Skip to main content
Log in

What does the crystallography of stones tell us about their formation?

  • Invited Review
  • Published:
Urolithiasis Aims and scope Submit manuscript

Abstract

The mineral phase makes up most of the mass of a kidney stone. Minerals all come in the form of crystals that are regular arrangements of atoms or molecular groupings at the atomic scale, bounded macroscopically by well-defined crystal faces. Pathologic nephroliths are a polycrystalline aggregate of submicron crystals. Organic macromolecules clearly have an important role in either promoting or preventing aggregation and in altering the morphology of individual submicron crystals by influencing the surface energies of different faces. Crystals, similar in morphology to those grown in solution, are often found for calcium oxalate dihydrate, brushite, cystine and struvite. This is not the case for calcium oxalate monohydrate and hydroxyapatite, two of the most common constituents of stones.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Al-Atar U, Bokov AA, Marshall D, Teichman JMH, Gates BD, Ye ZG, Branda NR (2010) Mechanism of calcium oxalate monohydrate kidney stones formation: layered spherulitic growth. Chem Mater 22:1318–1329

    Article  CAS  Google Scholar 

  2. Belcher AM, Wu XH, Christensen RJ, Hansma PK, Stucky GD, Morse DE (1996) Control of crystal phase switching and orientation by soluble mollusc shell proteins. Nature 381:56–58

    Article  CAS  Google Scholar 

  3. Beniash E, Aizenberg J, Addadi L, Weiner S (1997) Amorphous calcium carbonate transforms into calcite during sea urchin larval spicule growth. Proc R Soc Lond B 264:461–465

    Article  CAS  Google Scholar 

  4. Bigelow MW, Wiessner JH, Kleinman JG, Mandel NS (1996) Calcium oxalate-crystal membrane interactions: dependence on membrane lipid composition. J Urol 155:1094–1098

    Article  CAS  PubMed  Google Scholar 

  5. Boyce WH, Garvey FK (1956) The amount and nature of the organic matrix in urinary calculi: a review. J Urol 76:213–227

    CAS  PubMed  Google Scholar 

  6. Canales BK, Anderson L, Higgins L, Ensrud-Bowlin K, Roberts KP, Wu BL, Kim IW, Monga M (2010) Proteome of human calcium kidney stones. Urology 76(e1017):e13

    Google Scholar 

  7. Chauvet MC, Ryall RL (2005) Intracrystalline proteins and calcium oxalate crystal degradation in MDCK II cells. J Struct Biol 151:12–17

    Article  CAS  PubMed  Google Scholar 

  8. Daudon M, Bazin D, Andre G, Jungers P, Cousson A, Chevallier P, Veron E, Matzen G (2009) Examination of whewellite kidney stones by scanning electron microscopy and powder neutron diffraction techniques. J Appl Crystallogr 42:109–115

    Article  CAS  Google Scholar 

  9. Daudon M, Hennequin C, Boujelben G, Lacour B, Jungers P (2005) Serial crystalluria determination and the risk of recurrence in calcium stone formers. Kidney Int 67:1934–1943

    Article  PubMed  Google Scholar 

  10. De Yoreo JJ, Gilbert PUPA, Sommerdijk NAJM, Penn RL, Whitelam S, Joester D, Zhang H, Rimer JD, Navrotsky A, Banfield JF, Wallace AF, Michel FM, Meldrum FC, Colfen H, Dove PM (2015) Crystallization by particle attachment in synthetic, biogenic and geologic environments. Science 349:6760

    Article  Google Scholar 

  11. Deganello S (1981) The structure of whewellite, CaC2O4.H20 at 328K. Acta Crystallogr A B37:826–829

    Article  CAS  Google Scholar 

  12. Dorian HH, Rez P, Drach GW (1996) Evidence for aggregation in oxalate stone formation: atomic force and low voltage scanning electron microscopy. J Urol 156:1833–1837

