Citrate inhibits growth of residual fragments in an in vitro model of calcium oxalate renal stones

Background. Alkaline citrate is thought to be helpful in reducing recurrences of calcium oxalate stones. The evidence for this is incomplete, there have been few good trials, all with their own limitations, and not all reported any significant benefit. In vitro studies are usually cited to support the clinical studies but these too have their drawbacks, in particular they relate to crystals and microscopic aggregates and not to actual stone growth. Here we test citrate in vitro using a model of macroscopic calcium oxalate stone enlargement. Methods. Twelve calcium oxalate stones were grown at a time in a stone farm. Six were grown with 2 mmol/L citrate and six with 6 mmol/L citrate. Three protocols were tested; artificial urine, artificial urine with urinary macromolecules (UMM) from male controls and artificial urine with UMM front male stone formers. The stones were grown continuously for at least 24 days. Results. In all three experiments the higher citrate concentration significantly reduced the growth rate of stones by more than 50% (P < 0.001). There was a small decrease in ionised calcium in the stone growth media (P < 0.001) and significant (P < 0.001) but small increase in pH (about 0.07 pH units). The inclusion of UMM also brought about a decrease in stone growth, particularly at 2 mmol/L citrate. Conclusion. Citrate inhibited stone growth in this laboratory model. This was true both in defined media and with addition of UMM. This adds to evidence justifying the use of alkaline citrate in calcium oxalate nephrolithiasis.