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Renal struvite stones—pathogenesis, microbiology, and management strategies

Nature Reviews Urology volume 11, pages 333–341 (2014)Cite this article

Subjects

This article has been updated

Key Points

  • Struvite stones form a subset of kidney stones that are exclusively associated with urease-producing bacteria

  • Stone culture at the time of treatment or urine culture from the renal pelvis provides useful clinical information for directing antibiotic therapy

  • Percutaneous nephrolithotomy (PCNL) is the gold-standard approach for treatment of staghorn infection calculi but other interventions might have an adjunctive role in therapy

  • Residual stone fragments can be removed using urease inhibitors, acidification therapy, dissolution therapy, extracorporeal shockwave lithotripsy, ureteroscopy, PCNL, or anatrophic nephrolithotomy

  • Repeat imaging and urine cultures should be performed within 3 months of the procedure to confirm a stone-free status or identify recurrence

Abstract

Infection stones—which account for 10–15% of all urinary calculi—are thought to form in the presence of urease-producing bacteria. These calculi can cause significant morbidity and mortality if left untreated or treated inadequately; optimal treatment involves complete stone eradication in conjunction with antibiotic therapy. The three key principles of treating struvite stones are: removal of all stone fragments, the use of antibiotics to treat the infection, and prevention of recurrence. Several methods to remove stone fragments have been described in the literature, including the use of urease inhibitors, acidification therapy, dissolution therapy, extracorporeal shockwave lithotripsy, ureteroscopy, percutaneous nephrolithotomy (PCNL), and anatrophic nephrolithotomy. PCNL is considered to be the gold-standard approach to treating struvite calculi, but adjuncts might be used when deemed necessary. When selecting antibiotics to treat infection, it is necessary to acquire a stone culture or, at the very least, urine culture from the renal pelvis at time of surgery, as midstream urine cultures do not always reflect the causative organism.

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Figure 1: The process of biofilm formation.
Figure 2: A proposed algorithm for the management of struvite stones.

Change history

  • 27 May 2014

    In the version of this article initially published online Wai Ho Choy's name was spelled incorrectly. The error has been corrected for the print, HTML and PDF versions of the article.

References

  1. Hesse, A. & Bach, D. Harnsteine, Pathobiochemie and Klinisch-chemische Diagnostik (eds Breuer, H., Buttner, H. & Stamm, D.) (Thieme Verlag, 1982).

    Google Scholar 

  2. Resnick, M. I. Evaluation and management of infection stones. Urol. Clin. North Am. 8, 265–276 (1981).

    CAS  PubMed  Google Scholar 

  3. Lee, M. C. & Bariol, S. V. Changes in upper urinary tract stone composition in Australia over the past 30 years. BJU Int. 112 (Suppl. 2), 65–68 (2013).

    Article  PubMed  Google Scholar 

  4. Shafi, H. et al. Bacteriological study and structural composition of staghorn stones removed by the anatrophic nephrolithotomic procedure. Saudi J. Kidney Dis. Transpl. 24, 418–423 (2013).

    Article  PubMed  Google Scholar 

  5. Koga, S., Arakaki, Y., Matsuoka, M. & Ohyama, C. Staghorn calculi–long-term results of management. Br. J. Urol. 68, 122–124 (1991).

    Article  CAS  PubMed  Google Scholar 

  6. Schwartz, B. F. & Stoller, M. L. Nonsurgical management of infection-related renal calculi. Urol. Clin. North Am. 26, 765–778 (1999).

    Article  CAS  PubMed  Google Scholar 

  7. Evans, K. & Costabile, R. A. Time to development of symptomatic urinary calculi in a high risk environment. J. Urol. 173, 858–861 (2005).

    Article  PubMed  Google Scholar 

  8. Bichler, K. H. et al. Urinary infection stones. Int. J. Antimicrob. Agents 19, 488–498 (2002).

    Article  CAS  PubMed  Google Scholar 

  9. Bhadra, B., Roy, P. & Chakraborty, R. Serratia ureilytica sp. nov., a novel urea-utilizing species. Int. J. Syst. Evol. Microbiol. 55, 2155–2158 (2005).

    Article  CAS  PubMed  Google Scholar 

  10. Mariappan, P., Smith, G., Moussa, S. A. & Tolley, D. A. One week of ciprofloxacin before percutaneous nephrolithotomy significantly reduces upper tract infection and urosepsis: a prospective controlled study. BJU Int. 98, 1075–1079 (2006).

