Hydrochlorothiazide for Prevention of Kidney Stones
Hydrochlorothiazide is effective in preventing recurrent calcium kidney stones, particularly in patients with hypercalciuria, and should be offered as a pharmacological treatment option when increased fluid intake fails to prevent stone recurrence. 1
Mechanism of Action
- Hydrochlorothiazide reduces urinary calcium excretion, which is a key factor in calcium stone formation 1, 2
- The FDA-approved drug label confirms that hydrochlorothiazide "decreases the excretion of calcium," which contributes to its effectiveness in preventing kidney stones 2
- Beyond reducing urinary calcium, thiazides may also reduce urine oxalate excretion and increase urine zinc and magnesium, further contributing to stone prevention 3
Evidence for Effectiveness
- The American College of Physicians recommends thiazide diuretics as an effective pharmacological monotherapy for preventing recurrent nephrolithiasis when increased fluid intake alone is insufficient 1
- The American Urological Association specifically recommends thiazide diuretics for patients with high or relatively high urine calcium and recurrent calcium stones (Standard; Evidence Strength: Grade B) 1
- Traditional studies showed that hydrochlorothiazide can reduce stone progression in approximately 90% of patients with calcium stones 3
Dosing Considerations
- Thiazide dosages associated with a hypocalciuric effect include hydrochlorothiazide (25 mg orally, twice daily; 50 mg orally, once daily) 1
- Higher doses of thiazides were evaluated in most clinical trials (hydrochlorothiazide 50 mg, chlorthalidone 25 or 50 mg, indapamide 2.5 mg) 1
- Lower doses may be associated with fewer adverse effects, but their effectiveness compared to higher doses is less established 1
- A recent 2023 study found no significant dose-response relationship between hydrochlorothiazide (12.5 mg, 25 mg, or 50 mg once daily) and prevention of kidney stone recurrence, challenging earlier findings 4
Patient Selection
- Thiazides are most appropriate for patients with calcium stones, which are the most common type 1
- Particularly beneficial for patients with hypercalciuria, though they may be effective in normocalciuric patients as well 3
- Can be used for both calcium oxalate and calcium phosphate stone formers 1
Practical Considerations
- Dietary sodium restriction should be continued when thiazides are prescribed to maximize the hypocalciuric effect and limit potassium wasting 1
- Potassium supplementation (either potassium citrate or chloride) may be needed when thiazide therapy is employed 1
- Side effects requiring discontinuation occur in approximately 5-7% of patients 3, 5
- Potential side effects include hypokalemia, gout, new-onset diabetes mellitus, skin allergy, and elevated creatinine levels 4
Treatment Algorithm
- First-line approach: Increase fluid intake to achieve urine output of at least 2 liters per day 1, 6
- If stone formation persists despite adequate fluid intake, consider pharmacological therapy:
- For patients with multiple metabolic abnormalities or persistent stone formation, combination therapy may be necessary 7, 6
Monitoring
- Obtain a 24-hour urine specimen within six months of initiating treatment to assess response to therapy 7
- Monitor for side effects, particularly hypokalemia, which may require potassium supplementation 1
- Continue dietary modifications alongside pharmacological therapy for optimal results 1
Caveats and Pitfalls
- The therapeutic efficacy of thiazides cannot always be predicted by the degree of hypocalciuric response 3
- Inadequate fluid intake remains a major risk factor for stone recurrence regardless of pharmacological intervention 7, 6
- Dietary calcium restriction should be avoided as it can worsen stone formation 8, 6
- The 2023 NOSTONE trial challenges previous evidence, finding no significant difference in stone recurrence between hydrochlorothiazide (at doses of 12.5 mg, 25 mg, or 50 mg once daily) and placebo 4