Skip to main content
SpringerLink
Log in

Glycosaminoglycans and other sulphated polysaccharides in calculogenesis of urinary stones

  • Published:
World Journal of Urology Aims and scope Submit manuscript

Summary

Naturally occurring glycosaminoglycans (GAGs) and other, semisynthetic, sulphated polysaccharides are thought to play an important role in urolithiasis. Processes involved in urinary stone formation are crystallization and crystal retention. Oxalate transport and renal tubular cell injury are determining factors in these processes. In this article experimental results concerning the possible mechanisms of action of GAGs and other sulphated polysaccharides are reviewed. GAGs are inhibitors of crystal growth and agglomeration and possibly also of nucleation. They can prevent crystal adherence, correct an abnormal oxalate flux and prevent renal tubular cell damage.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Angell AH, Resnick MI (1989) Surface interaction between glycosaminoglycans and calcium oxalate. J Urol 141:1255–1258

    Google Scholar 

  2. Baggio B, Gambaro G, Ossi E, Favaro S, Borsati A (1983) Increased urinary excretion of renal enzymes in idiopathic calcium oxalate nephrolithiasis. J Urol 129:1161–1162

    CAS  PubMed  Google Scholar 

  3. Baggio B, Gambaro G, Marchini F, Cicerello E, Tenconi R, Clementi M, Borsati A (1986) An inheritable anomaly of red-cell oxalate transport in “primary” calcium nephrolithiasis correctable with diuretics. N Engl J Med 314:599–604

    Google Scholar 

  4. Baggio B, Gambaro G, Marchini F, Marzaro G, Williams HE, Borsati A (1991) Correction of erythrocyte abnormalities in idiopathic calcium-oxalate nephrolithiasis and reduction of urinary oxalate by oral glycosaminoglycans. Lancet 338:403–405

    Google Scholar 

  5. Bek-Jensen H, Tiselius HG (1991) Inhibition of calcium oxalate crystallization by urinary macromolecules. Urol Res 19:165–169

    Google Scholar 

  6. Boevé ER, Cao LC, Schröder FH, Ketelaars GAM, Vermey M, Bruijn WC de (1990) The influence of 3 exogenous glycosaminoglycans on the experimental induction of microliths in rats. Urol Res 18:62

    Google Scholar 

  7. Boevé ER, Cao LC, Bruijn WC de, Robertson WG, Schröder FH (1993) The effect of two semi-synthetic glycosaminoglycans (G871, G872) on the zeta potential of calcium phosphate crystals and on growth and agglomeration. J Urol 149:441A

    Google Scholar 

  8. Boevé ER, Ketelaars GAM, Vermeij M, Cao LC, Schröder FH, Bruijn WC de (1993) An ultrastructural study of experimentally induced microliths in rat proximal and distal tubules. J Urol 149:893–899

    CAS  PubMed  Google Scholar 

  9. Bowyer RC, Brockis JG, McCulloch RK (1979) Glycosaminoglycans as inhibitors of calcium oxalate crystal growth and aggregation. Clin Chim Acta 95:23–28

    Google Scholar 

  10. Bruijn WC de, Ketelaars GAM, Boevé ER, Sorber CWJ, Cao LC, Schröder FH (1993) Electron energy-loss spectroscopical and image analysis of experimentally induced rat mocroliths. J Urol 149:900–905

    Google Scholar 

  11. Butt AJ (1952) Role of protective urinary colloids in prevention of lithiasis. J Urol 67:450–459

    Google Scholar 

  12. Cao LC, Boevé ER, Schröder FH (1991) The mechanisms of action of glycosaminoglycans (GAGs) in calcium oxalate stone prevention: a review. J Lithotripsy Stone Dis 3:324–333

    Google Scholar 

  13. Cao LC, Boevé ER, Schröder FH, Robertson WG, Ketelaars GAM, Bruijn WC de (1992) The effect of two new semi-synthetic glycosaminoglycans (G871, G872) on the zeta potential of calcium oxalate crystals and on growth and agglomeration. J Urol 147:1643–1646

    Google Scholar 

  14. Caudarella R, Stefani F, Rizzoli E, Malavolta N, D'Antuono G (1983) Preliminary results of glycosaminoglycan excretion in normal and stone forming subjects: relationship with uric acid excretion. J Urol 129:665–667

    Google Scholar 

  15. Danielson BG, Fellström B, Wikström B (1989) Glycosaminoglycans as inhibitors of renal stone formation. In: Walker VR, Sutton RAL, Cameron ECB, Pak CYC, Robertson WG (eds). Urolithiasis. Plenum, New York, pp 101–104

