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Kinetics of calcium oxalate crystal formation in urine

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Abstract

It is routinely observed that persons with increased urinary stone risk factors do not necessarily form uroliths. Furthermore, stone formers can present with urinalyses that do not reflect the clinical picture. We explain this discrepancy by differences in crystallization kinetics. In 1162 urines, crystallization of Ca-oxalate was induced according to the BONN-Risk-Index (BRI) method. The urine’s relative light transmissivity (RLT) was recorded from 100 % at start of titration to 95 % due to nuclei formation and crystal growth. From the RLT changes, a measure of the thermodynamic inhibition threshold of crystal formation (BRI) and of crystal growth kinetics is derived (“turbidity slope” after crystallization onset). On average, subjects presenting with a low inhibition threshold, i.e., high BRI, also present significantly higher crystal growth rates compared with subjects in lower BRI classes. Only subjects in the highest BRI class show a lower growth rate than expected, probably due to a depletion of supersaturation by massive initial nucleation. With increasing thermodynamic risk of crystal formation (i.e., increasing BRI) due to an imbalance between inhibitors and promoters of crystal formation, an increase in the imbalance between inhibitors and promoters of crystal growth (i.e., increasing growth rate) is observed. Both lead to an increased urolith formation risk. Healthy subjects with increased BRI are an exception to this trend: their urine is thermodynamically prone to form stones, but they show a kinetic inhibition preventing nuclei from significant growth.

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Abbreviations

BRI:

BONN Risk Index

CaOx:

Calcium oxalate

COM:

Calcium oxalate monohydrate

COD:

Calcium oxalate dehydrate

NH4Ox:

Ammonium oxalate

References

  1. Trinchieri A (2008) Epidemiology of urolithiasis: an update. Clin Cases Miner Bone Metab 5:101–106

    PubMed  PubMed Central  Google Scholar 

  2. Stamatelou KK, Francis ME, Jones CA, Nyberg LM, Curhan GC (2003) Time trends in reported prevalence of kidney stones in the United States: 1976–1994. Kidney Int 63:1817–1823

    Article  PubMed  Google Scholar 

  3. Romero V, Haluk A, Assimos D (2010) Kidney stones: a global picture of prevalence, incidence and associated risk factors. Rev Urol 12:86–96

    Google Scholar 

  4. Manthey DE, Teichman J (2001) Nephrolithiasis. Emerg Med Clin N Am 19:633–654

    Article  CAS  Google Scholar 

  5. Nancollas GH (1982) Biological mineralization and demineralization. Springer, Berlin

    Book  Google Scholar 

  6. Evan AP, Lingeman JE, Coe FL, Parks JH, Bledsoe SB, Shao Y et al (2003) Randall’s plaque of patients with nephrolithiasis begins in basement membranes of thin loops of henle. J Clin Invest 111:607–616

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Lonsdale K (1968) Epitaxy as a growth factor in urinary calculi. Nature 217:56–58

    Article  CAS  PubMed  Google Scholar 

  8. Liebman M, Costa G (2000) Effects of calcium and magnesium on urinary oxalate excretion after oxalate loads. J Urol 163:1565–1569

    Article  CAS  PubMed  Google Scholar 

  9. Nicar MJ, Skurla C, Sakhaee K, Pak CYC (1983) Low urinary citrate excretion in nephrolithiasis. Urology 21:8–14

    Article  CAS  PubMed  Google Scholar 

  10. Kok DJ, Papapoulos SE, Bijvoet OL (1986) Excessive crystal agglomeration with low citrate excretion in recurrent stone-formers. Lancet 1:1056–1058

    Article  CAS  PubMed  Google Scholar 

  11. Schwille PO, Rumenapf G, Wolfel G, Kohler R (1988) Urinary pyrophosphate in patients with recurrent calcium urolithiasis and in healthy controls: a re-evaluation. J Urol 140:239–245

    CAS  PubMed  Google Scholar 

  12. Ryall RL (1996) Glycosaminoglycans, proteins, and stone formation: adult themes and child’s play. Pediatr Nephrol 10:656–666

    Article  CAS  PubMed  Google Scholar 

  13. Worcester EM, Beshensky AM (1995) Osteopontin inhibits nucleation of calcium oxalate crystals. Ann N Y Acad Sci 760:375–377

    Article  CAS  PubMed  Google Scholar 

  14. Wesson JA, Johnson RJ, Mazzali M, Beshensky AM, Stietz S, Giachelli C et al (2003) Osteopontin is a critical inhibitor of calcium oxalate crystal formation and retention in renal tubules. J Am Soc Nephrol 14:139–147

