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A new approach to studying inhibitors of calcium oxalate crystal growth

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Summary

The nucleation and crystal growth of calcium oxalate (CaOx) were studied at pH 5.5 using turbidimetric measurements at 620 nm of suspensions produced by mixing calcium chloride and sodium oxalate (initial conditions: Ca, 3x10-3M; Ox, 0.5x10-3M). CaOx crystallization kinetics were defined first by the induction timet i and then by the slope of turbidity as a function of time during the interval corresponding to a correlation coefficientr 2>0.99. The technique described requires only a small amount of material, is quick, convenient, and can be used to study inhibitors of CaOx crystallization by comparingt i and the rate of crystal growth in the presence and absence of inhibitors. The effects on CaOx crystal growth of several low molecular weight compounds, i.e. di-and tricarboxylic acids, were examined. The majority of these compounds were inhibitors of crystal growth, the greatest effect being seen with citric acid (50% inhibition in the presence of 1.5x10-3M citric acid), isocitric acid (50% inhibition in the presence of 0.75x10-3M isocitric acid) and pyrophosphate (30% inhibition in presence of 0.15x10-3M pyrophosphate). The inhibitors' behaviour regarding the medium was studied without any assumptions about their possible mechanisms of action. Measurements of ionized calcium before and after the reaction, as well as the observation of crystals by scanning electron microspopy, allowed us to formulate the hypothesis that the effect of citric acid and tartaric acid can be attributed mainly to ion pairing, in contrast to that of pyrophosphate and the other carboxylic acids.

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References

  1. Achilles W (1987) Crystallization in gel matrices: a new experimental model of calcium stone formation. Contrib Nephrol 58:59

    PubMed  Google Scholar 

  2. Berg C, Tiselius HG (1986) The effect of pH on the risk of calcium oxalate crystallization in urine. Eur Urol 12:59

    PubMed  Google Scholar 

  3. Berg C, Larsson L, Tiselius HG (1990) Effects of different doses of alkaline citrate on urine composition and crystallization of calcium oxalate. Urol Res 18:13

    PubMed  Google Scholar 

  4. Berland Y, Olmer M, Boistelle R, Barlatier A (1984) Influence respective du calcium et de l'oxalate sur la cristallisation des oxalates de calcium dans l'urine. Nephrologie 5:175

    PubMed  Google Scholar 

  5. Boistelle R (1985) Concepts de la cristallisation en solution. Act Nephrol. Flammarion Medecine Sciences Ed: 159

  6. Cowley DM, McWhinney BC, Brown JM, Chalmers AH (1989) Effect on the urinary excretion of calcium and oxalate: relevance to calcium oxalate nephrolithiasis. Clin Chem 35:23

    PubMed  Google Scholar 

  7. Dezelic G, Dezelic N, Tezac BA (1963) A simple method for particle size determination by turbidity measurement. J Coll Sci 18:888

    Google Scholar 

  8. Fellström B, Backman U, Danielson BG, Holmgren K, Lunghall S, Wikström B (1982) Inhibitory activity of human urine on calcium oxalate crystal growth: effects of sodium urate and uric acid. Clin Sci 62:509

    PubMed  Google Scholar 

  9. Finlayson B (1978) Physicochemical aspects of urolithiasis. Kidney Int 13:344

    PubMed  Google Scholar 

  10. Gardner GL (1975) Nucleation and crystal growth of calcium oxalate trihydrate. Crystal Growth 30:158

    Google Scholar 

  11. Gardner GL, Doremus RH (1978) Crystal growth inhibitors in human urine: effect on calcium oxalate kinetics. Invest Urol 15:478

    PubMed  Google Scholar 

  12. Garti N, Tibika F, Sarig S, Perlberg S (1980) The inhibitory effect of polymeric carboxylic amino-acids and urine on calcium oxalate crystallization. Biochem Biophys Res Commun 97:1154

