Boosting Thiazide Dosage Can Reduce Kidney Stone Risk

TOPLINE:

Higher thiazide doses are linked to greater reductions in urine calcium levels, which correlate with fewer symptomatic kidney stone events. This association suggests that adjusting thiazide dosage could be crucial in kidney stone prevention.

METHODOLOGY:

• The efficacy of using thiazides for kidney stone prevention was called into question by the NOSTONE trial, which found no added benefit of hydrochlorothiazide over a placebo in preventing kidney stone recurrence in high-risk patients.
• Using the Medicare-Litholink Database, researchers identified adult participants with kidney stones prescribed thiazides (hydrochlorothiazide, chlorthalidone, or indapamide) within 6 months after initial 24-hour urine collection and who underwent follow-up urine collections between 30 and 180 days after their first thiazide prescription fill.
• Thiazide dosages were classified as:
  • Low (chlorthalidone, < 12.5 mg/d; indapamide, < 0.6125 mg/d; hydrochlorothiazide, < 25 mg/d)
  • Medium (chlorthalidone, 12.5 to < 25 mg/d; indapamide, 0.6125 to < 1.25 mg/d; hydrochlorothiazide, 25 to < 50 mg/d)
  • High (chlorthalidone, ≥ 25 mg/d; indapamide, ≥ 1.25 mg/d; hydrochlorothiazide, ≥ 50 mg/d)
• Changes in calcium levels in response to low, medium, and high thiazide dosages were evaluated. These changes were correlated with the incidence of symptomatic stone events, identified by emergency department visits, hospitalizations, or surgeries for stones within 6-48 months after the initial prescription fill.

TAKEAWAY:

• Researchers included 634 adults with kidney stones (mean age, 67.6 years; 46.5% women).
• Higher thiazide doses were associated with greater reductions in urine calcium levels, with a low dose resulting in an 18.9% reduction, a medium dose in a 25.5% reduction, and a high dose in a 28.4% reduction (P = .02).
• At 4 years, the adjusted cumulative incidence of symptomatic stone events was 28.8%, 19.5%, and 18.0% for a low, an intermediate, and a high tercile of change in urine calcium levels, respectively, after thiazide prescription (P = .04 for trend).

IN PRACTICE:

Considering the study’s findings, experts from the University of California, San Francisco, and other institutions wrote in an accompanying editorial that “clinicians need to first identify patients with hypercalciuria and then aggressively treat them with thiazide diuretics to yield the most benefit in reducing kidney stone recurrence,” adding, “However, most clinicians likely prefer to start at low dosages and then titrate the dosage based on adverse effects and efficacy.”

SOURCE:

This study was led by Ryan S. Hsi, MD, Department of Urology, Vanderbilt University Medical Center in Nashville, Tennessee. It was published online in JAMA Network Open.

LIMITATIONS:

This study’s limitations included the possibility of omitted variable bias and unmeasured differences between participants prescribed different dosages of thiazides. The sample consisted mostly of older adults, potentially limiting generalizability.

DISCLOSURES:

This study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health. The authors declared no conflicts of interests.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.