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A hypothesis of calcium stone formation: an interpretation of stone research during the past decades

Urological Research volume 39, pages 231–243 (2011)Cite this article

Abstract

An interpretation of previous and recent observation on calcium salt crystallization and calcium stone formation provide the basis for formulation of a hypothetical series of events leading to calcium oxalate (CaOx) stone formation in the urinary tract. The various steps comprise a primary precipitation of calcium phosphate (CaP) at high nephron levels, establishment of large intratubular and/or interstitial (sub-epithelial) aggregates of CaP. These crystal masses subsequently might be dissolved during periods with low urine pH. On the denuded surface of subepithelial or intratubularly trapped CaP, release of calcium ions can result in very high ion-activity products of CaOx, particularly during simultaneous periods with peaks of CaOx supersaturation. Crystals of CaOx may result from nucleation in the macromolecular environment surrounding the apatite crystal phase. In the presence of low pH, low citrate and high ion-strength of urine, formation of large CaOx crystal masses can be accomplished by self-aggregation of Tamm–Horsfall mucoprotein. Following dislodgment of the initially fixed CaOx stone embryo, the further development into to clinically relevant stone is accomplished by CaOx crystal growth and CaOx crystal aggregation of the retained stone material. The latter process is modified by a number of inhibitors and promoters present in urine. The retention of the stone is a consequence of anatomical as well as hydrodynamic factors.

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References

  1. Tiselius HG (1996) Solution chemistry of supersaturation. In: Coe FL, Favus MJ, Pak CYC, Parks JH, Preminger GM (eds) Kidney stones: medical and surgical management. Lippincott-Raven Publishers, Philadelphia, pp 33–64

    Google Scholar 

  2. Wendt-Nordahl G, Evan AP, Spahn M, Knoll T (2008) Calcium oxalate stone formation. New pathogenetic aspects of an old disease. Urologe A 47:540–544

    Google Scholar 

  3. Hess B, Kok DJ (1996) Nucleation, growth and aggregation of stone-forming crystals. In: Coe FL, Favus MJ, Pak CYC, Parks JH, Preminger GM (eds) Kidney stones: medical and surgical management. Lippincott-Raven Publishers, Philadelphia, pp 3–32

    Google Scholar 

  4. Achilles W (1997) In vitro crystallization systems for the study of urinary stone formation. World J Urol 244–251

  5. Robertson WG, Peacock M, Heyburn PJ, Marshall DH, Clark PB (1978) Risk factors n calcium stone disease of the urinary tract. Br J Urol 50:449–454

    PubMed  CAS  Article  Google Scholar 

  6. Nancollas GH (1983) Crystallization theory relating to urinary stone formation. World J Urol 1:131–137

    Article  Google Scholar 

  7. Khan S, Kok D (2004) Modulators of urinary stone formation. Front Biosci 9:1450–1482

    PubMed  CAS  Article  Google Scholar 

  8. Coe FL, Parks JH, Nakagawa Y (1991) Protein inhibitors of crystallization. Semin Urol 11:98–109

    CAS  Google Scholar 

  9. Scurr DS, Robertson WG (1986) Modifiers of calcium oxalate crystallization found in urine. III studies on the role of Tamm–Horsfall mucoprotein and ionic strength. J Urol 136:505–507

    PubMed  CAS  Google Scholar 

  10. Roberston WG, Scurr DS, Bridge M (1981) Factors influencing the crystallisation of calcium oxalate—critique. J Cryst Growth 53:182–194

    Article  Google Scholar 

  11. Lieske JC, Walsh-Reitz MM, Toback FG (1992) Calcium oxalate monohydrate crystals are endocytosed by renal epithelial cells and induce proliferation. Am J Physiol (Renal Electrolyte Physiol) 262:F622–F630

    CAS  Google Scholar 

  12. Yuen J, Gohel M, Poon N, Shum D, Tam PA, Au DW (2010) The initial and subsequent inflammatory events during calcium oxalate lithiasis. Clin Chim Acta 411:15–16

