Urinary citrate is a potent endogenous inhibitor of stone formation [1, 2]. Hypocitraturia, variably defined by urinary citrate excretion <320–500 mg daily, is an important risk factor for the development of calcium kidney stones. The prevalence of hypocitraturia in different series is highly variable and ranges from approximately 20 to 60 % [3]. Citrate forms soluble complexes with calcium, decreasing the supersaturation of calcium oxalate [1]. Citrate has also been demonstrated to bind to the calcium oxalate crystal surface where it interferes with crystal growth and agglomeration [3].

Urinary citrate excretion is determined by multiple factors. The acid–base status of a particular individual has the strongest influence on urinary citrate excretion. Metabolic acidosis and dietary acid loads increase proximal tubular reabsorption of citrate, a potential base, leading to decreased urinary citrate excretion. Alkalemia induces the opposite effect, promoting increased citrate excretion. Most often hypocitraturia is idiopathic; however, certain medical conditions are associated with decreased citrate excretion. These disorders include distal renal tubular acidosis, hypokalemia, and gastrointestinal malabsorption due to bowel resection, bariatric surgery, and pancreatic insufficiency. Medications, including carbonic anhydrase inhibitors such as topiramate, are also associated with reduced citrate excretion.

Treatment with citrate preparations is one of the few evidence-based interventions proven to reduce recurring stones in patients with recurrent stone disease, particularly in stone formers with hypocitraturia [4, 5]. Citrate provides an alkali load which subsequently leads to increased urinary citrate excretion. Citrate therapy also increases urinary pH which is an important component of the treatment of uric acid and cystine stones. Prospective randomized controlled trials have evaluated the efficacy of various alkali citrate preparations for the prevention of recurrent calcium nephrolithiasis [6–8]. Treatment with potassium citrate and potassium–magnesium citrate therapy resulted in significant reductions in recurrent stone disease [7, 8]. However, Hofbauer and colleagues failed to show any significant reduction in recurrence in calcium stone formers treated with sodium-potassium citrate compared to matched controls [6]. This may be related to the effect of sodium to increase urinary calcium excretion. Potassium citrate has also been effective in patients who did not have hypocitraturia; it may therefore be appropriate when urine chemistries are relatively unremarkable or when other therapeutic options have not been effective.

Two prospective, randomized studies have shown significantly lower rates of stone recurrence and growth of residual stone fragments in patients treated with alkali citrate prophylaxis for 1 year after shock wave lithotripsy and/or percutaneous nephrolithotomy [9, 10]. A dramatic reduction in stone recurrence was demonstrated in one controlled study when subjects who were stone-free after lithotripsy received medical prophylaxis [9]. None of the subjects treated with potassium citrate 60 meq/day had recurrent stones after 12 months compared to 28.5 % in those who did not receive prophylactic treatment. Medically treated patients with residual stone fragments also had lower rates of stone growth compared to the untreated group [9]. Lojanapiwat et al. [10] studied the effect of sodium-potassium citrate on stone recurrence and regrowth after either shockwave lithotripsy or percutaneous nephrolithotomy in patients who were stone-free or had residual stone burden. After 12 months both stone-free status and unchanged stone size were significantly more frequent in the medical prophylaxis group compared to matched controls. For patients who were rendered stone-free, there was a 5.3-fold relative risk for recurrence in the control group compared to the medical prophylaxis group. Patients who had residual stone fragments were 1.38-fold more likely to have growth of their residual stones.