Clinical Question

Do citrate salts treat and prevent calcium-containing kidney stones in adults?

Evidence-Based Answer

Citrate supplementation reduces stone size to less than 5 mm and prevents new stone formation when compared with placebo or no intervention. Citrate therapy also stabilizes existing stones and decreases the need for retreatment. These benefits come at the expense of upper gastrointestinal disturbances that lead to a higher dropout rate.¹ (Strength of Recommendation: B, based on inconsistent or limited-quality patient-oriented evidence.)

Practice Pointers

In the United States, the prevalence of symptomatic kidney stones is 8.8% in the general population, and is higher in men (10.6%) and obese individuals (11.2%).² Without prevention, 10% of individuals will have a symptomatic recurrence of stones at one year, 33% at five years, 50% at 10 years, and 75% at 20 years.³ Urinary tract stones represent an important health care expense with charges exceeding $10 billion annually in the United States.³ Because citrate binds urinary calcium, it may inhibit the formation of calcium oxalate stones; therefore, the authors of this Cochrane review aimed to determine if the use of citrate salts can prevent and treat calcium-containing kidney stones.

This Cochrane review included seven randomized controlled trials with a total of 477 participants.¹ Three studies compared potassium citrate supplementation with placebo or no intervention, and three studies compared potassium-sodium citrate with no intervention. One study compared potassium-magnesium citrate with placebo. Primary outcomes included radiographic evidence (plain radiography, computed tomography, or intravenous urography) of reduced stone size to less than 5 mm, lack of new stone formation, or stone size stability over six months, one year, or two years. Secondary outcomes were the need for retreatment, adverse events, and dropout rates. Dosages of citrate therapy ranged from 30 to 60 mEq per day.

Citrate therapy increased the likelihood of stone size reduction to less than 5 mm (relative risk [RR] = 2.35; 95% confidence interval [CI], 1.36 to 4.05). The incidence of new stone formation over a period of 12 to 48 months was also significantly reduced (RR = 0.26; 95% CI, 0.10 to 0.68). Citrate therapy prevented growth of existing stones (RR = 1.97; 95% CI, 1.19 to 3.26). Only two studies reported the need for retreatment as an outcome; in these, citrate therapy significantly decreased the need for retreatment vs. control (RR = 0.22; 95% CI, 0.06 to 0.89) over a follow-up period of three to four years. In absolute terms, the need for retreatment was 3.6% vs. 41.4% in the first study⁴ and 8% vs. 22% in the second.⁵

Adverse events and dropout rates were higher in the citrate treatment groups. The most commonly reported adverse events with citrate treatment were upper gastrointestinal disturbance and rash, but these differences were not significant between the citrate and placebo groups. Although rates of adverse events did not significantly differ between groups, dropout rates because of adverse events were significantly higher in patients receiving citrate therapy (RR = 4.45; 95% CI, 1.28 to 15.50). Overall, dropout rates because of noncompliance were similar between the groups. Risk of bias was considered low. The individual studies did not provide enough information for the authors of this review to reach a conclusion regarding the most effective dose of citrate salts.

Current guidelines from the American College of Physicians recommend that patients with one or more previous kidney stone episodes increase their fluid intake to produce at least 2 L of urine per day.⁶ If increased fluid intake fails to prevent recurrent episodes, treatment with a thiazide diuretic, allopurinol, or citrate is recommended. These recommendations are based on moderate-quality evidence.⁶ The results of this Cochrane review support the recommendations in the American College of Physicians guidelines.

The practice recommendations in this activity are available at http://www.cochrane.org/CD010057.