    Article  CAS  Google Scholar 

  13. Vervaet B, Vehulst A, De Broe M, D′Haese P (2010) The tubular epithelium in the initiation and course of intratubular nephrocalcinosis. Urol Res 38:249–256

    PubMed  Article  Google Scholar 

  14. Evan AP, Lingeman JE, Coe FL, Worcester EM (2008) Role of interstitial apatite plaque in the pathogenesis of the common calcium oxalate stone. Semin Nephrol 28:111–119

    PubMed  CAS  Article  Google Scholar 

  15. Matlaga BR, Kim JCW, Kuo RL, Evan AP, Bledsoe SB, Coe FL, Worcester EM, Munch LC, Lingeman JE (2006) Endoscopic evidence of calculus attachment to Randal’s plaque. J Urol 175:1720–1724

    PubMed  Article  Google Scholar 

  16. Randall A (1940) Papillary pathology as a precursor of primary renal calculus. J Urol 44:580

    CAS  Google Scholar 

  17. Smith LH, Werness PG (1983) Hydroxyapatite—the forgotten crystal in calcium urolithiasis. Trans Am Clin Chem Assoc 95:183–190

    Google Scholar 

  18. Öhman S, Larsson L, Tiselius HG (1992) Clinical significance of phosphate in calcium oxalate renal stones. Ann Clin Biochem 29:59–63

    PubMed  Google Scholar 

  19. Leusmann DB, Blanschke R, Schwandt W (1990) Results of 5035 stone analyses: a contribution to epidemiology of urinary stone disease. Scand J Urol Nephrol 24:205–210

    PubMed  CAS  Article  Google Scholar 

  20. Tiselius HG, Larsson L (1993) Calcium phosphate—an important crystal phase in patients with recurrent calcium stone formation? Urol Res 21:175–180

    PubMed  CAS  Article  Google Scholar 

  21. Grases F, March JG, Conte A, Costa-Bautzá A (1993) New aspects on the composition, structure and origin of calcium oxalate monohydate calculi. Eur Urol 24:381–386

    PubMed  CAS  Google Scholar 

  22. Fernandez-Conde M, Alcover J, Barastegui C, Carretero P (1995) Calculi of papillary origin. Ann Urol (Paris) 29:351–354

    CAS  Google Scholar 

  23. Prien EL Sr (1975) The riddle of Randall′s plaques. J Urol 114:500–507

    PubMed  CAS  Google Scholar 

  24. Miller NL, Evan AP, Lingeman JE (2007) Pathogenesis of renal calculi. Urol Clin North Am 34:295–313

    PubMed  Article  Google Scholar 

  25. de Bruijn WC, Boevé ER, van Run PR, van Miert PP, de Water R, Romijn JC, Verkoelen CF, Cao LC, van’t Noordende JM, Schröder FH (1995) Etiology of calcium oxalate nephrolithiasis in rats. II. Scanning Microsc 9:124–125

    Google Scholar 

  26. Evan AP (2009) Physiopathology and etiology of stone formation in the kidney and the urinary tract. Pediatr Nephrol 25:831–841

    PubMed  Article  Google Scholar 

  27. Coe FL, Evan AP, Lingeman JE, Worcester EM (2010) Plaque and deposits in nine human stone diseases. Urol Res 38:239–247

    PubMed  Article  Google Scholar 

  28. Ahlstrand C, Tiselius HG, Larsson L (1984) Studies on crystalluria in calcium oxalate stone formers. Urol Res 12:103–106

    PubMed  CAS  Article  Google Scholar 

  29. Kok DJ (1996) Free and fixed particle mechanism, a review. Scanning Microsc 10:471–486

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Article  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  32. Kok DJ, Khan SR (1995) Chances for free or fixed particle mechanism. In: Rao PN, Kavanagh JP, Tiselius HG (eds) Urolithiasis Consensus and Controversies. Lithtripter Unit, Withington Hospital, Manchester, pp 431–432

    Google Scholar 

  33. Crassweller PO, Brandes L, Katrizoglou A, Oreopoulos DG (1979) Studies on crystalluria in recurrent calcium lithiasis. Can J Surg 22:527–529