    Google Scholar 

  16. Dawes J, Hodson BA, Pepper DS (1989) The absorption, clearance and metabolic fate of dermatan sulphate administerd to man — studies using a radioiodinated derivative. Thromb Haemos 62:945–949

    Google Scholar 

  17. DiFerrante N, Rich C (1956) The determination of acid aminopolysaccharide in urine. J Lab Clin Med 48:491–494

    Google Scholar 

  18. Drach GW, Sarig S, Randolph AD, Thorson S (1982) The paradox of inhibition and enhancement of the formation of urinary stones. Urol Res 10:165–168

    Google Scholar 

  19. Fellström B, Danielson BG, Ljunghall S, Wikström B (1985) The inhibition of calcium oxalate crystal growth by chondroitin sulphates, heparin, pentosan polysulphate and Tamm-Horsfall glycoprotein. In: Schwille PO, Smith LH, Robertson WG, Vahlensieck W (eds) Urolithiasis and related clinical research. Plenum, New York, pp 887–890

    Google Scholar 

  20. Fellström B, Lindsjö M, Danielson BG, Ljunghall S, Wikström B (1986) Binding of glycosaminoglycans to sodium urate and uric acid crystals. Clin Sci 71:61–64

    Google Scholar 

  21. Fellström B, Lindsjö M, Danielson BG, Karlsson FA, Ljunghall S (1989) Binding of glycosaminoglycan inhibitors to calcium oxalate crystals in relation to ionic strength. Clin Chim Acta 180:213–220

    Google Scholar 

  22. Finlayson B, Du Bois L (1978) Adsorption of heparin on sodium acid urate. Clin Chim Acta 84:203–206

    Google Scholar 

  23. Finlayson B, Khan SR, Hackett RL (1984) Mechanisms of stone formation — an overview. Scan Microsc Int 3:1419–1425

    Google Scholar 

  24. Gambaro G, Cavazzana AO, Luzi P, Piccoli A, Borsati A, Crepaldi G, Marchi E, Venturini AP, Baggio B (1992) Glycosaminoglycans prevent morphological renal alterations and albuminuria in diabetic rats. Kidney Int 42:285–291

    Google Scholar 

  25. Gianotti M, Genestar C, Palou A, Pons A, Conte A, Grases F (1989) Investigation of GAGs on 24-hour and 2-hour urines from calcium oxalate stone formers and healthy subjects. Int Urol Nephrol 21:281–288

    Google Scholar 

  26. Gill WB, Ruggiero KJ, Straus FH (1980) Crystallization studies in an urothelial-lined living test tube (the catheterized female rat bladder). I. Calcium oxalate crystal adhesion to the chemically injured rat bladder. Invest Urol 17:259–261

    Google Scholar 

  27. Gill WB, Ruggiero KJ, Fromez MC (1980) Elevation of the metastable limits and absence of container surface nucleation for calcium oxalate crystallization in a urothelial-lined system as compared to glass containers. Invest Urol 18:158–160

    Google Scholar 

  28. Gill WB, Jones KW, Ruggiero KJ (1982) Protective effects of heparin and other sulfated glycosaminoglycans on crystal adhesion to injured urothelium. J Urol 127:152–154

    Google Scholar 

  29. Goldberg JM, Cotlier E (1972) Specific isolation and analysis of mucopolysaccharides (glycosaminoglycans) from human urine. Clin Chim Acta 41:19–27

    Google Scholar 

  30. Grases F, Costa-Bauzá A, March JG (1991) Glycosaminoglycans, uric acid and calcium oxalate urolithiasis. Urol Res 19:375–380

    Google Scholar 

  31. Grover PK, Ryall RL, Marshall VR (1992) Calcium oxalate crystallization in urine: role of urate and glycosaminoglycans. Kidney Int 41:149–154

    Google Scholar 

  32. Hansen NM, Felix R, Bisaz S, Fleisch H (1976) Aggregation of hydroxyapatite crystals. Biochim Biophys Acta 451:549–559

    Google Scholar 

  33. Hesse A, Wuzel H, Vahlensieck W (1986) The excretion of glycosaminoglycans in the urine of calcium-oxalate-stone patients and healthy persons. Urol Int 41:81–87

    Google Scholar 

  34. Hesse A, Wuzel H, Krampitz G, Vahlensieck W (1987) Experimental determination of the kinetics of calcium-binding with chondroitin sulphate and the effects of uric acid on this process. Urol Res 15:93–97

    Google Scholar 

  35. Hesse A, Wuzel H, Vahlensieck W (1991) Significance of glycosaminoglycans for the formation of calcium oxalate stones. Am J Kidney Dis 17:414–419

