Background: Nephrolithiasis 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.


Methods: In 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.

在此项双盲试验中,我们将复发性含钙肾结石患者随机分成4组,分别接受每日一次,每次12.5 mg、25 mg或50 mg氢氯噻嗪或每日一次安慰剂。主要目的是研究主要终点(由有症状肾结石复发或影像学肾结石复发构成的复合结局)的剂量-反应关系。影像学复发的定义为影像上出现新发结石或基线图像上观察到的原有结石增大。本试验还评估了安全性。

Results: In 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.

共计416例患者被随机分组并接受中位2.9年随访。安慰剂组102例患者中的60例(59%)、12.5 mg氢氯噻嗪组105例患者中的62例(59%)(与安慰剂相比的率比,1.33;95%置信区间[CI],0.92~1.93)、25 mg组108例患者中的61例(56%)(率比,1.24;95% CI,0.86~1.79)和50 mg组101例患者中的49例(49%)(率比,0.92;95% CI,0.63~1.36)发生了主要终点事件。氢氯噻嗪剂量与主要终点事件发生情况无关(P=0.66)。氢氯噻嗪组以下事件的发生率高于安慰剂组:低钾血症、痛风、新发糖尿病、皮肤过敏和血浆肌酐水平超过基线水平的150%。

Conclusions: Among 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 number, NCT03057431.). 

在复发性肾结石患者中,接受每日一次,每次12.5 mg、25 mg或50 mg氢氯噻嗪或每日一次安慰剂患者的复发率似乎无明显差异。(由瑞士国家科学基金会[Swiss National Science Foundation]和Inselspital资助;NOSTONE在ClinicalTrials.gov注册号为NCT03057431。)


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