    PubMed  CAS  Google Scholar 

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

    Article  Google Scholar 

  35. Adamthwaite DN (1983) Urinary particulate activity in urinary calculus disease. Br J Urol 55:95–99

    PubMed  CAS  Article  Google Scholar 

  36. Asplin J, DeGanello S, Nakgawa YN, Coe F (1991) Evidence for calcium phosphate supersaturation in the loop of Henle. Am J Physiol 270:F604–F613

    Google Scholar 

  37. Tiselius HG, Hojgaard I (1999) Some aspects of the intratubular precipitation of calcium salts. J Am Soc Nephrol 10:S373–S375

    Google Scholar 

  38. Asplin JR, Mandel NS, Coe FL (1996) Evidence of calcium phosphate supersaturation in the loop of Henle. Am J Physiol 270:F604–F613

    PubMed  CAS  Google Scholar 

  39. Luptak J, Bek-Jensen H, Fornander AM, Hojgaard I, Nilsson MA, Tiselius HG (1994) Crystallization of calcium oxalate and calcium phosphate at supersaturation levels corresponding to those in different parts of the nephron. Scanning Microsc 8:47–62

    CAS  Google Scholar 

  40. Hojgaard I, Fornander AM, Nilsson MA, Tiselius HG (1996) Crystallisation during volume reduction of solutions with an ion-composition corresponding to that in the distal tubuli. Scanning Microsc 10:487–498

    PubMed  CAS  Google Scholar 

  41. Berg C, Tiselius HG (1986) The effect of pH on the risk of calcium oxalate crystallization in urine. Eur Urol 12:59–61

    PubMed  CAS  Google Scholar 

  42. Christoffersen MR, Christoffersen J, Kibalczyc W (1990) Apparent solubilities of two amorphous calcium phosphates and of octa calcium phosphate in the temperature range 30–42°C. J Cryst Growth 106:349–354

    CAS  Article  Google Scholar 

  43. DeGanello S, Asplin J, Coe FL (1990) Evidence that the fluid in the thin segment of the loop of Henle normally is supersaturated and forms poorly crystallized hydroxyapatite that can initiate renal stones. (Abstract). Kidney Int 37:472

    Google Scholar 

  44. Koutsoukos PG, Nancollas GH (1981) Crystal growth of calcium phosphates—epitaxial considerations. J Cryst Growth 53:10–19

    CAS  Article  Google Scholar 

  45. Hojgaard I, Tiselius HG (1999) Crystallisation in the nephron. Urol Res 27:397–403

    PubMed  CAS  Article  Google Scholar 

  46. Lundager-Madsen HE, Christensson F (1991) Precipitation of calcium phosphate at 40°C from neutral solution. J Cryst Growth 114:613–618

    Article  Google Scholar 

  47. Baumann JM, Ackermann D, Affolter B (1989) The influence of hydroxyapatite and pyrophosphate on the formation product of calcium oxalate at different pHs. Urol Res 17:153–155

    PubMed  CAS  Google Scholar 

  48. Khori KMK, Ishikawa Y, Katayama Y, Takada M, Katoh Y, Kataoka K, Iguchi M, Kurita T (1991) Relationship between metabolic acidosis and calcium phosphate stone formation in women. Int Urol Nephrol 23:307–316

    Article  Google Scholar 

  49. Evan AP, Lingeman J, Coe FL, Parks JH, Bledsoe SB, Shao Y, Sommer AJ, Paterson RF, Kuo RL, Grynpas M (2003) Randall’s plaques of patients with nephrolithiasis begins in basement membranes of the loop of Henle. J Clin Invest 111:602–605

    Google Scholar 

  50. Sepe V, Adamo G, La Fianza A, Libetta C, Giuliano MG, Soccio G (2006) Henle loop basement membrane as initial site for Randall plaque formation. Am J Kidney Dis 48:706–711

    PubMed  CAS  Article  Google Scholar 

  51. Tiselius HG (1996) Estimated levels of superstauration with calcium phosphate and calcium oxalate in the distal tubuli. Urol Res 25:153–159

