Hydrochlorothiazide does not alter kidney stone recurrence: NEJM

A new study published in the New England Journal Of Medicine suggests that the frequency of recurrence did not appear to differ significantly among patients with recurrent kidney stones who received hydrochlorothiazide once daily at doses of 12.5 mg, 25 mg, or 50 mg.

One of the most frequent disorders affecting the kidney is nephrolithiasis, which is distinguished by a high risk of recurrence. Although thiazide diuretic medications are frequently used to prevent kidney stones from recurring, there is insufficient evidence to support their superiority to a placebo in terms of effectiveness. Moreover, there are few dose-response data available. Consequently, in order to determine the effectiveness of hydrochlorothiazide in preventing kidney-stone recurrence, Nasser A. Dhayat and colleagues carried out this investigation.

Patients with recurrent calcium-containing kidney stones were randomly allocated to receive hydrochlorothiazide at a dosage of 12.5 mg, 25 mg, or 50 mg once a day or a placebo once daily in this double-blind experiment. Investigating the dose-response relationship for the main outcome, a composite of symptomatic or radiologic reappearance of kidney stones, was the major goal. The definition of radiologic recurrence was the development of new stones on imaging or the expansion of stones that were already present on the baseline picture. Also evaluated was safety.

The key findings of this study were:

416 patients were randomly assigned and monitored for a total of 2.9 years on average. 

60 of 102 patients (59%) in the placebo group, 62 of 105 patients (59%) in the hydrochlorothiazide group receiving 12.5 mg, 61 of 108 patients (56%) in the 25 mg group, and 49 of 101 patients (49%) in the 50 mg group experienced a main end-point event. 

A main end-point incident did not occur in response to the hydrochlorothiazide dosage (P=0.66). 

Those who took hydrochlorothiazide had a higher prevalence of hypokalemia, gout, new-onset diabetes, skin allergies, and a plasma creatinine level more than 150% of the baseline level than patients who got placebo.

Reference: 

Dhayat, N. A., Bonny, O., Roth, B., Christe, A., Ritter, A., Mohebbi, N., Faller, N., Pellegrini, L., Bedino, G., Venzin, R. M., Grosse, P., Hüsler, C., Koneth, I., Bucher, C., Del Giorno, R., Gabutti, L., Mayr, M., Odermatt, U., Buchkremer, F., … Fuster, D. G. (2023). Hydrochlorothiazide and Prevention of Kidney-Stone Recurrence. In New England Journal of Medicine (Vol. 388, Issue 9, pp. 781–791). Massachusetts Medical Society. https://doi.org/10.1056/nejmoa2209275