Medical expulsive therapy for pediatric urolithiasis: Systematic review and meta-analysis

Abstract

Kidney stone disease has become more common among children and young adults. Despite its well-documented success in adults, published success rates of medical expulsive therapy (MET) for pediatric urolithiasis vary widely. Our objective was to determine whether the aggregated evidence supports the use of MET in children. We searched the Cochrane Controlled Trials Register, clinicaltrials.gov, MEDLINE, and EMBASE databases, and recently presented meeting abstracts for reports in any language. In addition, the bibliographies of included studies were then hand-searched. The protocol was prospectively registered at PROSPERO (CRD42013005960). Inclusion criteria were children (aged≤18 years) with urolithiasis treated with medications with the specific goal of increasing spontaneous stone passage rate, including but not limited to alpha-adrenergic blockers (e.g., tamsulosin or doxazosin), calcium channel blockers (e.g., nifedipine), or other adjuvant medications (e.g., steroids or tolterodine). Manuscripts were then assessed and data abstracted in duplicate, with differences resolved by the senior author. Risk of bias was assessed using standardized instruments. Descriptive statistical analyses were performed as appropriate. We identified 11,197 studies, five of which (3 randomized controlled trials, 2 retrospective cohorts) were included in the pooled meta-analysis. Although we found little evidence of significant publication bias, we were unable to assess the likelihood of other forms of bias (allocation, selection) for most included studies due to reporting limitations. The pooled results demonstrate that MET significantly increased the odds of spontaneous stone passage (OR 2.21, 95% CI 1.40-3.49). Between-study heterogeneity was not statistically significant (I(2)=14%, p=0.36). Bivariate meta-regression models revealed no significant association between the likelihood of stone passage and study COI (p=0.9), study country (p=0.7), patient age (p=0.4), patient gender (p=0.4), duration of follow-up (p=0.3), or stone size (p=0.7). Side effects of MET were reported to be minimal. Relatively few patients reported any adverse effects at all; the most commonly reported issue was somnolence. Concerns about biases affecting the published outcomes of the included studies exist due to the low quality of the randomized controlled trials reviewed for analysis. However, there was little visual evidence of publication bias noted on the funnel plot, as confirmed by the Begg test (p=0.5). Consistent with the adult literature, pediatric studies demonstrate that treatment with MET results in increased odds of spontaneous ureteral stone passage and a low rate of adverse events. Although the accumulated literature is limited by inconsistent and/or incomplete reporting, there is nonetheless a clear, cumulative positive effect of MET on stone passage among children. The available evidence thus supports a prominent role for MET in treatment algorithms for pediatric urolithiasis.