    Article  Google Scholar 

  52. Tiselius HG, Hallin A, Lindbäck B (2001) Crystallisation properties in stone forming and normal subjects urine diluted using a standardized procedure to match the composition of urine in the distal part of the distal tubule and the middle part of the collecting duct. Urol Res 29:75–82

    PubMed  CAS  Article  Google Scholar 

  53. Kok DJ, Schell-Feith EA (1999) Risk factors for crystallisation in the nephron: the role of renal develpment. J Am Soc Nephrol 10:S364–S370

    PubMed  Google Scholar 

  54. Hering F, Lueoend G, Briellmann T, Seiler H, Guggenheim H, Rutishauser G (1988) Stone formation in the human kidney. In: Walker VR, Sutton RL, Cameron B, Pak CYC, Roberston WG (eds) Urolithiasis. Plenum Press, New York, pp 73–74

    Google Scholar 

  55. Evan AP, Lingeman JE, Coe FL, Bledsoe SB, Sommer AJ, Williams JC Jr, Krambeck AE, Worcester EM (2009) Intratubular deposits, urine and stone composition are divergent in patients with ileostomy. Kidney Int 76:1081–1088

    PubMed  CAS  Article  Google Scholar 

  56. Resnick MI, Boyce WH (1978) Sperical calcium bodies in stone-forming urine. Invest Urol 15:449–451

    PubMed  CAS  Google Scholar 

  57. Achilles W, Jockel U, Schaper A, Ulshofer B, Riedmiller H (1994) Formation of urinary stones in vitro: growth of calcium oxalate on spherulites of calcium phosphate in gel. In: Ryall R, Bais R, Marshall VR, Rofe AM, Smith LH, Walker VR (eds) Urolithiasis, vol 2. Plenum Press, New York, pp 161–165

    Google Scholar 

  58. Fan J, Chandoke PS (1999) Examination of crystalluria in freshly voided urines of recurrent calcium stone formers and normal individuals using a new filter technique. J Urol 161:1685–1688

    PubMed  CAS  Article  Google Scholar 

  59. Borghi L, Meschi T, Guerra A, Bergamaschi E, Mutti A, Novarini A (1995) Effect of urinary acromolecules on the nucleation of calcium oxalate in idiopathic stone formers and healthy controls. Clin Chim Acta 239:1–11

    PubMed  CAS  Article  Google Scholar 

  60. Carvalho M, Mulinari R, Nakagawa Y (2002) Role of Tamm–Horsfall protein and uromodulin in calcium oxalate crystallization. Br J Med Biol Res 35:1165–1172

    CAS  Article  Google Scholar 

  61. Maslamani S, Glenton PA, Khan SR (2000) Changes in urine macromolecular composition during processing. J Urol 164:230–236

    PubMed  CAS  Article  Google Scholar 

  62. Gorski JP (1992) Acidic phosphoproteins from bone matrix: a structural rationalization of their role in biomineralization. Calif Tissue Int 50:391–396

    CAS  Article  Google Scholar 

  63. Fasano JM, Khan S (2001) Intratubular crystallisation of calcium oxalate in the presence of membrane vesicles: an in vitro study. Kidney Int 59:169–178

    PubMed  CAS  Article  Google Scholar 

  64. 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

    PubMed  CAS  Article  Google Scholar 

  65. Wuthier RE (1973) The role of phospholipids in biological calcification: Distribution of phospholipase activity in calcifying epiphyseal cartilage. Clin Orthoped Relat Res 90:191–200

    Google Scholar 

  66. Wang L, Guan X, Tang R, Hoyer J, Wierzbicki A, De Yorero J, Nancollas G (2008) Phosphorylation of osteopontin is required for inhibition of calcium oxalate crystallization. J Phys Chem B 112:9151–9157

    PubMed  CAS  Article  Google Scholar 

  67. Gebauer D, Völkel A, Cölfen H (2008) Stable prenucleation calcium carbonate clusters. Science 322:1819–1822

    PubMed  CAS  Article  Google Scholar 

  68. Bauman JM, Affolter B, Caprez U, Henze U, Lauper D, Maier F (2001) Hydroxyapatite induction and secondary aggregation, two important processes in calcium stone formation. Urol Res 29:417–422