    Article  PubMed  Google Scholar 

  11. Gault, M. H. et al. Bacteriology of urinary tract stones. J. Urol. 153, 1164–1170 (1995).

    Article  CAS  PubMed  Google Scholar 

  12. Akagashi, K. et al. Characteristics of patients with staghorn calculi in our experience. Int. J. Urol. 11, 276–281 (2004).

    Article  PubMed  Google Scholar 

  13. Tavichakorntrakool, R. et al. Extensive characterizations of bacteria isolated from catheterized urine and stone matrices in patients with nephrolithiasis. Nephrol. Dial. Transplant. 27, 4125–4130 (2012).

    Article  PubMed  Google Scholar 

  14. Englert, K. M., McAteer, J. A., Lingeman, J. E. & Williams, J. C. Jr. High carbonate level of apatite in kidney stones implies infection, but is it predictive? Urolithiasis 41, 389–394 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Bazin, D., Daudon, M., Combes, C. & Rey, C. Characterization and some physicochemical aspects of pathological microcalcifications. Chem. Rev. 112, 5092–5120 (2012).

    Article  CAS  PubMed  Google Scholar 

  16. Bazin, D. et al. Absence of bacterial imprints on struvite-containing kidney stones: a structural investigation at the mesoscopic and atomic scale. Urology 79, 786–790 (2012).

    Article  PubMed  Google Scholar 

  17. Margel, D. et al. Clinical implication of routine stone culture in percutaneous nephrolithotomy—a prospective study. Urology 67, 26–29 (2006).

    Article  CAS  PubMed  Google Scholar 

  18. Balk, N., Strohmaier, W., Schmid, M. & Bichler, K. in 2nd European Symposium on Stone Disease (Urological Research, 1990).

    Google Scholar 

  19. Rahman, N. U., Meng, M. V. & Stoller, M. L. Infections and urinary stone disease. Curr. Pharm. Des. 9, 975–981 (2003).

    Article  CAS  PubMed  Google Scholar 

  20. Griffith, D. & Klein, A. in Stones: Clinical management of urolithiasis (eds Roth, R. & Finlayson, B.) 210–227 (Williams & Wilkins, 1983).

    Google Scholar 

  21. Rose, G. in Urinary Stones: Clinical and Laboratory Aspects 257–266 (University Park Press, 1982).

    Google Scholar 

  22. Nickel, J. C., Emtage, J. & Costerton, J. W. Ultrastructural microbial ecology of infection-induced urinary stones. J. Urol. 133, 622–627 (1985).

    Article  CAS  PubMed  Google Scholar 

  23. Nickel, J. C., Olson, M., McLean, R. J., Grant, S. K. & Costerton, J. W. An ecological study of infected urinary stone genesis in an animal model. Br. J. Urol. 59, 21–30 (1987).

    Article  CAS  PubMed  Google Scholar 

  24. Nickel, J. C., Costerton, J. W., McLean, R. J. & Olson, M. Bacterial biofilms: influence on the pathogenesis, diagnosis and treatment of urinary tract infections. J. Antimicrob. Chemother. 33 (Suppl. A), 31–41 (1994).

    Article  PubMed  Google Scholar 

  25. Kajander, E. O. & Ciftcioglu, N. Nanobacteria: an alternative mechanism for pathogenic intra- and extracellular calcification and stone formation. Proc. Natl Acad. Sci. USA 95, 8274–8279 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Raoult, D. et al. Nanobacteria are mineralo fetuin complexes. PLoS Pathog. 4, e41 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Blandy, J. P. & Singh, M. The case for a more aggressive approach to staghorn stones. J. Urol. 115, 505–506 (1976).

    Article  CAS  PubMed  Google Scholar 

  28. Teichman, J. M., Long, R. D. & Hulbert, J. C. Long-term renal fate and prognosis after staghorn calculus management. J. Urol. 153, 1403–1407 (1995).

    Article  CAS  PubMed  Google Scholar 

  29. Wong, H., Riedl, C. & Griffith, D. in Kidney Stones: Medical and Surgical Management (eds Co, F., Favus, M., Pak, C., Parks, J. & Preminger, G.) 941–950 (Raven Press, 1996).

    Google Scholar 

  30. Iqbal, M. W. et al. Contemporary management of struvite stones using combined endourologic and medical treatment: predictors of unfavorable clinical outcome. J. Endourol. http://dx.doi.org/10.1089/end.2013-0257.ECC13.

  31. Marchini, G. S. et al. Absolute Hounsfield unit measurement on noncontrast computed tomography cannot accurately predict struvite stone composition. J. Endourol. 27, 162–167 (2013).