    Article  CAS  PubMed  Google Scholar 

  13. Elliot JS, Rabinowitz IN (1980) Calcium oxalate crystalluria: crystal size in urine. J Urol 123:324–327

    CAS  PubMed  Google Scholar 

  14. Evan A, Lingeman J, Coe FL, Worcester E (2006) Randall’s plaque: pathogenesis and role in calcium oxalate nephrolithiasis. Kidney Int 69:1313–1318

    Article  CAS  PubMed  Google Scholar 

  15. Evan AP, Bledsoe SB, Smith SB, Bushinsky DA (2004) Calcium oxalate crystal localization and osteopontin immunostaining in genetic hypercalciuric stone-forming rats. Kidney Int 65:154–161

    Article  CAS  PubMed  Google Scholar 

  16. Evan AP, Coe FL, Lingeman JE, Shao Y, Sommer AJ, Bledsoe SB, Anderson JC, Worcester EM (2007) Mechanism of formation of human calcium oxalate renal stones on Randall’s plaque. Anat Record Adv Integr Anat Evol Biol 290:1315–1323

    Article  CAS  Google Scholar 

  17. Evan AP, Worcester EM, Coe FL, Williams J, Lingeman JE (2015) Mechanisms of human kidney stone formation Urolithiasis 43:S19–S32

    Google Scholar 

  18. Finlayson B, Reid F (1978) The expectation of free and fixed particles in stone disease. Investig Urol 15:442–448

    CAS  Google Scholar 

  19. Fleming DE, Riessen AV, Chauvet MC, Grover PK, Hunter B, Van Bronswijk W, Ryall RL (2003) Intracrystalline proteins and urolithiasis: a synchrotron X-ray diffraction study of calcium oxalate monohydrate. J Bone Min Res 18:1282–1291

    Article  CAS  Google Scholar 

  20. Frincu MC, Fogarty CE, Swift JA (2004) Epitaxial relationships between uric acid crystals and mineral surfaces: a factor in urinary stone formation. Langmuir 20:6524–6529

    Article  CAS  PubMed  Google Scholar 

  21. Ghosh S, Bhattacharya A, Chatterjee P, Mukherjee AK (2014) Structural and microstructural characterization of seven human kidney stones using FTIR spectroscopy, SEM, thermal study and X-ray Rietveld analysis. Z Kristallogr 229:451–458

    CAS  Google Scholar 

  22. Grohe B, O’Young J, Ionescu DA, Lajoie G, Rogers KA, Karttunen M, Goldberg HA, Hunter GK (2007) Control of calcium oxalate crystal growth by face specific adsorption of an osteopontin phosphopeptide. J Am Chem Soc 129:14946–14951

    Article  CAS  PubMed  Google Scholar 

  23. Gul A, Rez P (2007) Models for protein binding to calcium oxalate surfaces. Urol Res 35:63–71

    Article  CAS  PubMed  Google Scholar 

  24. Guo S, Ward MD, Wesson JA (2002) Direct visualisation of calcium oxalate monohydrate and crystallization and dissolution with atomic force microscopy and the role of polymeric additives. Langmuir 18:4284–4291

    Article  CAS  Google Scholar 

  25. Hahn T (ed) (2005) International tables for crystallography. International Union For Crystallography, Dordrecht

    Google Scholar 

  26. Hajir M, Graf R, Tremel W (2014) Stable amorphous calcium oxalate: synthesis and potential intermediate in biomineralization. Chem Commun 50:6534–6536

    Article  CAS  Google Scholar 

  27. He JY, Deng SP, Ouyang JM (2010) Morphology, particle size distribution, aggregation, and crystal phase of nanocrystallites in the urine of healthy persons and lithogenic patients. IEEE Trans Nanobiosci 9:156–163

    Article  Google Scholar 

  28. Herring LC (1962) Observations on the analysis of ten thousand urinary calculi. J Urol 88:545–562

    CAS  PubMed  Google Scholar 

  29. Ihli J, Wang YW, Cantaert B, Kim YY, Green DC, Bomans PHH, Sommerdijk N, Meldrum FC (2015) Precipitation of amorphous calcium oxalate in aqueous solution. Chem Mater 27:3999–4007

