Urinary components can both boost and impair crystallization

By Sally Robertson, B.Sc.Jul 10 2012

The prevention of renal stone formation with crystallization inhibitors somewhat depends on the joint effect of such compounds in the urine matrix, rather than on the individual action of each inhibitor, report researchers.

Interactions between these compounds can significantly modify their inhibitory behavior by producing either positive (synergistic) or negative effects.

Different urinary components such as citrate, magnesium, phytate, pyrophosphate, and glycosaminoglycans have been shown to inhibit crystallization.

"However, when those compounds are present in the urine, they are mixed with others and the effect of the possible interactions between the different compounds have been scarcely studied," explain Montserrat Lopéz-Mesas (Universitat Autònoma de Barcelona, Spain) and colleagues.

Using the urinary lithogenic risk test, the team assessed the inhibition of calcium oxalate crystallization by both individual and binary mixtures of its known inhibitors phytate, citrate, pyrophosphate, and chondroitin sulfate.

The researchers found that the maximum inhibition of calcium oxalate precipitation during the experiments was approximately 80-85%, with none of the assayed conditions achieving a total inhibition of precipitation.

As reported in Urology, the effects of phytate plus pyrophosphate and phytate plus citrate on calcium oxalate crystallization were different from the additive effects of the individual inhibitors.

The authors found that phytate, in concentrations ranging from 0.2-1.0 ppm was able to produce both significant synergistic effects on calcium oxalate precipitation in the presence of pyrophosphate (1.5 ppm) and significant negative effects in the presence of citrate (80 ppm).

For all other combinations of compounds, the differences between the binary and additive effects were not significant.

The team explains that synergistic effects occur when substances with high affinity for calcium (eg, a mixture of phytate and pyrophosphate), are selectively absorbed on active sites of calcium oxalate crystallization, disturbing the crystal surface more than would be expected simply through the additive effect of the individual inhibitors.

By contrast, negative effects occur when a substance with high affinity for calcium (eg, phytate) is in the presence of high amounts of another substance with low affinity (eg, citrate), causing the high affinity substance to be displaced from the active sites and therefore decreasing inhibition to below the additive effect.

"Because of the scarce knowledge of the interaction between compounds in the complex media of urine, further investigation in this concern will contribute to a better assessment on designing prophylactic treatments of urolithiasis based on inhibitors," concludes the team.

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