    Article  CAS  Google Scholar 

  69. Nakagawa Y, Ahmed MA, Hall SL, Deganello S, Coe FL (1987) Isolation from human calcium oxalate renal stones of nephrocalcin, a glycoprotein inhibitor of calcium oxalate crystal gowth. J Clin Invest 79:1782–1787

    PubMed  CAS  Article  Google Scholar 

  70. Coe FL, Nakagawa Y, Parks JH (1991) Inhibitors within the nephron. Am J Kidney Dis 17:407–413

    PubMed  CAS  Google Scholar 

  71. Ryall RL, Harnett RM, Hibbers CM, Edyvane KA, Marshall VR (1991) Effects of chondroitin sulphate, human serum albumin and Tamm–Horsfall mucoprotein on calcium oxalate crystallizaion in undiluted human urine. Urol Res 19:181–188

    PubMed  CAS  Article  Google Scholar 

  72. Khan SR (1995) Experimental calcium oxalate nephrolithiasis and the formation human urinary stones. Scanning Microsc 9:89–100

    PubMed  CAS  Google Scholar 

  73. Khan SR, Hackett RL (1991) Retention of calcium oxalate crystals in renal tubules. Scanning Microsc 5:711–712

    Google Scholar 

  74. Evan AP, Lingeman JE, Coe FL, Parks JH, Bledsoe SB, Shao Y, Sommer AJ, Paterson RF, Kuo RL, Grynpas M (2003) Randall’s plaque of patients with nephrolithiasis begins in the basement membranes of the thin loops of Henle. J Clin Invest 111:607–616

    PubMed  CAS  Google Scholar 

  75. Coe FL, Evan AP, Worcester EM, Lingeman JE (2010) Three pathways for human kidney stones formation. Urol Res 38:147–160

    PubMed  Article  Google Scholar 

  76. Pak CYC (1981) Potential etiologic role of brushite in the formation of calcium (renal) stones. J Cryst Growth 53:202–208

    CAS  Article  Google Scholar 

  77. Matlaga BR, Coe FL, Evans APELJ (2007) The role of Randall’s plaque in the pathogenesis of calcium stones. J Urol 177:31–38

    PubMed  Article  Google Scholar 

  78. 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 Rec 290:1315–1323

    CAS  Article  Google Scholar 

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

    PubMed  CAS  Article  Google Scholar 

  80. Kleinman J, Alatalo L, Beshensky A, AE J (2008) Acidic polyanion poly(acrylic acid) prevents calcium oxalate deposition. Kidney Int 74:919–924

    PubMed  CAS  Article  Google Scholar 

  81. Fleisch H (1978) Inhibitors and prompters of stone formation. Kidney Int 13:361–371

    PubMed  CAS  Article  Google Scholar 

  82. Sutor DJ, Percival JM, Piper KAJ (1979) Urinary inhibitors of calcium phosphate formation: the inhibitory activity in artificial urines. Br J Urol 51:1–5

    PubMed  CAS  Article  Google Scholar 

  83. Györy AZ, Ashby R (1999) Calcium salt urolithiasis. Review of theory for diagnosis and management. Clin Nephrol 51:197–208

    PubMed  Google Scholar 

  84. Kok D, Papapoulos SE, Blomen LJMJ, Bijvoet OLM (1988) Modulation of calcium oxalate monohydrate crystallization kinetics in vitro. Kidney Int 34:346–350

    PubMed  CAS  Article  Google Scholar 

  85. Kok D, Papapoulos SE, Bijvoet OLM (1986) Excessive crystal agglomeration with low citrate excretion in recurrent stone-formers. Lancet 1056–1058

  86. Tiselius HG (1984) Urinary pH and calcium oxalate crystallization. In: Fortschritte der Urolige und Nephrologie. Pathogenese und Klinik der Harnsteinae X. (eds Vahlensieck W, Gasser, G). Steinkopff, Darmstadt 22:184–187

  87. Moreno EC, Varughese K (1981) Crystal growth of calcium apatites from dilute solutions. J Cryst Growth 53:20–30

    CAS  Article  Google Scholar 

  88. Meyer JL, Smith LH (1975) Growth of calcium oxalate crystals. II Inhibition by natural crystal growth inhibitors. Invest Urol 13:36–39

