Meta-analysis of randomized trials for medical prevention of calcium oxalate nephrolithiasis

Objectives: To determine the efficacy of commonly used medications in comparison with placebo or no treatment for the prevention of renal stone recurrence (metaphylaxis) as documented in the literature. Methods: A MEDLINE search identified 14 randomized, controlled trials comprising 20 treatment arms and 6 different drug therapies for the prevention of stone recurrence. The active treatment arms from each of the trials were combined, and the results were compared with those of the control or no treatment arms overall and for each category of drug therapy (thiazide diuretics, allopurinol, phosphate, magnesium, and alkali citrate). A meta-analysis was performed of the combined treatment and control arms for all trials from which sufficient data were provided, both for overall medical therapy and for thiazide treatment. Results: A statistically significant benefit of drug therapy for stone metaphylaxis was identified (P = 0.04), largely because of the benefit of thiazides compared with placebo or no treatment (P = 0.02). Allopurinol conferred no overall benefit, although the only trial evaluating therapy in hyperuricosuric patients showed a statistically significant benefit. Conclusion: Medical therapy for calcium stone disease reduces the incidence of recurrence. Although only thiazide diuretics among the drug therapies were shown to significantly reduce stone recurrence, variability in study design and study population precluded adequate analysis of other drug therapies such as alkali citrate. Standardization of study design and reporting should improve the evaluation of the efficacy of new drug treatments.