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Kidney Stones

Do I need to take medication to stop kidney stones coming back?

The drug most often prescribed for this failed its placebo-controlled trial. What replaces it is a test, not another tablet.

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Answer

Not automatically. In the NOSTONE trial, 416 patients with recurrent calcium stones took hydrochlorothiazide at 12.5, 25 or 50 mg daily or placebo for a median of 2.9 years, and recurrence was 59, 56, 49 and 59 percent respectively, with no dose-response and more side effects on the drug.

Key takeaways

  • NOSTONE randomised 416 patients with recurrent calcium-containing kidney stones to hydrochlorothiazide 12.5 mg, 25 mg or 50 mg daily or to placebo, with a median follow-up of 2.9 years.
  • Recurrence occurred in 59 percent on placebo, 59 percent on 12.5 mg, 56 percent on 25 mg and 49 percent on 50 mg, with no relation between dose and recurrence (P = 0.66).
  • Hypokalaemia, gout, new-onset diabetes, skin allergy and a plasma creatinine above 150 percent of baseline were all more common on hydrochlorothiazide than on placebo.
  • A 2025 network meta-analysis of nine trials in 999 patients concluded that thiazide and thiazide-like diuretics should not be routinely prescribed for stone prevention on current evidence.
  • A 2026 study of 634 patients found thiazides lower urine calcium most in those whose baseline urine calcium is highest, which is an argument for measuring it before prescribing.
  • The 2024 European Association of Urology guideline still recommends general measures — adequate fluid and calcium intake, low sodium and low protein — for every stone patient.

Thiazide diuretics have been the standard medical answer to recurrent calcium stones for decades. They lower urine calcium, urine calcium drives calcium stones, and the logic was strong enough that guidelines recommended them on evidence nobody called good. In 2023 the missing trial was run.

What the trial found

NOSTONE, published in the New England Journal of Medicine, randomised 416 patients with recurrent calcium-containing kidney stones, double-blind, to three doses of hydrochlorothiazide or to placebo, and followed them for a median of 2.9 years. The primary end point was symptomatic or radiologic recurrence.

NOSTONE: recurrence by group
GroupRecurredRate
Placebo60 of 10259%
Hydrochlorothiazide 12.5 mg62 of 10559%
Hydrochlorothiazide 25 mg61 of 10856%
Hydrochlorothiazide 50 mg49 of 10149%

The trial was built around a dose-response question and there was no dose-response, with a P value of 0.66. And the drug was not free of cost: hypokalaemia, gout, new-onset diabetes, skin allergy and a rise in creatinine above 150 percent of baseline were each more common on hydrochlorothiazide than on placebo.

What has been argued since

A 2025 network meta-analysis of nine trials in 999 patients found three regimens that did separate from placebo, but no dose-dependence and serious limitations, and concluded that these drugs should not be routinely prescribed for stone prevention.

The counter-argument is about selection rather than about the drug. If thiazides work by lowering urine calcium, a trial that enrols recurrent stone formers regardless of their urine calcium is testing the drug partly on people it was never expected to help. A 2026 analysis of 634 patients with paired 24-hour urine collections showed the biochemical half of that argument: the higher a patient's baseline urine calcium, the more a thiazide lowered it. It did not show the clinical half.

What this means in practice

A thiazide is not a proven way to stop calcium stones returning, and it should not be started as a default. It remains a reasonable option in a patient with genuinely high urine calcium who has been told about the risks of low potassium, gout and raised blood sugar.

The general measures the European Association of Urology recommends for every stone patient were not what NOSTONE tested and are not affected by its result: adequate fluid intake, adequate — not reduced — calcium intake, and low consumption of sodium and protein.

Sources

  1. 1

    Dhayat NA, Bonny O, Roth B, Christe A, Ritter A, Mohebbi N, Faller N, Pellegrini L, et al.

    Hydrochlorothiazide and prevention of kidney-stone recurrence

    New England Journal of Medicine 2023;388(9):781-791

    doi:10.1056/nejmoa2209275 · PMID:36856614

    https://doi.org/10.1056/nejmoa2209275
  2. 2

    Oliveira AV, Sampaio ALN, Mascarenhas RW, Pinto LOAD, Andriolo RB

    Thiazide and thiazide-like diuretics for kidney stones recurrence: a systematic review and network meta-analysis of randomised controlled trials

    World Journal of Urology 2025;44(1):41

    doi:10.1007/s00345-025-06137-8 · PMID:41396435

    https://doi.org/10.1007/s00345-025-06137-8
  3. 3

    Hsi RS, Yan PL, Crivelli JJ, Ferraro PM, Curhan GC, Best S, Asplin JR, Shahinian V, et al.

    Baseline urinary calcium and the efficacy of thiazide diuretics for kidney stone prevention

    Journal of Urology 2026;216(2):230-240

    doi:10.1097/ju.0000000000005042 · PMID:41894644

    https://doi.org/10.1097/ju.0000000000005042
  4. 4

    Skolarikos A, Somani B, Neisius A, Jung H, Petřík A, Tailly T, Davis N, Tzelves L, et al.

    Metabolic evaluation and recurrence prevention for urinary stone patients: an EAU guidelines update

    European Urology 2024;86(4):343-363

    doi:10.1016/j.eururo.2024.05.029 · PMID:39069389

    https://doi.org/10.1016/j.eururo.2024.05.029