    PubMed  CAS  Google Scholar 

  89. Morse RM, Resnick MI (1988) A new approach to the study of urinary macromolecules as a participant in calcium oxalate crystallization. J Urol 139:869–873

    PubMed  CAS  Google Scholar 

  90. Curreri PA, Onoda G, Finlayson B (1981) A comparative appraisal of adsorption of citrate on whewellite seed crystals. J Cryst Growth 53:209–214

    CAS  Article  Google Scholar 

  91. Robertson WG, Peacock M, Marshall RW, Marshall DHCNBE (1976) Saturation-inhibition index as a measure of the risk of calcium oxalate stone formation in the urinary tract. New Engl J Med 294:249–252

    PubMed  CAS  Article  Google Scholar 

  92. Atmani F, Glenton PA, Khan SR (1998) Identification of proteins extracted from calcium oxalate and calcium phosphate crystals induced in the urine of healthy and stone forming subjects. Urol Res 26:201–207

    PubMed  CAS  Article  Google Scholar 

  93. Hojgaard I, Fornander AM, Nilsson MA, Tiselius HG (1998) The influence of hydroxyapatite seed on the crystallisation induced by volume reduction of solutions with an ion composition corresponding to that in the distal tubule at different pH levels. Scand J Urol Nephrol 32:311–319

    PubMed  CAS  Article  Google Scholar 

  94. Mandel N, Mandel G (1990) Epitaxis in renal stones. In: Wickham JA, Buck AC (eds) Renal tract stone. Churchill Livingstone, London, pp 87–101

    Google Scholar 

  95. Khan SR, Glenton PA (2010) Experimental induction of calcium oxalate nephrolithiasis in mice. J Urol 184:1189–1196

    PubMed  CAS  Article  Google Scholar 

  96. Embery G, Rees S, Hall R, Rose K, Waddington R, Shellis P (1998) Calcium- and apatite-binding properties of glucuronic acid-rich and iduronic acid-rich glycosmanoglycans and proteoglycans. Eur J Oral Sci 106(suppl 1):267–273

    PubMed  CAS  Google Scholar 

  97. Hess B (1994) Tamm–Horsfall glycoprotein and calcium nephrolithiasis. Miner Electrolyte Metab 20:393–398

    PubMed  CAS  Google Scholar 

  98. Gault MH, Chafe LL, Morgan JM, Parfrey PS, Harnett JD, Walsh EA, Prabhakaran VM, Dow D, Colpitts A (1991) Comparison of patients with idiopathic calcium phosphate and calcium oxalate stones. Medicine 70:345–359

    PubMed  CAS  Article  Google Scholar 

  99. Grover PK, Thurgood LA, Fleming DE, van Bronswijk W, Wang T, Ryall RL (2008) Intracrystalline urinary proteins facilitate degradation and dissolution of calcium oxalate crystals in cultured cells. Am J Physiol Renal Physiol 294:F355–F361

    PubMed  CAS  Article  Google Scholar 

  100. Tiselius HG, Lindbäck B, Fornander AM, Nilsson MA (2009) Studies on the role of calcium phosphate in the process of calcium oxalate crystal formation. Urol Res 37:181–192

    PubMed  CAS  Article  Google Scholar 

  101. Leal JJ, Finlayson B (1977) Adsorption of naturally occurring polymers onto calcium oxalate crystal surfaces. Invest Urol 14:278–283

    PubMed  CAS  Google Scholar 

  102. Robertson WG, Heyburn PJ, Peacock M, Hanes FA, Swaminathan R (1979) The effect of high animal protein intake on the risk of calcium stone-formation in the urinary tract. Clin Sci 57:285–288

    PubMed  CAS  Google Scholar 

  103. Langley SEM, Fry CH (1997) The influence of pH on urinary ionized [Ca2+]: differences between urinary tract stone formers and normal subjects. Br J Urol 79:8–14

