Increasing thiazide doses linked to fewer kidney stone events

Data recently published in JAMA Network Open show that increasing thiazide dosage was associated with greater reductions in urine calcium, which in turn correlated with fewer instances of symptomatic kidney stone events.¹

These findings may provide an explanation for results from the NOSTONE trial.

“What this means for patients is that thiazides remain an important option in the toolkit for preventing kidney stone recurrence. It may be beneficial to monitor calcium excretion while on thiazide therapy to adjust dose and diet to attain an adequate reduction in urine calcium,” said lead author Ryan S. Hsi, MD, FACS, in a news release on the findings.² Hsi is an associate professor in the department of urology at Vanderbilt University Medical Center in Nashville, Tennessee.

Overall, the study demonstrated that reductions in urine calcium were significantly associated with increasing doses of thiazide (P = .04 for absolute difference and P = .02 for percentage difference).

For patients who received a low dose of thiazide, the mean reduction in urine calcium was 79.3 mg/d (95% CI, −94.1 to −64.4 mg/d), correlating to a percentage reduction of 18.9% (95% CI, −23.9% to −14.0%). In the medium-dose cohort, the average reduction in urine calcium was 94.1 mg/d (95% CI, −106.7 to −81.5 mg/d), translating to a percentage reduction of 25.5% (95% CI, −29.6% to −21.3%). In the high-dose cohort, the average reduction in urine calcium was 104.6 mg/d (95% CI, −117.0 to −92.3 mg/d), correlating to a percentage reduction of 28.4% (95% CI, −32.6% to −24.4%).

Patients were then assigned to terciles based on the magnitude of urine calcium change following a thiazide prescription. A low change in urine calcium was an average reduction of 24 mg/d, the medium change was an average reduction of 90 mg/d, and the high change in urine calcium was an average reduction of 216 mg/d.

The cumulative incidence of a symptomatic stone event at 4 years was 28.8% (95% CI, 21.1%-35.7%) among patients in the low tercile for calcium change following thiazide prescription, 19.5% (95% CI, 12.9%-25.7%) among patients in the medium tercile for calcium change following a thiazide prescription, and 18.0% (95% CI, 11.5%-24.0%) among patients in the high tercile for calcium change following a thiazide prescription (P = .04).

In total, the current study included 634 adult participants with kidney stones who underwent initial 24-hour urine collection for stone risk assessment, were prescribed thiazides within 6 months following urine collection, and had follow-up collection between 30 and 180 days after their first prescription fill.

The average age of participants was approximately 68 years. Among all participants, 339 (53.5%) were men and 295 (46.5%) were women. Additionally, 602 (95.0%) were White, 12 were Black (1.9%), 2 (0.3%) were Asian, 2 (0.3%) were Hispanic, 2 (0.3%) were North American Native, 2 (0.3%) were of other races and ethnicities, and 12 (1.9%) were of unknown race and ethnicity.

According to the authors, these findings may provide an explanation for results from the NOSTONE trial (NCT03057431), which found that treatment with hydrochlorothiazide did not significantly reduce the incidence of kidney stone recurrence vs placebo.³ The calcium reductions observed in the current trial were greater than those observed in the NOSTONE trial, which ranged from reductions of 42 mg/d to 51 mg/d. Thus, the null finding, the authors explain, may have been due to calcium reductions that were insufficient to influence recurrence risk.

Based on findings from the current study, the investigators next plan to assess which subtypes and dosing of thiazides correlate to the greatest efficacy, as well as understand how to best optimize adherence to treatment, according to the news release.²

References

1. Hsi RS, Yan PL, Maalouf NM, et al. Thiazide dose, urine calcium, and symptomatic kidney stone events. JAMA Netw Open. 2024;7(8):e2428953.doi:10.1001/jamanetworkopen.2024.28953

2. Higher thiazide doses shown to reduce kidney stone events. News release. Vanderbilt University Medical Center. August 22, 2024. Accessed August 27, 2024. https://news.vumc.org/2024/08/22/higher-thiazide-doses-shown-to-reduce-kidney-stone-events/

3. Dhayat NA, Bonny O, Roth B, et al. Hydrochlorothiazide and prevention of kidney-stone recurrence. N Engl J Med. 2023;388(9):781-791.doi:10.1056/NEJMoa2209275