To examine the independent effect of metabolic syndrome (MS) on nephrolithiasis (NL) even with changes in MS status over time.

From 2002-2003, 3872 men who were reexamined annually or biannually until 2009 were enrolled in the analysis and observed for development of NL. The examination included anthropometric measurements, biochemical measurement, and kidney ultrasonography (US). A standard Cox proportional hazards model and a time-dependent Cox model were used to calculate the adjusted hazard ratio in the NL model.

After adjusting for age, baseline glomerular filtration rate, and uric acid level, MS at baseline was associated with a significantly increased risk of NL (HR, 1.771; 95% confidence interval, 1.157-2.711). MS over time as a time-dependent variable also predicted the development of NL (HR, 1.678; 95% CI, 1.151-2.447) after adjusted baseline covariate. After adjustment for potential confounding factors, there was a significant stepwise increase in risk of NL, with each additional MS trait compared with those with no traits of MS at baseline and follow-up. As the numbers of MS traits at baseline and follow-up increased, the urine pH of participants at baseline and follow-up decreased significantly (P <.01). The prevalence of NL in participants with continual MS (6.6%) was higher than those with resolved MS, and continual MS was an independent factor to predict NL.

Our findings suggest that MS is significantly associated with increased risk of developing urine acidification, even with changes in status of MS observed during follow-up.