    PubMed  CAS  Google Scholar 

  104. Pierratos AE, Khalaff H, Cheng PT, Psihramis K, Jewett MAS (1994) Clinical and biochemical differences in patients with pure calcium oxalate monohydrate and calcium oxalate dihydrate kidney stones. J Urol 151:571–574

    PubMed  CAS  Google Scholar 

  105. Elliot JS, Sharp R, Lewis L (1959) Urinary pH. J Urol 81:339–343

    Google Scholar 

  106. Hallson PC, Rose GA (1977) Seasonal variations in urinary crystals. Br J Urol 49:277–284

    PubMed  CAS  Article  Google Scholar 

  107. Wu W, Gerard D, Nancollas G (1999) Nucleation at surfaces: the importance of interfacial energy. J Am Soc Nephro 10(suppl 14):S355–S358

    Google Scholar 

  108. Ahlstrand C, Tiselius HG (1987) Urine composition and stone formation during treatment with acetazolamide. Scand J Urol Nephrol 21:225–228

    PubMed  CAS  Article  Google Scholar 

  109. Höjgaard I, Fornander AM, Nilsson MA, Tiselius HG (1999) Crystallization during volume reduction of solutions with a composition corresponding to that in the collecting duct: influence of hydroxyapatite seed crystals an urinary macromolecules. Urol Res 27:417–425

    PubMed  Article  Google Scholar 

  110. Landis W, Silver F (2009) Mineral deposition in the extracellular matrices of vertebrate tissues: identification of possible apatite nucleation sites on type I collagen. Cells Tissues Organs 189:20–24

    PubMed  CAS  Article  Google Scholar 

  111. Atmani F, Opalko FJ, Khan SR (1996) Association of urinary macromolecules with calcium oxalate crystals induced in vitro in normal human and rat urine. Urol Res 24:45–50

    PubMed  CAS  Article  Google Scholar 

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

    PubMed  CAS  Article  Google Scholar 

  113. Tiselius HG (1999) Factors influencing the course of calcium oxalate stone disease. Eur Urol 36:363–370

    PubMed  CAS  Article  Google Scholar 

  114. Tiselius HG, Bek-Jensen H, Fornander AM, Nilsson MA (1995) Crystallisation properties in urine from calcium oxalate stone formers. J Urol 154:940–946

    PubMed  CAS  Article  Google Scholar 

  115. Tiselius HG (1991) Aspects on the risk of calcium oxalate crystallisation in urine. Urol Int 47:255–259

    PubMed  CAS  Article  Google Scholar 

  116. Nancollas GH (1983) Crystallization theory relating to urinary stone formation. World J Urol 1:131–137

    Article  Google Scholar 

  117. Berg C, Tiselius HG (1989) The effects of citrate on hydroxyapatite induced calcium oxalate crystallization and on the formation of calcium phosphate crystals. Urol Res 17:167–172

    PubMed  CAS  Article  Google Scholar 

  118. Tiselius HG (2004) Recurrence prevention in patients with urinary tract stone disease. Scientific World Journal 31:417–425

    Google Scholar 

  119. Caudarella R, Vescini F (2009) Urinary citrate and renal stone disease: the preventive role of alkali treatment. Arch Ital Urol Androl 81:182–187

    PubMed  Google Scholar 

  120. Cannon AB, Westropp JL, Ruby AL, Kass PH (2007) Evaluation of trends in urolith composition in cats: 5, 230 cases (1985–2004). J Am Vet Med Assoc 15:570–576

    Article  Google Scholar 

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  1. Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden

    Hans-Göran Tiselius

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Tiselius, HG. A hypothesis of calcium stone formation: an interpretation of stone research during the past decades. Urol Res 39, 231–243 (2011). https://doi.org/10.1007/s00240-010-0349-3

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Keywords

  • Calcium oxalate
  • Calcium phosphate
  • Promoters
  • Inhibitors
  • Nephron
  • Loop of Henle
  • Collecting duct
  • Calices
  • Randall’s plaque
  • Nucleation
  • Growth
  • Aggregation
  • Urinary macromolecules
  • Osteopontin
  • Tamm–Horsfall protein
  • Papilla
  • pH
  • Citrate
  • Ion-strength