title: Citrate salts for preventing and treating calcium containing kidney stones in adults.
abstract: BACKGROUND
  Kidney stones affect people worldwide and have a high rate of recurrence even with treatment. Recurrences are particularly prevalent in people with low urinary citrate levels. These people have a higher incidence of calcium phosphate and calcium oxalate stones. Oral citrate therapy increases the urinary citrate levels, which in turn binds with calcium and inhibits the crystallisation thus reduces stone formation. Despite the widespread use of oral citrate therapy for prevention and treatment of calcium oxalate stones, the evidence to support its clinical efficacy remains uncertain.
  
  
  OBJECTIVE
  The objective of this review was to determine the efficacy and adverse events associated with citrate salts for the treatment and prevention of calcium containing kidney stones.
  
  
  METHODS
  We searched the Cochrane Kidney and Transplant Specialised Register to 29 July 2015 through contact with the Trials' Search Co-ordinator using search terms relevant to this review.
  
  
  METHODS
  We included randomised controlled trials (RCTs) that assessed the efficacy and adverse events associated with citrate salts for the treatment and prevention of calcium containing kidney stones in adults treated for a minimum of six months.
  
  
  METHODS
  Two authors assessed studies for inclusion in this review. Data were extracted according to predetermined criteria. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) and 95% CI for continuous outcomes.
  
  
  RESULTS
  We included seven studies that included a total of 477 participants, most of whom had oxalate stones. Of these, three studies (247 participants) compared potassium citrate with placebo or no intervention; three (166 participants) compared potassium-sodium citrate with no intervention; and one (64 participants) compared potassium-magnesium citrate with placebo. Overall, quality of the reporting of the included studies was considered moderate to poor, and there was a high risk of attrition bias in two studies.Compared with placebo or no intervention, citrate therapy significantly reduced the stone size (4 studies, 160 participants: RR 2.35, 95% CI 1.36 to 4.05). New stone formation was significantly lower with citrate therapy compared to control (7 studies, 324 participants: RR 0.26, 95% CI 0.10 to 0.68). The beneficial effect on stone size stability was also evident (4 studies, 160 participants: RR 1.97, 95% CI 1.19 to 3.26). Adverse events were reported in four studies, with the main side effects being upper gastrointestinal disturbance and one patient reported a rash. There were more gastrointestinal adverse events in the citrate group; however this was not significant (4 studies, 271 participants: RR 2.55, 95% CI 0.71 to 9.16). There were significantly more dropouts due to adverse events with citrate therapy compared to control (4 studies, 271 participants: RR 4.45, 95% CI 1.28 to 15.50). The need for retreatment was significantly less with citrate therapy compared to control (2 studies, 157 participants: RR 0.22, 95% CI 0.06 to 0.89).
  
  
  CONCLUSIONS
  Citrate salts prevent new stone formation and reduce further stone growth in patients with residual stones that predominantly contain oxalate. The quality of reported literature remains moderate to poor; hence a well-designed statistically powered multi-centre RCT is needed in order to answer relevant questions concerning the efficacy of citrate salts.
authors.affiliation: Department of Urology, Hull and East Yorkshire Hospitals NHS Trust, Castle Hill Hospital, Castle Rd, Cottingham, UK, HU16 5JQ.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Phillips
authors.forename: Vishwanath S
authors.initials: VS
authors.lastname: Hanchanale
authors.forename: Andy
authors.initials: A
authors.lastname: Myatt
authors.forename: Bhaskar
authors.initials: B
authors.lastname: Somani
authors.forename: Ghulam
authors.initials: G
authors.lastname: Nabi
authors.forename: C Shekhar
authors.initials: CS
authors.lastname: Biyani
mesh_terms: D000328:Adult; D002129:Calcium Oxalate; D002130:Calcium Phosphates; D002951:Citrates / Q000009:adverse effects / Q000627:therapeutic use* / Q000652:urine; D004338:Drug Combinations; D006801:Humans; D007669:Kidney Calculi / Q000737:chemistry* / Q000517:prevention & control / Q000628:therapy*; D017616:Magnesium Compounds / Q000627:therapeutic use; D017680:Potassium Compounds / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence; D055502:Secondary Prevention
chemical_list: D002130:Calcium Phosphates; D002951:Citrates; D004338:Drug Combinations; D017616:Magnesium Compounds; D017680:Potassium Compounds; D002129:Calcium Oxalate; C020243:calcium phosphate; C066902:potassium-magnesium citrate