    Article  PubMed  Google Scholar 

  32. Mostafavi, M. R., Ernst, R. D. & Saltzman, B. Accurate determination of chemical composition of urinary calculi by spiral computerized tomography. J. Urol. 159, 673–675 (1998).

    Article  CAS  PubMed  Google Scholar 

  33. Wisenbaugh, E. S., Paden, R. G., Silva, A. C. & Humphreys, M. R. Dual-energy vs conventional computed tomography in determining stone composition. Urology http://dx.doi.org/10.1016/j.urology.2013.12.023.

  34. Streem, S. B., Yost, A. & Dolmatch, B. Combination “sandwich” therapy for extensive renal calculi in 100 consecutive patients: immediate, long-term and stratified results from a 10-year experience. J. Urol. 158, 342–345 (1997).

    Article  CAS  PubMed  Google Scholar 

  35. Tiselius, H. et al. Guidelines on urolithiasis. EUA Guidelines [online], (2013).

    Google Scholar 

  36. Zanetti, G. et al. Infections and urolithiasis: current clinical evidence in prophylaxis and antibiotic therapy. Arch. Ital. Urol. Androl. 80, 5–12 (2008).

    PubMed  Google Scholar 

  37. Charton, M., Vallancien, G., Veillon, B. & Brisset, J. M. Urinary tract infection in percutaneous surgery for renal calculi. J. Urol. 135, 15–17 (1986).

    Article  CAS  PubMed  Google Scholar 

  38. Cadeddu, J. A. et al. Clinical significance of fever after percutaneous nephrolithotomy. Urology 52, 48–50 (1998).

    Article  CAS  PubMed  Google Scholar 

  39. Dogan, H. S. et al. Antibiotic prophylaxis in percutaneous nephrolithotomy: prospective study in 81 patients. J. Endourol. 16, 649–653 (2002).

    Article  PubMed  Google Scholar 

  40. Gonen, M., Turan, H., Ozturk, B. & Ozkardes, H. Factors affecting fever following percutaneous nephrolithotomy: a prospective clinical study. J. Endourol. 22, 2135–2138 (2008).

    Article  PubMed  Google Scholar 

  41. Chen, L. et al. Systemic inflammatory response syndrome after percutaneous nephrolithotomy: an assessment of risk factors. Int. J. Urol. 15, 1025–1028 (2008).

    Article  PubMed  Google Scholar 

  42. Cheung, M. C., Lee, F., Yip, S. K. & Tam, P. C. Outpatient holmium laser lithotripsy using semirigid ureteroscope. Is the treatment outcome affected by stone load? Eur. Urol. 39, 702–708 (2001).

    Article  CAS  PubMed  Google Scholar 

  43. Fernandez, A., Foell, K., Nott, L., Denstedt, J. D. & Razvi, H. Percutaneous nephrolithotripsy in patients with urinary diversions: a case-control comparison of perioperative outcomes. J. Endourol. 25, 1615–1618 (2011).

    Article  PubMed  Google Scholar 

  44. Gutierrez, J. et al. Urinary tract infections and post-operative fever in percutaneous nephrolithotomy. World J. Urol. 31, 1135–1140 (2013).

    Article  PubMed  Google Scholar 

  45. Sharifi Aghdas, F., Akhavizadegan, H., Aryanpoor, A., Inanloo, H. & Karbakhsh, M. Fever after percutaneous nephrolithotomy: contributing factors. Surg. Infect. (Larchmt) 7, 367–371 (2006).

    Article  Google Scholar 

  46. Draga, R. O., Kok, E. T., Sorel, M. R., Bosch, R. J. & Lock, T. M. Percutaneous nephrolithotomy: factors associated with fever after the first postoperative day and systemic inflammatory response syndrome. J. Endourol. 23, 921–927 (2009).

    Article  PubMed  Google Scholar 

  47. Knopf, H. J., Graff, H. J. & Schulze, H. Perioperative antibiotic prophylaxis in ureteroscopic stone removal. Eur. Urol. 44, 115–118 (2003).

    Article  PubMed  Google Scholar 

  48. Tenke, P., Kovacs, B., Benko, R., Ashaber, D. & Nagy, E. Continuous versus intermittent levofloxacin treatment in complicated urinary tract infections caused by urinary obstruction temporarily relieved by foreign body insertion. Int. J. Antimicrob. Agents 28 (Suppl. 1), 82–85 (2006).

