Medical management to prevent recurrent nephrolithiasis in adults: a systematic review for an American College of Physicians Clinical Guideline

Ann Intern Med. 2013 Apr 2;158(7):535-43. doi: 10.7326/0003-4819-158-7-201304020-00005.


Background: Optimum management to prevent recurrent kidney stones is uncertain.

Purpose: To evaluate the benefits and harms of interventions to prevent recurrent kidney stones.

Data sources: MEDLINE, Cochrane, and other databases through September 2012 and reference lists of systematic reviews and randomized, controlled trials (RCTs).

Study selection: 28 English-language RCTs that studied treatments to prevent recurrent kidney stones and reported stone outcomes.

Data extraction: One reviewer extracted data, a second checked accuracy, and 2 independently rated quality and graded strength of evidence.

Data synthesis: In patients with 1 past calcium stone, low-strength evidence showed that increased fluid intake halved recurrent composite stone risk compared with no treatment (relative risk [RR], 0.45 [95% CI, 0.24 to 0.84]). Low-strength evidence showed that reducing soft-drink consumption decreased recurrent symptomatic stone risk (RR, 0.83 [CI, 0.71 to 0.98]). In patients with multiple past calcium stones, most of whom were receiving increased fluid intake, moderate-strength evidence showed that thiazides (RR, 0.52 [CI, 0.39 to 0.69]), citrates (RR, 0.25 [CI, 0.14 to 0.44]), and allopurinol (RR, 0.59 [CI, 0.42 to 0.84]) each further reduced composite stone recurrence risk compared with placebo or control, although the benefit from allopurinol seemed limited to patients with baseline hyperuricemia or hyperuricosuria. Other baseline biochemistry measures did not allow prediction of treatment efficacy. Low-strength evidence showed that neither citrate nor allopurinol combined with thiazide was superior to thiazide alone. There were few withdrawals among patients with increased fluid intake, many among those with other dietary interventions and more among those who received thiazide and citrate than among control patients. Reporting of adverse events was poor.

Limitations: Most trial participants had idiopathic calcium stones. Nearly all studies reported a composite (including asymptomatic) stone recurrence outcome.

Conclusion: In patients with 1 past calcium stone, increased fluid intake reduced recurrence risk. In patients with multiple past calcium stones, addition of thiazide, citrate, or allopurinol further reduced risk.

Primary funding source: Agency for Healthcare Research and Quality.

Publication types

  • Research Support, N.I.H., Extramural
  • Review
  • Systematic Review

MeSH terms

  • Adult
  • Allopurinol / therapeutic use
  • Antimetabolites / therapeutic use
  • Carbonated Beverages
  • Citrates / therapeutic use
  • Drinking
  • Enzyme Inhibitors / therapeutic use
  • Fluid Therapy
  • Humans
  • Hydroxamic Acids / therapeutic use
  • Nephrolithiasis / diet therapy
  • Nephrolithiasis / drug therapy
  • Nephrolithiasis / prevention & control*
  • Practice Guidelines as Topic
  • Secondary Prevention
  • Thiazides / therapeutic use
  • Treatment Outcome


  • Antimetabolites
  • Citrates
  • Enzyme Inhibitors
  • Hydroxamic Acids
  • Thiazides
  • acetohydroxamic acid
  • Allopurinol