Medical treatment to prevent recurrent calcium urolithiasis. A guide to critical appraisal

Among patients with urolithiasis, the recurrence rate is 10-23% per year. We have applied guidelines for critical appraisal to 46 publications addressing the efficacy of thiazides, orthophosphates, cellulose phosphate, allopurinol, magnesium and citrate as prophylaxis against recurrent urolithiasis. The 34 studies which do not have a randomly allocated control group are subject to methodologic deficiencies such as co-intervention, variable outcome measures, variable natural history, statistical regression to the mean, selection bias and incomplete follow-up of patients. These deficiencies make conclusions regarding the efficacy of an intervention suspect. Among the 12 randomized clinical trials are 5 thiazide, 2 orthophosphate, 4 allopurinol and 1 magnesium intervention. The methodologic and statistical questions addressed were: adequacy of randomization, clinical relevance of outcomes, description of patients, clinical and statistical significance, and completeness of follow-up. Based on these methodologic considerations, one could not conclude that orthophosphates, cellulose phosphate, magnesium or citrate were efficacious in preventing recurrent urolithiasis. Two of the 5 thiazide and 1 of the 4 allopurinol randomized clinical trials demonstrate convincing evidence for efficacy of these interventions. With the exception of pilot studies of new interventions, conclusions about efficacy of interventions claimed to decrease the urolithiasis recurrence rate should be based on methodologically sound randomized clinical trials.