    Article  CAS  PubMed  Google Scholar 

  15. Webber D, Rodgers AL, Sturrock ED (2002) Synergism between urinary prothrombin fragment 1 and urine: a comparison of inhibitory activities in stone-prone and stone-free population groups. Clin Chem Lab Med 40:930–936

    Article  CAS  PubMed  Google Scholar 

  16. Grover PK, Ryall RL (1999) Inhibition of calcium oxalate crystal growth and aggregation by prothrombin and its fragments in vitro: relationship between protein structure and inhibitory activity. Eur J Biochem 263:50–56

    Article  CAS  PubMed  Google Scholar 

  17. Kobayashi H, Shibata K, Fujie M, Sugino D, Terao T (1998) Identification of structural domains in inter-alpha-trypsin involved in calcium oxalate crystallization. Kidney Int 53:1727–1735

    Article  CAS  PubMed  Google Scholar 

  18. Atmani F, Khan SR (1999) Role of urinary bikunin in the inhibition of calcium oxalate crystallization. J Am Soc Nephrol 10(Suppl 14):S385–S388

    CAS  PubMed  Google Scholar 

  19. Pillay SN, Asplin JR, Coe FL (1998) Evidence that calgranulin is produced by kidney cells and is an inhibitor of calcium oxalate crystallization. Am J Physiol 275:F255–F261

    CAS  PubMed  Google Scholar 

  20. Hess B, Zipperle L, Jaeger P (1993) Citrate and calcium effects on Tamm-Horsfall glycoprotein as a modifier of calcium oxalate crystal aggregation. Am J Physiol 265:F784–F791

    CAS  PubMed  Google Scholar 

  21. Knörle R, Schnierle P, Koch A, Buchholz NP, Hering F, Seiler H et al (1994) Tamm-horsfall glycoprotein: role in inhibition and promotion of renal calcium oxalate stone formation studied with fourier-transform infrared spectroscopy. Clin Chem 40:1739–1743

    PubMed  Google Scholar 

  22. Smith R, Levine J, Rosenfeld AT (1999) Helical CT of urinary tract stones: epidemiology, origin, pathophysiology, diagnosis, and management. Radiol Clin N Am 37:911–952

    Article  CAS  PubMed  Google Scholar 

  23. Knoll T, Schubert AB, Fahlenkamp D, Leusmann DB, Wendt-Nordahl G, Schubert G (2011) Urolithiasis through the ages: data on more than 200,000 urinary stone analyses. J Urol 185:1304–1311

    Article  PubMed  Google Scholar 

  24. Moses R, Pais VM Jr, Ursiny M, Prien EL Jr, Miller N, Eisner BH (2015) Changes in stone composition over two decades: evaluation of over 10,000 stone analyses. Urolithiasis 43:135–139

    Article  PubMed  Google Scholar 

  25. Lieske JC, Rule AD, Krambeck AE, Williams JC, Bergstralh EJ, Mehta RA et al (2014) Stone composition as a function of age and sex. Clin J Am Soc Nephrol 9:2141–2146

    Article  PubMed  PubMed Central  Google Scholar 

  26. Akin B, Oner M, Bayram Y, Demadis KD (2008) Effects of carboxylate-modified, green inulin biopolymers on the crystal growth of calcium oxalate. Cryst Growth Des 8:1997–2005

    Article  CAS  Google Scholar 

  27. Kirboga S, Oner M (2009) Inhibition of calcium oxalate crystallization by graft copolymers. Cryst Growth Des 9:2159–2167

    Article  CAS  Google Scholar 

  28. Milan A (2001) Crystal growth shape of whewellite polymorphs: influence of structure distortions on crystal shape. Cryst Growth Des 1:245–254

    Article  Google Scholar 

  29. Zhang DB, Qi LM, Ma JM, Cheng HM (2002) Morphological control of calcium oxalate dihydrate by a double-hydrophilic block copolymer. Chem Mater 14:2450–2457

    Article  CAS  Google Scholar 

  30. Echigo T, Kimata M, Kyono A, Shimizu M, Hatta T (2005) Re-investigation of the crystal structure of whewellite [Ca(C2O4)·H2O] and the dehydration mechanism of caoxite [Ca(C2O4)·3H2O]. Miner Mag 69:77–88

    Article  CAS  Google Scholar 

  31. Hamm LL, Hering-Smith KS (2002) Pathophysiology of hypocitraturic nephrolithiasis. Endocrinol Metab Clin N Am 31:885–893

