Is citrate an inhibitor of calcium oxalate crystal growth in high concentrations of urine?

Abstract

The effect of citrate on calcium oxalate (CaOx) crystal growth was studied in a system in which series of samples containing [45Ca]calcium chloride were brought to different levels of supersaturation with various concentrations of oxalate. The crystallization was assessed by measuring the amount of isotope remaining in solution 30 min after the addition of CaOx seed crystals to samples containing citrate in concentrations corresponding to those in final urine. The experiments were carried out both in pure salt solutions and in solutions with dialysed urine. Increased concentrations of citrate resulted in a reduced crystallization of CaOx in both the presence and absence of dialysed urine, but with the lowest rate of crystallization in the samples containing urine. The increased concentration of 45Ca remaining in solution reflected a reduced crystallization, which could possibly be explained both by a reduced supersaturation and by an increased inhibition of CaOx crystal growth. The direct effects of citrate on CaOx crystal growth were assessed by calculating the ion-activity product of CaOx (APCaOx) at corresponding degrees of crystallization. The APCaOx recorded at a 30% reduction of the amount of isotope in solution increased with increasing concentrations of citrate between 1.0 and 1.5 mmol/l samples both with and without dialysed urine. These findings indicate that citrate has a weak direct inhibitory effect on CaOx crystal growth, which adds to the reduced growth rate brought about by urinary macromolecules and a decreased supersaturation.

Endogenous oxalogenesis after acute intravenous loading with ethylene glycol or glycine in rats receiving standard and vitamin B6‐deficient diets

“…This process is influenced by the pH of the urine, the solute load, and the various inhibitors of crystallization 25 . Citrate is generally accepted to be an inhibitor of the nucleation of oxalate and calcium phosphate, 26–28 as well as inhibiting crystal aggregation 29,30 and stone growth 29,31 . Thus, hypocitraturia is an important risk factor for renal stone formation.…”

Induced urinary crystal formation as an analytical strategy for the prediction and monitoring of urolithiasis and other metabolism-related disorders

“…In fact, urolith formation is strongly influenced by a multitude of different substances [16-18], e.g. acid-rich urinary proteins [19], citrate [20,21], magnesium [22], osteopontin [23-25], Tamm-Horsfall protein [26-28], polycarboxylic acids [29,30], copolymers of polyacrylic acid [31], phosphonates [32] or even ‘unidentified biomacromolecules’ [33]. …”

Long-term Follow-up of Stone Formers Treated with a Low Dose of Sodium Potassium Citrate

“…The inhibition of CaOx crystal growth is most easily demonstrated in metastably supersaturated solutions, without urine or with urine in low concentrations. From recent crystallization experiments, it was concluded that there also was a small reduction in the rate of CaOx crystal growth in solutions with citrate concentrations corresponding to those in whole urine even in the presence of urinary macromoles (9). A powerful inhibition of CaOx along with CaP crystal aggregation has also been demonstrated (5,10).…”