Potential thermodynamic and kinetic roles of phytate as an inhibitor of kidney stone formation: theoretical modelling and crystallization experiments

Urolithiasis. 2019 Dec;47(6):493-502. doi: 10.1007/s00240-019-01117-1. Epub 2019 Feb 14.

Abstract

Kidney stone formation is governed by thermodynamic (supersaturation) and kinetic (crystal nucleation, growth, aggregation) mechanisms. We adopted a dual theoretical and experimental approach to investigate the potential role of urinary phytate in this regard. Thermodynamic constants for eight protonated phytate species and seven calcium-phytate complexes were determined by potentiometry and incorporated into the speciation program JESS. Urine was collected from 16 heathy males and their urine compositions were used as input for JESS. Phytate concentration was varied during modelling. No statistically significant decreases in Ca2+ concentrations or in supersaturation values were predicted by JESS. Crystallization experiments were then performed in pooled urine. Endogenous phytate concentration was determined using a metal-dye assay. The pool was dosed with various concentrations of phytate to achieve final concentrations equivalent to those used for modelling. Experiments showed that phytate had no effects on Ca2+ concentrations (as predicted by our theoretical modelling), metastable limits or crystal nucleation and growth kinetics. However, crystal aggregation kinetics was inhibited. We speculate that HPhy-11, small amounts of which were revealed by modelling, may bind to crystal surfaces and inhibit aggregation. We conclude that phytate exerts a kinetic, but not a thermodynamic inhibitory effect on crystallization in urine.

Keywords: Aggregation inhibition; Calcium stone formation; Calcium–phytate complexation; Speciation modelling; Urinary crystallization.

MeSH terms

  • Adolescent
  • Adult
  • Crystallization
  • Humans
  • Kidney Calculi / prevention & control*
  • Male
  • Models, Theoretical*
  • Phytic Acid / analysis
  • Phytic Acid / pharmacokinetics*
  • Phytic Acid / therapeutic use
  • Thermodynamics
  • Urine / chemistry
  • Young Adult

Substances

  • Phytic Acid