    Article  CAS  Google Scholar 

  49. Costantino, G. et al. The antibacterial chemoprophylaxis in ureteroscopy: the employment of the levofloxacin used as switch-therapy versus oral treatment with a single 500 mg once a day. Gazz. Med. Ital. Arch. Sci. Med. 164, 43–46 (2005).

    Google Scholar 

  50. Dincel, C., Ozdiler, E., Ozenci, H., Tazici, N. & Kosar, A. Incidence of urinary tract infections in patients without bacteriuria undergoing SWL: comparison of stone types. J. Endourol. 12, 1–3 (1998).

    Article  CAS  PubMed  Google Scholar 

  51. Pettersson, B. & Tiselius, H. G. Are prophylactic antibiotics necessary during extracorporeal shockwave lithotripsy?. Br. J. Urol. 63, 449–452 (1989).

    Article  CAS  PubMed  Google Scholar 

  52. Bierkens, A. et al. The value of antibiotic prophylaxis during extracorporeal shockwave lithotripsy in the prevention of urinary tract infections in patients with urine proven sterile prior to treatment. Eur. Urol. 31, 30–35 (1997).

    Article  CAS  PubMed  Google Scholar 

  53. Turk, C. et al. Guidelines on urolithiasis. EUA Guidelines [online], (2013).

    Google Scholar 

  54. Preminger, G. M. et al. Chapter 1: AUA guideline on management of staghorn calculi: diagnosis and treatment recommendations. J. Urol. 173, 1991–2000 (2005).

    Article  PubMed  Google Scholar 

  55. Paterson, R., Fernandez, A., Razvi, H. & Sutton, R. Evaluation and medical management of the kidney stone patient. CUA Guidelines. http://www.cua.org/userfiles/files/guidelines/ksm_2011_en.pdf (2013).

  56. Healy, K. A. & Ogan, K. Pathophysiology and management of infectious staghorn calculi. Urol. Clin. North Am. 34, 363–374 (2007).

    Article  PubMed  Google Scholar 

  57. Orsola, A. et al. Staghorn calculi in children: treatment with monotherapy extracorporeal shock wave lithotripsy. J. Urol. 162, 1229–1233 (1999).

    Article  CAS  PubMed  Google Scholar 

  58. Meretyk, S. et al. Complete staghorn calculi: random prospective comparison between extracorporeal shock wave lithotripsy monotherapy and combined with percutaneous nephrostolithotomy. J. Urol. 157, 780–786 (1997).

    Article  CAS  PubMed  Google Scholar 

  59. Delaney, C. P., Creagh, T. A., Smith, J. M. & Fitzpatrick, J. M. Do not treat staghorn calculi by extracorporeal shockwave lithotripsy alone! Eur. Urol. 24, 355–357 (1993).

    Article  CAS  PubMed  Google Scholar 

  60. Gleeson, M. J. & Griffith, D. P. Extracorporeal shockwave lithotripsy monotherapy for large renal calculi. Br. J. Urol. 64, 329–332 (1989).

    Article  CAS  PubMed  Google Scholar 

  61. Lam, H. S. et al. Staghorn calculi: analysis of treatment results between initial percutaneous nephrostolithotomy and extracorporeal shock wave lithotripsy monotherapy with reference to surface area. J. Urol. 147, 1219–1225 (1992).

    Article  CAS  PubMed  Google Scholar 

  62. Esen, A. A., Kirkali, Z. & Guler, C. Open stone surgery: is it still a preferable procedure in the management of staghorn calculi? Int. Urol. Nephrol. 26, 247–253 (1994).

    Article  CAS  PubMed  Google Scholar 

  63. Koko, A. K., Onuora, V. C., Al Turki, M. A., Mesbed, A. H. & Al Jawini, N. A. Extracorporeal shockwave lithotripsy monotherapy is not adequate for management of staghorn renal calculi. Saudi J. Kidney Dis. Transpl. 14, 487–491 (2003).

    PubMed  Google Scholar 

  64. El-Assmy, A. et al. Extracorporeal shock-wave lithotripsy monotherapy of partial staghorn calculi. Prognostic factors and long-term results. Scand. J. Urol. Nephrol. 40, 320–325 (2006).

    Article  PubMed  Google Scholar 

  65. Marguet, C. G. et al. Simultaneous combined use of flexible ureteroscopy and percutaneous nephrolithotomy to reduce the number of access tracts in the management of complex renal calculi. BJU Int. 96, 1097–1100 (2005).

