OBJECTIVE: This study sought to identify risk factors and develop predictive models for kidney stone disease in the U.S. population using data from the National Health and Nutrition Examination Survey (NHANES). METHODS: In a propensity score-matched cohort study, we examined the association of serum α-Klotho, hemoglobin levels, serum creatinine, and the urinary albumin-to-creatinine ratio (uACR) with kidney stone disease. RESULTS: Initially, 216,560 participants were screened
following propensity matching, 28,370 adults aged 40-79 years were included in the final analysis. Serum α-Klotho levels were inversely associated with kidney stone disease, particularly among individuals with chronic kidney disease and those who consumed alcohol. Hemoglobin levels demonstrated an inverse association with kidney stone disease risk, whereas serum creatinine levels exhibited a U-shaped relationship. No significant trend was observed for uACR overall. Low hemoglobin and α-Klotho levels, as well as elevated serum creatinine and uACR, were significantly associated with increased all-cause mortality. CONCLUSION: Our findings underscore the significance of serum α-Klotho, hemoglobin, serum creatinine, and uACR levels in assessing the risk of kidney stone disease and all-cause mortality, suggesting these markers as potential targets for prevention and management strategies. Further research is warranted to clarify the mechanisms underlying these associations.