    Google Scholar 

  36. Khan SR, Shevock PN, Hackett RL (1992) Acute hyperoxaluria, renal injury and calcium oxalate urolithiasis. J Urol 147:226–230

    CAS  PubMed  Google Scholar 

  37. Kerby GP (1954) The excretion of glucuronic acid and of acid mucopolysaccharides in normal human urine. J Clin Invest 33:1168–1174

    Google Scholar 

  38. Kohri K, Garside J, Blacklock NJ (1989) The effect of glycosaminoglycans on the crystallisation of calcium oxalate. Br J Urol 63:584–590

    Google Scholar 

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

    Google Scholar 

  40. Kumar S, Sigmon D, Miller T, Carpenter B, Khan S, Malhotra R, Scheid C, Menon M (1991) A new model of nephrolithiasis involving tubular dysfunction/injury. J Urol 146:1384–1389

    Google Scholar 

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

    Google Scholar 

  42. Lieske JC, Toback FG (1993) Regulation of renal epithelial cell endocytosis of calcium oxalate monohydrate crystals. Am J Physiol [F] 264:800–807

    Google Scholar 

  43. Mandel NS, Mandel GS, Hasegawa AT (1987) The effect of some urinary stone inhibitors on membrane interaction potentials of stone crystals. J Urol 138:557–562

    Google Scholar 

  44. Martin X, Werness PG, Bergert JH, Smith LH (1984) Pentosan polysulfate as an inhibitor of calcium oxalate crystal growth. J Urol 132:786–788

    Google Scholar 

  45. MacGregor IR, Dawes J, Paton L, Pepper DS, Prowse CV, Smith M (1984) Metabolism of sodium pentosan polysulphate in man — catabolism of iodinated derivatives. Thromb Haemost 51:321–325

    Google Scholar 

  46. McLean RJC, Downey J, Claphan L, Nickel JC (1990) Influence of chondroitin sulphate, heparin sulphate, and citrate on Proteus mirabilis-induced struvite crystallization in vitro. J Urol 144:1267–1271

    Google Scholar 

  47. Michelacci YM, Boim MA, Bergamaschi CT, Rovigatti RM, Schor N (1992) Possible role for chondroitin sulfate in urolithiasis: in vivo studies in an experimental model. Clin Chim Acta 208:1–8

    Google Scholar 

  48. Miyazawa K, Suzuki K, Tsugawa R (1991) A study of crystallization on urolithiasis in vitro (in Japanese). Hinyokika-kiyo 37:1091–1096

    Google Scholar 

  49. Monis B, Dorfman HD (1967) Some histochemical observations on transitional epithelium of man. J Histochem Cytochem 15:475–481

    Google Scholar 

  50. Newton DJ, Scott JE, Ahmad S (1979) Circadian rhythms and the urinary excretion of acid glycosaminoglycans in normal human adults. Connect Tissue Res 7:47–55

    Google Scholar 

  51. Norman RW, Scurr DS, Robertson WG, Peacock M (1984) Inhibition of calcium oxalate crystallization by pentosan polysulphate in control subjects and stone formers. Br J Urol 56:594–598

    Google Scholar 

  52. Norman RW, Scurr DS, Robertson WG, Peacock M (1985) Sodium pentosan polysulphate as a polyanionic inhibitor of calcium oxalate crystallization in vitro and in vivo. Clin Sci 68:369–371

    Google Scholar 

  53. Odlind L, Dencker L, Tengblad A (1987) Preferential localization of 3H-pentosanpolysulphate to the urinary tract in rats. Pharmacol Toxicol 61:162–166

    Google Scholar 

  54. Osswald H, Weinheimer G, Schütt ID, Ernst W (1989) Effective prevention of calcium-oxalate crystal formation in vitro and in vivo by pentosan polysulfate. In: Walker VR, Sutton RAL, Cameron ECB, Pak CYC, Robertson WG (eds) Urolithiasis. Plenum, New York, pp 141–144

    Google Scholar 

  55. Pantazopoulos D, Legakis N, Antonakopoulos G, Sofras F, Dimopoulos C (1987) The effect of pentosanpolysulphate and carbenoxolone on bacterial adherence to the injured urothelium. Br J Urol 59:423–426

    Google Scholar 

  56. Parsons CL (1982) Prevention of urinary tract infection by the exogenous glycosaminoglycan sodium pentosan polysulfate. J Urol 172:167–169

    Google Scholar 

  57. Parsons CL, Greenspan C, Moore SW, Mulholland SG (1977) Role of surface mucin in primary antibacterial defence of bladder. Urology 9:48–52

