title: Herbal medicines for urinary stone treatment. A systematic review.
abstract: OBJECTIVE
  To analyze the clinical evidence on the efficacy of phytotherapy in the treatment of calculi in the urinary tract.
  
  
  METHODS
  To be eligible, full-length articles should include the results of randomized controlled trials enrolling patients affected by urolithiasis, reporting any comparison between an experimental herbal agent versus placebo or any active comparator, aimed at preventing the formation or facilitating the dissolution of calculi in any portion of the urinary tract. Fifteen databases were searched for relevant references. The primary outcomes investigated were (i) the reduction of stone size and/or number and (ii) the urinary excretion rates of calcium, urate, or oxalate. The secondary outcome of the review was the adverse effects (AE) of treatment. Risk of bias (ROB) and quality of the evidence were assessed according to Cochrane and GRADE guidelines. We performed a random-effect meta-analysis.
  
  
  RESULTS
  541 articles were retrieved and 16 studies were finally confirmed as eligible. Multiple Cochrane ROB tool items were rated as having high risk of bias in each analyzed trial report. Pooled analysis of continuous data could be performed for three different comparisons: (i) phytotherapy versus citrate as single agent (ii) phytotherapy versus placebo, (iii) preparation of Didymocarpus pedicellata (DP)--combined with other herbal agents--versus placebo. Results showed that citrate is superior to phytotherapy in significantly decreasing both the size of urinary stones (mean difference: phytotherapy, 0.42 mm higher; 95% CI: 0.23 to 0.6; Z = 4.42, P < 0.0001; I2 = 30%) and the urinary excretion rate of urate (mean difference: 42.32 mg/24h higher, 95% CI: 19.44 to 65.19; Z = 3.63, P = 0.0003; I2 = 96%), assessed after 3 months on-therapy. No significant differences in the excretion rates of urinary calcium or oxalate were found. The DP preparation was superior to placebo in inducing total clearance (risk ratio: 6.19, 95% CI: 2.60 to 14.74; Z = 4.12, P < 0.0001; I2 = 0%) and size reduction (mean difference: DP preparation, 4.93 mm lower; 95% CI: -9.18 to -0.67; Z = 2.27, P = 0.02; I2 = 99%) of renal and ureteral stones after 3 months of therapy. No significant differences in the inter-arm variation of excretion rates of urinary calcium or urate were found as result of the pooled phytotherapy-placebo comparison. Herbal remedies were in general devoid of side effects and in few cases citrate appeared to induce GI disturbances in a higher fraction of patients. Most reports did not provide inferential data concerning AE, and meta-analysis was not feasible.
  
  
  CONCLUSIONS
  Citrate is more effective than phytotherapy in decreasing the size of existing calculi in the urinary tract and in decreasing the urinary excretion rate of uric acid. A preparation containing Didymocarpus pedicellata combined with other herbal agents induces stone size reduction and clearance significantly better than placebo. Mayor limitations in the applicability of these results are the low quality of the evidence and the multiple sources of bias assessed in the studies included in the present review.
authors.affiliation: Department of Biotechnology and Life Sciences, Università degli Studi dell'Insubria, Busto Arsizio. elena.monti@uninsubria.it.
authors.forename: Elena
authors.initials: E
authors.lastname: Monti
authors.forename: Alberto
authors.initials: A
authors.lastname: Trinchieri
authors.forename: Vittorio
authors.initials: V
authors.lastname: Magri
authors.forename: Anne
authors.initials: A
authors.lastname: Cleves
authors.forename: Gianpaolo
authors.initials: G
authors.lastname: Perletti
mesh_terms: D002118:Calcium / Q000652:urine; D019343:Citric Acid / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D019815:Oxalic Acid / Q000652:urine; D008517:Phytotherapy / Q000379:methods; D028321:Plant Preparations / Q000009:adverse effects / Q000627:therapeutic use*; D010946:Plants, Medicinal / Q000737:chemistry*; D016032:Randomized Controlled Trials as Topic; D014527:Uric Acid / Q000652:urine; D014545:Urinary Calculi / Q000188:drug therapy* / Q000473:pathology
chemical_list: D028321:Plant Preparations; D014527:Uric Acid; D019343:Citric Acid; D019815:Oxalic Acid; D002118:Calcium