEU OpenGWAS Project database. The inverse-variance weighted (IVW), weighted median, and MR-Egger methods were used to estimate MR effects. The MR-Egger intercept test, Cochran's Q test, MR-PRESSO, leave-one-out method, and funnel plot were used for sensitivity analysis. A causal relationship was found between the urinary sodium–potassium ratio and upper urinary calculi (OR = 1.008, 95% CI = 1.002–1.013, P = 0.011). FinnGen data supported this conclusion (OR = 2.864, 95% CI = 1.235–6.641, P = 0.014). The multivariable Mendelian randomization analysis result showed that after adjusting for the effects of five confounders, the urinary sodium–potassium ratio was still positively correlated with upper urinary calculi (OR = 1.005, 95% CI = 1.001–1.009, P = 0.012). This study demonstrated a positive causal association between the urinary sodium–potassium ratio and upper urinary calculi using MR analysis. Timely identification of changes in urine composition and dietary regulation of sodium and potassium intake could greatly reduce the incidence of future urinary calculi.