    Google Scholar 

  58. Parsons CL, Schmidt JD, Pollen JJ (1983) Successful treatment of interstitial cystitis with sodium pentosanpolysulphate. J Urol 130:51–53

    Google Scholar 

  59. Parsons CL, Danielson B, Fellström B (1985) Inhibition of sodium urate crystal adherence to bladder surface by polysaccharide. J Urol 134:614–616

    Google Scholar 

  60. Riese RJ, Mandel NS, Wiessner JH, Mandel GS, Becker CG, Kleinman JG (1992) Cell polarity and calcium oxalate crystal adherence to cultured collecting duct cells. Am J Physiol [F] 262:177–184

    Google Scholar 

  61. Robertson WG, Scurr DS (1986) Modifiers of calcium oxalate crystallization found in urine. I. Studies with a continuous crystallizer using an artificial urine. J Urol 135:1322–1326

    Google Scholar 

  62. Robertson WG, Peacock M, Nordin BEC (1973) Inhibitors of the growth and aggregation of calcium oxalate crystals in vitro. Clin Chim Acta 43:31–37

    Google Scholar 

  63. Robertson WG, Knowles F, Peacock M (1976) Urinary mucopolysaccharide inhibitors of calcium oxalate crystallization. In: Fleisch H, Robertson WG, Smith LH, Vahlensieck W (eds) Urolithiasis research. Plenum, New York London, pp 331–334

    Google Scholar 

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

    Google Scholar 

  65. Ryall RL, Marshall VR (1983) The value of the 24-hour urine analysis in the assessment of stone-formers attending a general hospital outpatient clinic. Br J Urol 55:1–5

    Google Scholar 

  66. Ryall RL, Harnett RM, Marshall VR (1981) The effect of urine, pyrophosphate, citrate, magnesium and glycosaminoglycans on the growth and aggregation of calcium oxalate crystals in vitro. Clin Chim Acta 112:349–356

    Google Scholar 

  67. Ryall RL, Harnett RM, Marshall VR (1986) The effect of monosodium urate on the capacity of urine, chondroitin sulphate and heparin to inhibit calcium oxalate crystal growth and aggregation. J Urol 135:174–177

    Google Scholar 

  68. Sakhaee K, Nicar MJ, Brater DC, Pak CYC (1985) Exaggerated natri-uretic and calciuric responses to hydrochlorothiazide in renal hypercalciuria but not in absorptive hypercalciuria. J Clin Endocrinol Metab 61:825–829

    Google Scholar 

  69. Smith C (1985) 14C-Calcium oxalate (CaOx) adherence in the rat bladder. In: Schwille PO, Smith LH, Robertson WG, Vahlensieck W (eds) Urolithiasis and related clinical research. Plenum, New York, pp 949–952

    Google Scholar 

  70. Subha K, Varalakshmi P (1993) Alteration in some risk ractors and urinary enzymes in urolithiatic rats treated with sodium pentosan polysulphate. Biochem Mol Biol Int 29:271–280

    Google Scholar 

  71. Subha K, Varalakshmi P (1993) Changes in renal tissue glycosaminoglycans in urolithiatic rats treated with sodium pentosan polysulphate. Med Sci Res 21:233–234

    Google Scholar 

  72. Verkoelen CF, Romijn JC, Bruijn WC de, Boevé ER, Cao LC, Schröder FH (1993) Oxalate handling and interaction with calcium oxalate crystals by renal epithelial cells cultured on porous supports. J Urol 149:439A

    Google Scholar 

  73. Yamaguchi S, Yoshioka T, Utsunomiya M, Koide T, Osafune M, Okuyama A, Sonoda T (1993) Heparan sulfate in the stone matrix and its inhibitory effect on calcium oxalate crystallization. Urol Res 21:187–192

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Urology, Academic Hospital Dijkzigt, Erasmus University, Rotterdam, The Netherlands

    E. R. Boevé, L. C. Cao, C. F. Verkoelen, J. C. Romijn, W. C. de Bruijn & F. H. Schröder

  2. the AEM-Unit, Clinical Pathological Institute, Erasmus University, Rotterdam, The Netherlands

    E. R. Boevé, L. C. Cao, C. F. Verkoelen, J. C. Romijn, W. C. de Bruijn & F. H. Schröder

Authors
  1. E. R. Boevé
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. L. C. Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C. F. Verkoelen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J. C. Romijn
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. W. C. de Bruijn
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. F. H. Schröder
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Boevé, E.R., Cao, L.C., Verkoelen, C.F. et al. Glycosaminoglycans and other sulphated polysaccharides in calculogenesis of urinary stones. World J Urol 12, 43–48 (1994). https://doi.org/10.1007/BF00182050

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00182050

Keywords

Search

Navigation