Potential thermodynamic and kinetic roles of phytate as an inhibitor of kidney stone formation: theoretical modelling and crystallization experiments
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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.
KeywordsSpeciation modelling Calcium–phytate complexation Urinary crystallization Aggregation inhibition Calcium stone formation
Major sections of the work described in this paper are based on studies performed by the first author Saajidah Fakier as part of her Ph.D. thesis . The authors wish to thank the South African National Research Foundation, the South African Medical Research Council and the University of Cape Town for financial support.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflicts of interest.
All procedures performed in human studies were approved by the Human Research Ethics Committee of the University of Cape Town (HREC REF: 072/2014) and were performed in accordance with the ethical standards of the 1964 Helsinki Declaration and its later amendments.
Informed consent was obtained from all individual participants included in the study.
- 11.Jappie D, Rodgers A (2000) Determination of the optimum number of subjects required for pooling urines: statistical approach. In: Rodgers AL, Hibbert BE, Hess B, Khan SR, Preminger GM (eds) Urolithiasis 2000 proc 9th Int Symp Urolithiasis, University of Cape Town, Cape Town, South Africa, pp 92Google Scholar
- 28.Hess B, Kok DJ (1983) Nucleation, growth and aggregation. In: Coe FL, Favus MJ, Pak CYC, Parks JH, Preminger G (eds) Kidney stones: medical and surgical management. Lippincott-Raven Publishers, Philadelphia, pp 3–32Google Scholar
- 30.Finlayson B (1974) Renal lithiasis in review. Urol Clin N Am 1:181–212Google Scholar
- 31.Rose GA (1987) Current trends in urolithiasis research. In: Rous N (ed) Stone disease: diagnosis and management. Grune & Stratton, Inc, Orlando, pp 383–416Google Scholar
- 33.Fakier S (2015) The effect of inositol-hexakisphosphate (phytate) on urinary risk factors for calcium oxalate urolithiasis in South African population groups with different kidney stone risk profiles: theoretical modelling, in vitro crystallisation experiments and in vivo human studies (Doctoral dissertation, University of Cape Town)Google Scholar