    Article  CAS  Google Scholar 

  30. Ihli J, Wong WC, Noel EH, Kim YY, Kulak AN, Christenson HK, Duer MJ, Meldrum FC (2014) Dehydration and crystallization of amorphous calcium carbonate in solution and air. Nat Commun 5:3169

    Article  PubMed  PubMed Central  Google Scholar 

  31. Iwata H, Iio S, Nishio S, Takeuchi M (1992) Architecture of mixed calcium oxalate dihydrate and monohydrate stones. Scanning Microsc 6:231–238

    CAS  PubMed  Google Scholar 

  32. Khan SR (1997) Calcium phosphate/calcium oxalate crystal association in urinary stones: implications for heterogeneous nucleation of calcium oxalate. J Urol 157:376–383

    Article  CAS  PubMed  Google Scholar 

  33. Khan SR, Glenton PA, Backov R, Talham DR (2002) Presence of lipids in urine, crystals and stones: implications for the formation of kidney stones. Kidney Int 62:2062–2072

    Article  CAS  PubMed  Google Scholar 

  34. Khan SR, Hackett RL (1986) Identification of urinary stone and sediment crystals by scanning electron microscopy and X-ray microanalysis. J Urol 135:818–826

    CAS  PubMed  Google Scholar 

  35. King JS, Boyce WH (1957) Amino acid and carbohydrate composition of the mucoprotein matrix in various calculi. Proc Soc Exp Biol Med 95:183–187

    Article  CAS  PubMed  Google Scholar 

  36. Kok DJ, Khan SR (1994) Calcium oxalate nephrolithiasis, a free or fixed particle disease. Kidney Int 46:847–854

    Article  CAS  PubMed  Google Scholar 

  37. Letellier JR, Lochlear MJ, Campbell AA, Vogel V (1998) Oriented growth of calcium oxalate monohydrate crystals between phospholipid monolayers. Biochim Biophys Acta 1380:31–45

    Article  CAS  PubMed  Google Scholar 

  38. Li H, Xin HL, Muller DA, Estroff LA (2009) Visualizing the 3D internal structure of calcite single crystals grown in agarose hydrogel. Science 326:1244–1247

    Article  CAS  PubMed  Google Scholar 

  39. Lian JB, Prien EL, Glimcher MJ, Gallop PM (1977) The presence of protein bound γ-carboxyglutamic acid in calcium-containing renal calculi. J Clin Invest 59:1151–1157

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  41. Mahamid J, Sharir A, Addadi L, Weiner S (2008) Amorphous calcium phosphate is a major component of the forming fin bones of zebrafish: indications for an amorphous precursor phase. Proc Natl Acad Sci 105:12748–12753

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Mandal T, Ward MD (2013) Determination of specific binding interactions at l-cystine crystal surfaces with chemical force microscopy. J Am Chem Soc 135:5525–5528

    Article  CAS  PubMed  Google Scholar 

  43. Mandel N (1994) Crystal-membrane interaction in kidney stone disease. J Am Soc Nephrol 5:S37–S45

    CAS  PubMed  Google Scholar 

  44. Mandel N, Riese R (1991) Crystal cell interactions: crystal binding to rat renal papillary tip collecting duct cells in culture. Am J Kidney Dis 17:402–406

    Article  CAS  PubMed  Google Scholar 

  45. Meyer AS, Finlayson B, DuBois L (1971) Direct observation of urinary stone ultrastructure. Brit J Urol 43:154–163

    Article  CAS  PubMed  Google Scholar 

  46. Millan A (2001) Crystal growth of whewellite polymorphs: influence of structure distortions on crystal shape. Cryst Growth Design 1:245–254

    Article  CAS  Google Scholar 

  47. Ogbuji LU, Finlayson B (1981) Crystal morphologies in whewellite stones: electron microscopy. Investig Urol 19:182–186

    Google Scholar 

  48. Politi Y, Metzler R, Abrecht M, Gilbert B, Wilt FH, Sagi I, Addadi L, Weiner S, Gilbert PUPA (2008) Transformation mechanism of amorphous calcium carbonate into calcite in the sea urchin larval spicule. PNAS 105:17362–17366

