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Association of Topiramate use with Current Stone Activity -- A Population Based Analysis
James M. Jones, III, BA1, Christopher C. Robertson, MD2, Vernon M. Pais, Jr., MD2.
1Geisel School of Medicine at Dartmouth, Hanover, NH, USA, 2Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA.

Background: It is recognized that topiramate use may affect risk of stone disease. While demonstrated in single institution retrospective studies, large nationally based evaluations are absent. Furthermore, the suspected increased odds of stone disease have remained unquantified. We thus leveraged the nationally representative National Health and Nutrition Examination Survey (NHANES) to perform a population-based assessment of the association of current topiramate use on occurrence of stones presenting within the year immediately preceding survey participation.
Methods: We utilized the 2017-2020 (Pre-COVID-19) NHANES data to assess the association between current topiramate use and incidence of kidney stones. The dependent variable was the question “In the past 12 months have you passed a kidney stone?” from the Computer-Assisted Personal Interview section of the NHANES, and independent variable was the use of topiramate or phentermine-topiramate as reported on the Prescription Medications subsection of the Sample Person Questionnaire Interview. Covariates were only included if they showed significant association with topiramate use on univariate analysis. Participants under 20 years of age were excluded due to the lack of survey data on this demographic. Weights and strata provided by NHANES were employed and analyses were performed using survey package for STATA v14.
Results: 843 participants met analysis criteria, weighted to represent a nationally representative population of 23,064,066 noninstitutionalized US adults. Logistic regression was used to analyze the relationship between the incidence of kidney stone passage in the last 12 months and current topiramate use. It was found that current topiramate use was associated with a statistically significant 8.1-fold increase in the odds of stone passage in the last 12 months (OR: 8.1, 95%CI [1.04 - 63.06], p = 0.046). None of the investigated demographics or pharmaceutical covariates (age, diabetes status, body mass index, or concomitant use of diuretics, proton pump inhibitors or H2-blockers) demonstrated statistically significant association with topiramate use and thus were not included as covariates.
Conclusion: Our results demonstrate that odds of a stone within the last 12 months is increased significantly with topiramate use. Additionally, we provide the initial quantification of the strength of this association, with an estimated 8-fold increase in odds of stone formation. These findings can provide physicians with important data and improve risk counseling for patients considering topiramate use.


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