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

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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.

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References

  1. Modlin M (1980) Urinary phosphorylated inositols and renal stone. Lancet 22:1113–1114

    Article  Google Scholar 

  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):885–891

    Article  Google Scholar 

  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 34:162–164

    Article  CAS  Google Scholar 

  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 12:2580–2587

    Article  CAS  Google Scholar 

  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 177:2366–2370

    Article  CAS  Google Scholar 

  6. Gans P, O’Sullivan B (2000) GLEE, a new computer program for glass electrode Calibration. Talanta 51:33–37

    Article  CAS  Google Scholar 

  7. Gans P, Sabatim A, Vacca A (1996) Investigation of equilibrium constants with the HYPERQUAD suite of programs. Talanta 43:1739–1753

    Article  CAS  Google Scholar 

  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 33:116–124

    Article  CAS  Google Scholar 

  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:s330

    Article  Google Scholar 

  10. May PM, Murray K (1991) JESS, a joint expert speciation system-1. Talanta 38:1409–1417

    Article  CAS  Google Scholar 

  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 92

  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 5:3016–3022

    Article  CAS  Google Scholar 

  13. Ryall RL, Hibberd CM, Marshall VR (1985) A method for studying inhibitory activity in whole urine. Urol Res 13:285–289

    Article  CAS  Google Scholar 

  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 23:231–238

    Article  CAS  Google Scholar 

  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 35:277–285

    Article  CAS  Google Scholar 

  16. Pak CYC, Ohata M, Holt K (1975) Effect of disphosphonate on crystallization of calcium Oxalate in vitro. Kidney Int 7:154–160

    Article  CAS  Google Scholar 

  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 99:828–840

    Article  CAS  Google Scholar 

  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 124:18–26

    Article  CAS  Google Scholar 

  19. Crea F, Stefano CD, Milea D, Sammartano S (2008) Formation and stability of phytate complexes in solution. Coord Chem Rev 252:1108–1120

    Article  CAS  Google Scholar 

  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 43:401–406

    Article  CAS  Google Scholar 

  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 376:1030–1040

    Article  CAS  Google Scholar 

  22. Evans WJ, McCourtney EJ, Shrager RI (1982) Titrations of phytic acid. JAOCS 59:189–191

    Article  CAS  Google Scholar 

  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 138:76–83

    Article  CAS  Google Scholar 

  24. Grases F, Kroupa M, Costa-Bauza A (1994) Studies on calcium oxalate monohydrate crystallization: influence of inhibitors. Urol Res 22:39–43

    Article  CAS  Google Scholar 

  25. Grases F, March P (1989) A study about some phosphate derivatives as inhibitors of calcium oxalate growth. J Cryst Growth 96:993–995

    Article  CAS  Google Scholar 

  26. Kavanagh JP (2006) In vitro calcium oxalate crystallisation methods. Urol Res 34:139–145

    Article  CAS  Google Scholar 

  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 40:220–230

    Article  CAS  Google 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 3–32

    Google Scholar 

  29. Finlayson B (1978) Physicochemical aspects of uroliths. Kidney Int 13:344–360

    Article  CAS  Google Scholar 

  30. Finlayson B (1974) Renal lithiasis in review. Urol Clin N Am 1:181–212

    CAS  Google Scholar 

  31. Rose GA (1987) Current trends in urolithiasis research. In: Rous N (ed) Stone disease: diagnosis and management. Grune & Stratton, Inc, Orlando, pp 383–416

    Google Scholar 

  32. Saied N, Aider M (2014) Zeta potential and turbidimetry analyzes for the evaluation of chitosan/phytic acid complex formation. J Food Res 3:71–81

    Article  CAS  Google 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)

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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.

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  1. 1Department of Chemistry, University of Cape Town, Rondebosch, Private Bag, Cape Town, 7701, South Africa

    Saajidah Fakier, Allen Rodgers & Graham Jackson

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  1. Saajidah Fakier
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  2. Allen Rodgers
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  3. Graham Jackson
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Correspondence to Allen Rodgers.

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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.

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Fakier, S., Rodgers, A. & Jackson, G. Potential thermodynamic and kinetic roles of phytate as an inhibitor of kidney stone formation: theoretical modelling and crystallization experiments. Urolithiasis 47, 493–502 (2019). https://doi.org/10.1007/s00240-019-01117-1

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  • DOI: https://doi.org/10.1007/s00240-019-01117-1

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