Association Between Serum Biochemical Parameters and Kidney Stone Disease: An Exploratory Analysis of the 2017-2018 National Health and Nutrition Examination Survey (NHANES)

Background: Kidney stone disease (KSD) is a multifactorial condition associated with individual and healthcare burden. Routine biochemical markers have yet to be fully explored for their association with KSD. Methods: This is a retrospective analysis of cross-sectional data from the 2017-2018 National Health and Nutrition Examination Survey (NHANES). Those with a complete biochemical profile and kidney stone history data were included. Weighted multivariable regression analysis was utilized to adjust for confounding factors, and false discovery rate (FDR) correction was employed to account for multiple comparisons across biochemical markers. Results: A total of 4,820 participants were included in our analysis, 477 of whom reported a history of kidney stones. The mean age was 49.48 ± 0.48 years. Serum bicarbonate was found to be significantly lower among those who reported a history of nephrolithiasis in comparison with those without in the unadjusted model (β = -0.320 mmol/L, P = 0.037), the model adjusted for age and sex (β = -0.301 mmol/L, P = 0.038), and the model adjusted for comorbidities (β = -0.340 mmol/L, P = 0.044). Following FDR, this association, however, did not remain significant across models (q = 0.296-0.352). Other biochemical parameters did not reach statistical significance for association with kidney stones in any model. Conclusion: Serum bicarbonate levels demonstrated a modest, nominally significant inverse association with a history of nephrolithiasis, but this did not persist after correction for multiple comparisons and should be interpreted with caution given the cross-sectional design of this study. No other parameter showed a significant association with kidney stones. These findings, suggesting limited utility for single-time-point biochemical testing for stone risk assessment, should be considered exploratory and hypothesis-generating rather than conclusive evidence.