• Nasser A Dhayat, Olivier Bonny, Beat Roth, Andreas Christe, Alexander Ritter, Nilufar Mohebbi, Nicolas Faller, Lisa Pellegrini, Giulia Bedino, Reto M Venzin, Philipp Grosse, Carina Hüsler, Irene Koneth, Christian Bucher, Rosaria Del Giorno, Luca Gabutti, Michael Mayr, Urs Odermatt, Florian Buchkremer, Thomas Ernandez, Catherine Stoermann-Chopard, Daniel Teta, Bruno Vogt, Marie Roumet, Luca Tamò, Grazia M Cereghetti, Sven Trelle, and Daniel G Fuster.
• From the Departments of Nephrology and Hypertension (N.A.D., N.F., B.V., L.T., G.M.C., D.G.F.), Urology (B.R.), and Radiology (A.C.), Inselspital, Bern University Hospital, and CTU Bern (M.R., S.T.), University of Bern, Bern, Service of Nephrology, Lausanne University Hospital, University of Lausanne, Lausanne (O.B.), the Department of Nephrology, University Hospital Zurich, Zurich (A.R., N.M.), the Department of Nephrology, Regional Hospital Lugano (L.P., G.B.), and Università della Svizzera Italiana (R.D.G., L.G.), Lugano, the Department of Nephrology, Cantonal Hospital Graubünden, Chur (R.M.V., P.G.), the Department of Nephrology and Transplantation Medicine, Cantonal Hospital St. Gallen, St. Gallen (C.H., I.K., C.B.), the Department of Internal Medicine, Regional Hospital of Bellinzona, Bellinzona (R.D.G., L.G.), the Medical Outpatient Department, University Hospital Basel, University of Basel, Basel (M.M.), the Department of Nephrology, Luzerner Kantonsspital LUKS, Lucerne (U.O.), the Division of Nephrology, Dialysis, and Transplantation, Cantonal Hospital Aarau, Aarau (F.B.), the Department of Nephrology, University Hospital Geneva, University of Geneva, Geneva (T.E., C.S.-C.), and the Nephrology Service, Centre Hospitalier du Valais Romand, Sion (D.T.) - all in Switzerland.
• N. Engl. J. Med. 2023 Mar 2; 388 (9): 781791781-791.

BackgroundNephrolithiasis is one of the most common conditions affecting the kidney and is characterized by a high risk of recurrence. Thiazide diuretic agents are widely used for prevention of the recurrence of kidney stones, but data regarding the efficacy of such agents as compared with placebo are limited. Furthermore, dose-response data are also limited.MethodsIn this double-blind trial, we randomly assigned patients with recurrent calcium-containing kidney stones to receive hydrochlorothiazide at a dose of 12.5 mg, 25 mg, or 50 mg once daily or placebo once daily. The main objective was to investigate the dose-response effect for the primary end point, a composite of symptomatic or radiologic recurrence of kidney stones. Radiologic recurrence was defined as the appearance of new stones on imaging or the enlargement of preexisting stones that had been observed on the baseline image. Safety was also assessed.ResultsIn all, 416 patients underwent randomization and were followed for a median of 2.9 years. A primary end-point event occurred in 60 of 102 patients (59%) in the placebo group, in 62 of 105 patients (59%) in the 12.5-mg hydrochlorothiazide group (rate ratio vs. placebo, 1.33; 95% confidence interval [CI], 0.92 to 1.93), in 61 of 108 patients (56%) in the 25-mg group (rate ratio, 1.24; 95% CI, 0.86 to 1.79), and in 49 of 101 patients (49%) in the 50-mg group (rate ratio, 0.92; 95% CI, 0.63 to 1.36). There was no relation between the hydrochlorothiazide dose and the occurrence of a primary end-point event (P = 0.66). Hypokalemia, gout, new-onset diabetes mellitus, skin allergy, and a plasma creatinine level exceeding 150% of the baseline level were more common among patients who received hydrochlorothiazide than among those who received placebo.ConclusionsAmong patients with recurrent kidney stones, the incidence of recurrence did not appear to differ substantially among patients receiving hydrochlorothiazide once daily at a dose of 12.5 mg, 25 mg, or 50 mg or placebo once daily. (Funded by the Swiss National Science Foundation and Inselspital; NOSTONE ClinicalTrials.gov number, NCT03057431.).Copyright © 2023 Massachusetts Medical Society.

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