Prior studies have shown that thiazide diuretics' ability to decrease symptomatic stone events depends on the extent to which they reduce urine calcium. However, it remains unknown whether the calcium change from thiazide diuretics depends on the baseline urine calcium level.
Among a cohort of Medicare beneficiaries with a 24-hour urine collection for kidney stone disease processed by Labcorp/Litholink between 2011-2018, we identified a subset aged >18 years newly prescribed a thiazide diuretic who performed a second collection between 30 and 180 days after their initial prescription fill. We then fit multivariable linear regression models to estimate the association between dose of thiazide prescribed and change in urine calcium, stratifying by baseline urine calcium. We compared cumulative incidences of clinical stone events stratified by baseline urine calcium groups within a treated and untreated cohort.
From a total of 634 participants, higher baseline urine calcium was associated with greater 24-hour mean absolute (in mg/d) and percentage urine calcium reductions (Ptrend<0.001 for both). Higher thiazide dose was associated with greater absolute and percentage urine calcium reduction. No statistically significant differences were seen comparing the adjusted incidences of clinical stone events across baseline calcium groups after thiazide prescription. However, among individuals without thiazide exposure, the unadjusted and adjusted cumulative incidences were higher with greater baseline urine calcium (both Ptrend<0.001).
Greater urine calcium reductions after thiazide treatment are observed among those with higher baseline urine calcium, and higher thiazide dose led to a larger reduction. These data are relevant for individualizing thiazide dose for kidney stone prevention.
The Journal of urology. 2026 Mar 27 [Epub ahead of print]
Ryan S Hsi, Phyllis L Yan, Joseph J Crivelli, Pietro Manuel Ferraro, Gary C Curhan, Sarah Best, John R Asplin, Vahakn Shahinian, John M Hollingsworth
Department of Urology, Vanderbilt University Medical Center., Dow Division of Health Services Research, Department of Urology, University of Michigan., Department of Urology, University of Alabama at Birmingham School of Medicine., Section of Nephrology, Department of Medicine, Università degli studi di Verona, Verona, Italy., Channing Division of Network Medicine, Renal Division, Department of Medicine, Brigham and Women's Hospital., Department of Urology, University of Wisconsin, Madison, Wisconsin., Litholink Corporation, Laboratory Corporation of America Holdings®., Department of Urology, University of Florida College of Medicine, Gainesville.