Thiazide Diuretic Dose and Risk of Kidney Stones in Older Adults: A Retrospective Cohort Study

Background: Thiazide diuretics are commonly prescribed to prevent kidney stones. However, it is unclear whether higher doses confer greater benefit. Objective: To determine whether lower doses of thiazide diuretics confer a similar protective effect against kidney stone events as higher doses. Design: Population-based cohort study. Setting: Linked health administrative databases in Ontario, Canada. Patients: Older adults newly prescribed a thiazide diuretic between 2003 and 2014 were separated into 2 groups based on daily dose: low dose (⩽12.5 mg hydrochlorothiazide/chlorthalidone, or ⩽1.25 mg indapamide) or high dose. Measurements: The primary outcome was time to a kidney stone event, using diagnosis and procedure codes. A secondary outcome was kidney stone surgery. Methods: An association between thiazide diuretic dose and a kidney stone event was estimated using Cox proportional hazards regression. Results: A total of 536 of 105 239 patients (0.51%) experienced a kidney stone event. We did not detect a difference in kidney stone risk in the high-dose relative to the low-dose group (adjusted hazard ratio, 1.10; 95% confidence interval, 0.93-1.31). Results were similar when analysis was restricted to the more specific outcome of kidney stone surgery. Neither a history of prior kidney stones nor the type of thiazide diuretic modified the effect of diuretic dose on outcome. Limitations: Patients were >65 years old and we were unable to adjust for some potential confounders such as dietary factors. Conclusions: Lower dose thiazide diuretics appear to confer a similar protective effect as higher dose thiazides against the development of kidney stones.