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Urolithiasis

, Volume 47, Issue 6, pp 493–502 | Cite as

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

  • Saajidah Fakier
  • Allen RodgersEmail author
  • Graham Jackson
Original Paper
  • 84 Downloads

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

Speciation modelling Calcium–phytate complexation Urinary crystallization Aggregation inhibition Calcium stone formation 

Notes

Acknowledgements

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 [33]. 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.

Ethical approval

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

Informed consent was obtained from all individual participants included in the study.

Supplementary material

240_2019_1117_MOESM1_ESM.docx (17 kb)
Supplementary material 1 (DOCX 17 KB)
240_2019_1117_MOESM2_ESM.docx (14 kb)
Supplementary material 2 (DOCX 13 KB)

References

  1. 1.
    Modlin M (1980) Urinary phosphorylated inositols and renal stone. Lancet 22:1113–1114CrossRefGoogle Scholar
  2. 2.
    Curhan GC, Willett WC, Knight EL, Stampfer MJ (2004) Dietary factors and the risk of incident kidney stones in younger women: Nurses’ Health Study II. Arch Int Med 164(8):885–891CrossRefGoogle Scholar
  3. 3.
    Grases F, March JG, Prieto RM, Simonet BM (2000) Urinary phytate in calcium oxalate stone formers and healthy people-dietary effects on phytate excretion. Scand J Urol Nephrol 34:162–164CrossRefGoogle Scholar
  4. 4.
    Grases F, Isern B, Sanchis P, Perello J, Torres JJ, Costa-Bauza A (2007) Phytate acts as an inhibitor in formation of renal calculi. Front Biosci 12:2580–2587CrossRefGoogle Scholar
  5. 5.
    Saw NK, Chow K, Rao PN, Kavanagh JP (2007) Effects of inositol hexaphosphate (phytate) on calcium binding, calcium oxalate crystallization and in vitro stone growth. J Urol 177:2366–2370CrossRefGoogle Scholar
  6. 6.
    Gans P, O’Sullivan B (2000) GLEE, a new computer program for glass electrode Calibration. Talanta 51:33–37CrossRefGoogle Scholar
  7. 7.
    Gans P, Sabatim A, Vacca A (1996) Investigation of equilibrium constants with the HYPERQUAD suite of programs. Talanta 43:1739–1753CrossRefGoogle Scholar
  8. 8.
    Allie-Hamdulay S, Rodgers A (2005) Prophylactic and therapeutic properties of a sodium citrate preparation in the management of calcium oxalate urolthiasis: randomized, placebo-controlled trial. Urol Res 33:116–124CrossRefGoogle Scholar
  9. 9.
    Schlemmer U, Frolich W, Prieto RM, Grases F (2009) Phytate in foods and significance in humans: food sources, intake, processing, bioavailability, protective role and analysis. Mol Nutr Food Res 53:s330CrossRefGoogle Scholar
  10. 10.
    May PM, Murray K (1991) JESS, a joint expert speciation system-1. Talanta 38:1409–1417CrossRefGoogle Scholar
  11. 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
  12. 12.
    Costa-Bauza A, Grases F, Fakier S, Rodriguez A (2013) A novel metal-dye system for urinary phytate detection at micro-molar levels in rats. Anal Methods 5:3016–3022CrossRefGoogle Scholar
  13. 13.
    Ryall RL, Hibberd CM, Marshall VR (1985) A method for studying inhibitory activity in whole urine. Urol Res 13:285–289CrossRefGoogle Scholar
  14. 14.
    Hess B, Meinhardt U, Zipperle L, Giovanoli R, Jaeger P (1995) Simultaneous measurement of calcium oxalate crystal nucleation and aggregation: impact of various modifiers. Urol Res 23:231–238CrossRefGoogle Scholar
  15. 15.
    Webber D, Rodgers AL, Sturrock ED (2007) Glycosylation of prothrombin fragment 1 Governs calcium oxalate crystal nucleation and aggregation, but not crystal growth. Urol Res 35:277–285CrossRefGoogle Scholar
  16. 16.
    Pak CYC, Ohata M, Holt K (1975) Effect of disphosphonate on crystallization of calcium Oxalate in vitro. Kidney Int 7:154–160CrossRefGoogle Scholar
  17. 17.
    Torres J, Dominguez S, Cerda MF, Obal G, Mederos A, Irvine RF et al (2005) Solution behaviour of myo-inositol hexakisphosphate in the presence of multivalent cations. Prediction of a neutral pentamagnesium species under cytosolic/nuclear conditions. J Inorg Biochem 99:828–840CrossRefGoogle Scholar
  18. 18.
    Crea P, de Robertis A, de Stefano C, Sammartano S (2006) Speciation of phytate ion in aqueous solution. Sequestration of magnesium and calcium by phytate at different temperatures and ionic strengths, in NaCl. Biophys Chem 124:18–26CrossRefGoogle Scholar
  19. 19.
    Crea F, Stefano CD, Milea D, Sammartano S (2008) Formation and stability of phytate complexes in solution. Coord Chem Rev 252:1108–1120CrossRefGoogle Scholar
  20. 20.
    Li N, Wahlberg O (1989) Equilibrium constants of phytate ions. 2. Equilibrium between phytateions, sodium ions and protons in sodium perchlorate medium. Acta Chem Scand 43:401–406CrossRefGoogle Scholar
  21. 21.
    Stefano CD, Milea D, Pettignano A, Sammartano S (2003) Speciation of phytate ion in aqueous solution. Alkali metal complex formation in different ionic media. Anal Bioanal Chem 376:1030–1040CrossRefGoogle Scholar
  22. 22.
    Evans WJ, McCourtney EJ, Shrager RI (1982) Titrations of phytic acid. JAOCS 59:189–191CrossRefGoogle Scholar
  23. 23.
    Crea F, Crea P, Stefano CD, Milea D, Sammartano S (2008) Speciation of phytate ion in aqueous solution. Protonation in CSCl(aq) at different ionic strengths and mixing effects in LiCl(aq) + CsCl(aq). J Mol Liq 138:76–83CrossRefGoogle Scholar
  24. 24.
    Grases F, Kroupa M, Costa-Bauza A (1994) Studies on calcium oxalate monohydrate crystallization: influence of inhibitors. Urol Res 22:39–43CrossRefGoogle Scholar
  25. 25.
    Grases F, March P (1989) A study about some phosphate derivatives as inhibitors of calcium oxalate growth. J Cryst Growth 96:993–995CrossRefGoogle Scholar
  26. 26.
    Kavanagh JP (2006) In vitro calcium oxalate crystallisation methods. Urol Res 34:139–145CrossRefGoogle Scholar
  27. 27.
    Hess B, Ryall RL, Kavanagh JP, Khan SR, Kok D, Rodgers AL et al (2001) Methods for measuring crystallisation in urolithiasis research: why, how and when. Eur Urol 40:220–230CrossRefGoogle Scholar
  28. 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
  29. 29.
    Finlayson B (1978) Physicochemical aspects of uroliths. Kidney Int 13:344–360CrossRefGoogle Scholar
  30. 30.
    Finlayson B (1974) Renal lithiasis in review. Urol Clin N Am 1:181–212Google Scholar
  31. 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
  32. 32.
    Saied N, Aider M (2014) Zeta potential and turbidimetry analyzes for the evaluation of chitosan/phytic acid complex formation. J Food Res 3:71–81CrossRefGoogle Scholar
  33. 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

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.1Department of ChemistryUniversity of Cape TownCape TownSouth Africa

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