Topiramate and Zonisamide Linked to Increased Risk of Symptomatic Kidney Stones, suggests study

A new study published in the American Journal of Kidney Diseases showed that Topiramate and zonisamide, which are often taken for obesity, epilepsy, and migraines, may increase the risk of kidney stones.

General practitioners are increasingly using topiramate and zonisamide, which were first created as antiseizure drugs, for various purposes including managing weight or preventing migraines. Although there is a paucity of empirical evidence supporting this link, topiramate and zonisamide may both contribute to kidney stone development by raising urine pH and lowering urine citrate. Thus, this study by Bassel Salka and colleagues investigated the association between kidney stone risk and the usage of topiramate and zonisamide.

Age- and sex-matched controls were chosen for this retrospective cohort study, which included Medicare enrollees and people in Optum's deidentified Clinformatics Data Mart Database (CDM) who had at least one prescription filled for topiramate or zonisamide between January 1, 2011, and September 30, 2019.

The exposure criteria were either new usage of zonisamide or topiramate. The main outcome was determined to be a symptomatic stone occurrence, which is defined as a visit to the emergency room, hospitalization, or kidney stone surgery. The primary analytical method was Cox proportional hazards regression.

During the trial period, 187,032 out of 1,122,301 patients completed prescriptions for either zonisamide or topiramate. In the CDM and Medicare cohorts, the unadjusted cumulative incidence of symptomatic stone occurrences between 3 months and 3 years following the first filled prescription was 2.9% and 2.0% among topiramate or zonisamide users, respectively, when compared to 1.2% and 1.3% among nonusers (P<0.001 for each comparison).

The users were much more likely than nonusers to experience a symptomatic stone incident after adjusting for covariates (CDM cohort: HR, 1.58 [95% CI, 1.49-1.68]; Medicare cohort: HR, 1.22 [95% CI, 1.11-1.34]). Younger adults taking either topiramate or zonisamide had a larger correlation with stone risk, and higher dosages of topiramate increased the likelihood of a symptomatic stone occurrence.

Overall, an elevated risk of symptomatic stone events was linked to the use of topiramate or zonisamide. Various results help weigh the advantages and disadvantages of various drugs. Potential bias in unmeasured variations among topiramate or zonisamide users and nonusers was the study's main weakness. 

Reference:

Salka, B. R., Oerline, M. K., Yan, P., Hsi, R. S., Crivelli, J. J., Asplin, J. R., Shahinian, V. B., & Hollingsworth, J. M. (2025). Associations of topiramate and zonisamide use with kidney stones: A retrospective cohort study. American Journal of Kidney Diseases: The Official Journal of the National Kidney Foundation, 85(6), 687-694.e1. https://doi.org/10.1053/j.ajkd.2024.12.009