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Prien EL, Prien EL (1968) Composition and structure of urinary stone. Am J Med 45:654–672

    Article  CAS  PubMed  Google Scholar 

  50. Qiu SR, Wierzbicki A, Orme CA, Cody AM, Hoyer JR, Nancollas GH, Zepeda S, De Yoreo JJ (2004) Molecular modulation of calcium oxalate crystallization by osteopontin and citrate. Proc Natl Acad Sci 101:1811–1815

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Qiu SR, Wierzbicki A, Salter EA, Zepeda S, Orme CA, Hoyer JR, Nancollas GH, Cody AM, de Yoreo JJ (2005) Modulation of calcium oxalate monohydrate crystallization by citrate through selective binding to atomic steps. J Am Chem Soc 127:9036–9044

    Article  CAS  PubMed  Google Scholar 

  52. Rez P, Sinha S, Gal A (2014) Nanocrystallite model for amorphous calcium carbonate. J Appl Cryst 47:1651–1657

    Article  CAS  Google Scholar 

  53. Riese RJ, Riese JW, Kleinman JG, Wiessner JH, Mandel GS, Mandel NS (1988) Specificity in calcium oxalate adherence to papillary epithelial cells. Am J Physiol 255:F1025–F1032

    CAS  PubMed  Google Scholar 

  54. Robertson WG, Peacock M, Nordin BEC (1971) Calcium oxalate crystalluria and urine saturation in recurrent renal stone-formers. Clin Sci 40:365–374

    Article  CAS  PubMed  Google Scholar 

  55. Rodgers AL (1983) Common ultrastructural features in human calculi. Micron 14:219–224

    Google Scholar 

  56. Rodgers AL, Cox TA, Noakes TD, Lombard CJ (1992) Crystalluria in marathon runners IV black subjects. Urol Res 20:27–33

    Article  CAS  PubMed  Google Scholar 

  57. Rodgers AL, Greyling KG, Irving RA, Noakes TD (1988) Crystalluria in marathon runners II ultra-marathon—males and females. Urol Res 16:89–93

    Article  CAS  PubMed  Google Scholar 

  58. Rodgers AL, Greyling KG, Noakes TD (1991) Crystalluria in marathon runners III stone-forming subjects. Urol Res 19:189–192

    Article  CAS  PubMed  Google Scholar 

  59. Ryall RL, Chauvet MC, Grover PK (2005) Intracrystalline proteins and urolithiasis: a comparison of the protein content and ultrastructure of urinary calcium oxalate monohydrate and dihydrate crystals. BJU Int 96:654–663

    Article  CAS  PubMed  Google Scholar 

  60. Ryall RL, Fleming DE, Doyle IR, Evans NA, Dean CJ, Marshall VR (2001) Intracrystalline proteins and the hidden ultrastructure of calcium oxalate urinary crystals: implications for kidney stone formation. J Struct Biol 134:5–14

    Article  Google Scholar 

  61. Ryall RL, Fleming DE, Grover PK, Chauvet M, Dean CJ, Marshall VR (2000) The hole truth: Intracrystalline proteins and calcium oxalate kidney stones. Mol Urol 4:391–402

    CAS  PubMed  Google Scholar 

  62. Ryall RL, Grover PK, Turgood LA, Chauvet MC, Fleming DE, van Bronswijk W (2007) The importance of a clean face: the effect of different washing procedures on the association of Tamm–Horsfall glycoprotein and other urinary proteins with calcium oxalate crystals. Urol Res 35:1–14

    Article  CAS  PubMed  Google Scholar 

  63. Sandersius S, Rez P (2007) Morphology of crystals in calcium oxalate kidney stones. Urol Res 35:287–293

    Article  CAS  PubMed  Google Scholar 

  64. Schubert G, Brien G (1981) Crystallographic investigations of urinary calcium oxalate calculi. Int Urol Nephrol 13:249–260