    PubMed  Google Scholar 

  13. Gill WB, Karesh IW, Garsin L, Roma MJ (1977) Inhibitory effects of urinary macromolecules on the crystallization of calcium oxalate. Invest Urol 15:95

    PubMed  Google Scholar 

  14. Grases F, Costa-Bauza A (1990) Study of factors affecting calcium oxalate crystalline aggregation. Br J Urol 66:240

    PubMed  Google Scholar 

  15. Hess, B, Nakagawa Y, Coe FL (1989) Inhibition of calcium oxalate monohydrate crystal aggregation by urine proteins. Am J Physiol 157:F99

    Google Scholar 

  16. Kok DJ, Papapoulos SE, blomen LJ, Bijvoet OLM (1988) Modulation of calcium oxalate monohydrate crystallization kinetics in vitro. Kidney Int 34:346

    PubMed  Google Scholar 

  17. Kohri K, Umekawa T, Kodama M, Katayama Y, Ishikawa Y, Takada M, Katoh Y, Kataoka K, Iguchi M, Kurita T (1990) Inhibitory effect of glutamic acid and aspartic acid on calcium oxalate crystal formation. Eur Urol 17:173

    PubMed  Google Scholar 

  18. Ligabue A, Fini M, Robertson WG (1979) Influence of urine on in vitro crystallization rate of calcium oxalate: Determination of inhibitory activity by a14C oxalate technique. Clin Chim Acta 98:39

    PubMed  Google Scholar 

  19. Lundager Madsen HE (1984) Aspects physicochimiques de la lithiase urinaire. Nephrologie 5:151

    PubMed  Google Scholar 

  20. Melik DH, Fogler HS (1983) Turbidimetric determination of particle size distributions of colloidal systems. J Coll Interf Sci 92:161

    Google Scholar 

  21. Meyer JL, Smith LH (1975) Growth of calcium oxalate crystals. II. Inhibition by natural urinary crystal growth inhibitors. Invest Urol 13:36

    PubMed  Google Scholar 

  22. Minero C, Maggiorotti P, Barbeni M, Pelizetti E, Tizzani A, Casseta G, Piana P, Giona C (1987) Effect of inhibitors on the crystal growth of calcium oxalate. Contrib Nephrol 58:65

    PubMed  Google Scholar 

  23. Pak CYC (1987) Citrate and renal calculi. Miner Electrolyte Metab 13:257–266

    PubMed  Google Scholar 

  24. Robertson WG, Peacock M, Marshall DH, Nordin BE (1976) Saturation-inhibition index as a measure of the risk of calcium oxalate stone formation in the urinary tract. N Engl J Med 294:249

    PubMed  Google Scholar 

  25. Scurr DS, Robertson WG (1986) Modifiers of calcium oxalate crystallization found in urine. III. Studies on the role of Tamm-Horsfall mucoprotein and of ionic strength. J Urol 136:505

    PubMed  Google Scholar 

  26. Sutor DJ (1969) Growth studies of calcium oxlate in the presence of various ions and compounds. Br J Urol 41:171

    PubMed  Google Scholar 

  27. Tiselius HG (1981) The effect of pH on the urinary inhibition of calcium oxalate crystal growth. Br J Urol 53:470

    PubMed  Google Scholar 

  28. Werness PG, Bergert JH, Lee EK (1981) Urinary crystal growth: effect of inhibitor mixtures. Clin Sci 61:487

    PubMed  Google Scholar 

  29. Will EJ, Bijvoet OLM, Van Der Linden HB (1976) Inhibition of calcium oxalate crystal growth: a simple method of measurement and preliminary results. In: Flesch H, Robertson WG, Smith LH (eds) Plenum Press, New York, p 367

    Google Scholar 

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Hennequin, C., Lalanne, V., Daudon, M. et al. A new approach to studying inhibitors of calcium oxalate crystal growth. Urol. Res. 21, 101–108 (1993). https://doi.org/10.1007/BF01788827

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