Citrate salts for preventing and treating calcium containing kidney stones in adults

Kidney stones are one of the most common disorders of the urinary tract. They typically affect people aged 40 to 60 years of age and are twice as common in men than women although recent data suggest the risks are more equal. Calcium stones are the most common type of kidney stone and occur in two major forms: calcium oxalate and calcium phosphate. Kidney stones can cause severe abdominal pain and may require urgent treatment; they are one of the main causes of unscheduled admissions in urological practice.

Following treatment even first time stone formers have a risk for recurrence which increased with each subsequent stone. This increased risk of recurrence of stones is mainly attributed to altered composition of urine i.e. low citrate levels. Various prevention strategies including increased fluid intake and oral citrate supplements have been tried to modify the chemical composition of the urine. Citrate therapy is believed to stop crystals from growing into stones. The uncertainty of the true benefit of citrate therapy prompted this review.

We included seven studies (477 participants) in this review. Citrate salts significantly reduce stone size, prevent new stone formation, and results in stone size stability. People experienced more side effects, such as gastrointestinal disturbance, when using citrate salts than when using placebo, however the need for retreatment for stone removal was significantly less with citrate therapy.

Authors' 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.

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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.

Objectives: 

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.

Search strategy: 

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.

Selection criteria: 

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.

Data collection and analysis: 

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.

Main 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).

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