    Article  CAS  PubMed  Google Scholar 

  65. Schubert G, Brien G, Lenk S, Koch R (1983) Texture examinations on grain and thin section preparations of calcium oxalate calculi and their relations to pathogenetic parameters. Urol Res 11:111–115

    Article  CAS  PubMed  Google Scholar 

  66. Sheng X, Ward MD, Wesson JA (2003) Adhesion between molecules and calcium oxalate crystals: Critical interactions in kidney stone formation. J Am Chem Soc 125:2854–2855

    Article  CAS  PubMed  Google Scholar 

  67. Sheng XX, Jung TS, Wesson JA, Ward MD (2005) Adhesion at calcium oxalate crystal surfaces and the effect of urinary constituents. Proc Natl Acad Sci 102:267–272

    Article  CAS  PubMed  Google Scholar 

  68. Sours RE, Fink DA, Cox KA, Swift JA (2005) Uric acid dye inclusion crystals. Mol Cryst Liq Cryst 440:187

    Article  CAS  Google Scholar 

  69. Spector M, Garden NM, Rous SN (1978) Utrastructure and pathogenesis of human urinary calculi. Br J Urol 50:12–15

    Article  CAS  PubMed  Google Scholar 

  70. Stapleton AMF, Ryall RL (1995) Blood coagulation proteins and urolithiasis are linked: crystal matrix protein is the F1 activation peptide of human prothrombin. Br J Urol 75:712–719

    Article  CAS  PubMed  Google Scholar 

  71. Stapleton AMF, Simpson RJ, Ryall RL (1993) Crystal matrix protein is related to human prothrombin. Biochem Biophys Res Commun 195:1199–1203

    Article  CAS  PubMed  Google Scholar 

  72. Talham DR, Backov R, Benitez IO, Sharbaugh DM, Whipps S, Khan SR (2006) Role of lipids in urinary stones: studies of calcium oxalate precipitation at phospholipid langmuir monolayers. Langmuir 22:2450–2456

    Article  CAS  PubMed  Google Scholar 

  73. Tazzoli V, Domeneghetti C (1980) The crystal structures of whewellite and weddellite: re-examination and comparison. Am Mineral 65:327–334

    CAS  Google Scholar 

  74. Thomas A, Rosseeva E, Hochrein O, Carrillo-Cabrera W, Simon P, Duchstein P, Zahn D, Kniep R (2012) Mimicking the growth of a pathologic biomineral: shape development and structures of calcium oxalate dihydrate in the presence of polyacrylic acid. Chem–A Eur J 18:4000–4009

    Article  CAS  Google Scholar 

  75. Werness PG, Bergert JH, Smith LH (1981) Crystalluria. J Cryst Growth 53:166–181

    Article  Google Scholar 

  76. Werness PG, Duckworth SC, Smith LH (1979) Calcium oxalate dihydrate crystal growth. Investig Urol 17:230–233

    CAS  Google Scholar 

  77. Wesson JA, Ward MD (2007) Pathological biomineralization of kidney stones. Elements 3:415–421

    Article  CAS  Google Scholar 

  78. Whipps S, Khan SR, Palko FJ, Backov R, Talham DR (1998) Growth of calcium oxalate monohydrate at phospholipid Langmuir monolayers. J Cryst Growth 192:243–249

    Article  CAS  Google Scholar 

  79. Wulff G (1901) On the question of speed of growth and dissolution of crystal surfaces. Z Kristallogr und Mineral 34:449–530

    CAS  Google Scholar 

Download references

Acknowledgements

I would like to acknowledge financial support from the Rosi and Max Varon visiting professorship while at the Weizmann Institute of Science. Profs Steve Weiner and Lia Addadi made many useful suggestions, and Dr. Eugenia Klein helped in acquisition of SEM micrographs. I’d also like to acknowledge discussions with Prof. Saeed Khan and Dr. Jeff Wesson.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Peter Rez.

Ethics declarations

Conflict of interest

The author has no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rez, P. What does the crystallography of stones tell us about their formation?. Urolithiasis 45, 11–18 (2017). https://doi.org/10.1007/s00240-016-0951-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00240-016-0951-0

Keywords

Navigation