    Article  CAS  Google Scholar 

  32. Spivacow FR, Del Valle EE, Negri AL, Fradinger E, Abib A, Rey P (2015) Biochemical diagnosis in 3040 kidney stone formers in Argentina. Urolithiasis 43:323–330

    Article  CAS  PubMed  Google Scholar 

  33. Amaro CR, Goldberg J, Damasio PC, Leitão VA, Turney B, Padovani CR, Amaro JL (2015) An update on metabolic assessment in patients with urinary lithiasis. World J Urol 33:125–129

    Article  CAS  PubMed  Google Scholar 

  34. Laube N, Kleinen L (2011) Risk indices. In: Rao NP, Preminger GM, Kavanagh JP (eds) Urinary tract stone disease. Springer, London, pp 355–368

    Google Scholar 

  35. Laube N, Hergarten S, Hoppe B, Schmidt M, Hesse A (2004) Determination of the calcium oxalate crystallization risk from urine samples: the BONN risk index in comparison to other risk formulas. J Urol 172:355–359

    Article  CAS  PubMed  Google Scholar 

  36. Kavanagh JP, Laube N (2006) Why does the bonn risk index discriminate between calcium oxalate stone formers and healthy controls? J Urol 175:766–770

    Article  PubMed  Google Scholar 

  37. Laube N, Berg W, Bernsmann F, Gravius S, Klein F, Latz S et al (2014) Induced urinary crystal formation as an analytical strategy for the prediction and monitoring of urolithiasis and other metabolism-related disorders. EPMA J 5:13

    Article  PubMed  PubMed Central  Google Scholar 

  38. Laube N, Hergarten S (2005) Can the bonn risk index be replaced by a simple measurement of the urinary concentration of free calcium ions? J Urol 173:2175–2177

    Article  CAS  PubMed  Google Scholar 

  39. Porowski T, Zoch-Zwierz W, Wasilewska A, Spotyk A, Konstantynowicz J (2007) Normative data on the bonn risk index for calcium oxalate crystallization in healthy children. Pediatr Nephrol 22:514–520

    Article  PubMed  PubMed Central  Google Scholar 

  40. Porowski T, Zoch-Zwierz W, Konstantynowicz J, Taranta-Janusz K (2008) A new approach to the diagnosis of children’s urolithiasis based on the bonn risk index. Pediatr Nephrol 23:1123–1128

    Article  PubMed  Google Scholar 

  41. Laube N, Pullmann M, Hergarten S, Hesse A (2003) Influence of urinary stones on the composition of a 24-hour urine sample. Clin Chem 49:281–285

    Article  CAS  PubMed  Google Scholar 

  42. Berg W, Bechler R, Laube N (2009) Analytical precision of the urolizer® for the determination of the BONN-risk-index (BRI) for calcium oxalate urolithiasis and evaluation of the influence of 24 h-urine storage at moderate temperatures on BRI. Clin Chem Lab Med 47:478–482

    Article  CAS  PubMed  Google Scholar 

  43. Berg W, Bechler R, Haas C, Laube N (2009) Relevance of the BONN risk index for metabolic monitoring of patients with calcium oxalate urolithiasis: a clinical application study of the urolizer. Urol Res 37:55–62

    Article  CAS  PubMed  Google Scholar 

  44. Coe FL, Parks JH, Nagakawa Y (1991) Protein inhibitors of crystallization. Semin Nephrol 11:98–109

    CAS  PubMed  Google Scholar 

  45. Rodgers AL, Webber D, Hibberd B (2015) Experimental determination of multiple thermodynamic and kinetic risk factors for nephrolithiasis in the urine of healthy controls and calcium oxalate stone formers: does a universal discriminator exist? Urolithiasis 43:479–487

    Article  CAS  PubMed  Google Scholar 

  46. Türk C, Knoll T, Petrik A, Sarica K, Skolarikos A, Straub M, Seitz C (2015) Guidelines on urolithiasis. Eur Assoc Urol. http://uroweb.org/wp-content/uploads/22-Urolithiasis_LR_full.pdf. Accessed 10 May 2016

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Correspondence to Norbert Laube.

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The authors declare that they have no conflict of interest. None of the employers played any role in the study design, in the collection, analysis, and interpretation of data, in the writing of the report or in the decision to submit the report for publication.

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Laube, N., Klein, F. & Bernsmann, F. Kinetics of calcium oxalate crystal formation in urine. Urolithiasis 45, 151–157 (2017). https://doi.org/10.1007/s00240-016-0900-y

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