We aimed to evaluate the effect and safety of thiazide diuretics on recurrent kidney calculi patients, comparing the incidence of recurrent kidney calculi and the 24-h urinary calcium level with that of placebo or no medication group in randomized controlled trials (RCTs). Therefore, we performed a systematic review and meta-analysis of clinical trials that investigated thiazide diuretics for the prevention of recurrent renal calculi to provide evidence-based medical data for use in clinical practice. Further, no meta-analyses have yet been conducted to prove that thiazide diuretics can prevent recurrent renal calculi. We also found that the recommended grade of thiazide diuretics to prevent recurrent kidney calculi was not consistent among guidelines. However, some clinical trials reported that thiazide diuretics had no significant prophylactic effect compared with the placebo. Among them, thiazide diuretics are the commonly used drugs for preventing recurrent kidney calculi.
In response to increasing incidence of kidney calculi, various interventions have been performed to prevent the occurrence of stones, including dietary interventions and medical treatments. Most kidney calculi are composed of calcium calcium oxalate stones are the most common, accounting for 74.8% of all cases of stones. Kidney calculi are caused by abnormal accumulation of some crystalline substances, such as calcium, oxalic acid, uric acid, and cystine, and organic matrices, such as matrix A and acid mucopolysaccharide, in the kidney. Correspondingly, the high recurrence rate yielded a certain economic burden to patients with kidney calculi. In the clinical guideline of the American College of Physicians, the prevalence of kidney calculi in men and women was 13% and 7%, respectively, and the 5-year recurrence rate of untreated kidney calculi was 35–50%. Kidney calculi are a common urinary system disease, and their incidence is increasing annually. Considering the adverse effects, poor patient compliance, and economic burden of long-term medication, their use in preventing recurrent kidney calculi is not recommended. However, the benefits are insufficient, and the evidence quality is low. Long-term use of thiazide diuretics reduces the incidence of recurrent renal calculi and 24-h urinary calcium level. The subgroup and sensitivity analysis findings were robust. The overall strength of recommendation for prevention of recurrent renal calculi using thiazide diuretics was not recommended. The evidence quality for decrease in kidney calculus incidence using thiazide diuretics was low, while that for the 24-h urinary calcium level decrease among those with recurrent kidney calculi was moderate, and that for the decrease in kidney calculus incidence using short-acting and long-acting thiazide diuretics was low. The thiazide diuretic groups had a high incidence of adverse reactions and low tolerance.
The pooled RR for the incidence of kidney calculi in the thiazide diuretic groups was 0.44 (95% CI 0.33–0.58, P < 0.0001) compared to that in the placebo and untreated groups the pooled RD was − 0.23 (95% CI − 0.30 to − 0.16, P < 0.0001). ResultsĮight RCTs involving 571 patients were included. The evidence quality was graded using the GRADE criteria, and recommendations for recurrent kidney calculus prevention using thiazide diuretics were reassessed. The pooled risk ratio (RR), risk difference (RD), standardized mean difference (SMD), and 95% confidence interval (CI) were calculated. The primary outcome was the incidence of recurrent kidney calculi, and the secondary outcome was the 24-h urinary calcium level. The PubMed, Cochrane Library, and EMBASE databases were systematically searched using the keywords thiazide diuretics and kidney calculi to identify randomized controlled trials (RCTs). We aimed to evaluate the effect and safety of thiazide diuretics on recurrent kidney calculi. However, whether thiazide diuretics can definitely prevent recurrent kidney calculi remains unclear. Thiazide diuretics reduce the risk of recurrent kidney calculi in patients with kidney calculi or hypercalciuria.
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