    Article  PubMed  Google Scholar 

  66. Landman, J. et al. Combined percutaneous and retrograde approach to staghorn calculi with application of the ureteral access sheath to facilitate percutaneous nephrolithotomy. J. Urol. 169, 64–67 (2003).

    Article  PubMed  Google Scholar 

  67. Hamamoto, S. et al. Endoscopic combined intrarenal surgery for large calculi: simultaneous use of flexible ureteroscopy and mini-percutaneous nephrolithotomy overcomes the disadvantageous of percutaneous nephrolithotomy monotherapy. J. Endourol. 28, 28–33 (2014).

    Article  PubMed  Google Scholar 

  68. Assimos, D. G. Anatrophic nephrolithotomy. Urology 57, 161–165 (2001).

    Article  CAS  PubMed  Google Scholar 

  69. Assimos, D. G. et al. A comparison of anatrophic nephrolithotomy and percutaneous nephrolithotomy with and without extracorporeal shock wave lithotripsy for management of patients with staghorn calculi. J. Urol. 145, 710–714 (1991).

    Article  CAS  PubMed  Google Scholar 

  70. Paik, M. L., Wainstein, M. A., Spirnak, J. P., Hampel, N. & Resnick, M. I. Current indications for open stone surgery in the treatment of renal and ureteral calculi. J. Urol. 159, 374–378 (1998).

    Article  CAS  PubMed  Google Scholar 

  71. Al-Kohlany, K. M. et al. Treatment of complete staghorn stones: a prospective randomized comparison of open surgery versus percutaneous nephrolithotomy. J. Urol. 173, 469–473 (2005).

    Article  PubMed  Google Scholar 

  72. Wong, C. & Leveillee, R. J. Single upper-pole percutaneous access for treatment of > or = 5-cm complex branched staghorn calculi: is shockwave lithotripsy necessary? J. Endourol. 16, 477–481 (2002).

    Article  PubMed  Google Scholar 

  73. Aron, M. et al. Multi-tract percutaneous nephrolithotomy for large complete staghorn calculi. Urol. Int. 75, 327–332 (2005).

    Article  PubMed  Google Scholar 

  74. Wang, Y. et al. Standard-tract combined with mini-tract in percutaneous nephrolithotomy for renal staghorn calculi. Urol. Int. http://dx.doi.org/10.1159/000354427 (2014).

  75. Griffith, D. P. et al. Randomized, double-blind trial of Lithostat (acetohydroxamic acid) in the palliative treatment of infection-induced urinary calculi. Eur. Urol. 20, 243–247 (1991).

    Article  CAS  PubMed  Google Scholar 

  76. Griffith, D. P., Khonsari, F., Skurnick, J. H. & James, K. E. A randomized trial of acetohydroxamic acid for the treatment and prevention of infection-induced urinary stones in spinal cord injury patients. J. Urol. 140, 318–324 (1988).

    Article  CAS  PubMed  Google Scholar 

  77. Williams, J. J., Rodman, J. S. & Peterson, C. M. A randomized double-blind study of acetohydroxamic acid in struvite nephrolithiasis. N. Engl. J. Med. 311, 760–764 (1984).

    Article  CAS  PubMed  Google Scholar 

  78. Chauhan, C. K. & Mihir, J. J. In vitro crystallization, characterization and growth-inhibition study of urinary type struvite crystals. J. Cryst. Growth 362, 330–337 (2013).

    Article  CAS  Google Scholar 

  79. Prywer, J. & Torzewska, A. Effect of curcumin against proteus mirabilis during crystallization of struvite from artificial urine. Evid. Based Complement. Alternat. Med. 2012, 862794 (2012).

    Article  PubMed  Google Scholar 

  80. Daglia, M. Polyphenols as antimicrobial agents. Curr. Opin. Biotechnol. 23, 174–181 (2012).

    Article  CAS  PubMed  Google Scholar 

  81. Torzewska, A. & Rozalski, A. Inhibition of crystallization caused by Proteus mirabilis during the development of infectious urolithiasis by various phenolic substances. Microbiol. Res. http://dx.doi.org/10.1016/j.micres.2013.09.020.

  82. Hellstrom, J. The significance of staphylococci in the development and treatment of renal and ureteral stones. Br. J. Urol. 10, 348–372 (1938).

    Article  Google Scholar 

  83. Shortliffe, L. M. & Spigelman, S. S. Infection stones. Evaluation and management. Urol. Clin. North Am. 13, 717–726 (1986).

    CAS  PubMed  Google Scholar 

  84. Dretler, S. P. & Pfister, R. C. Primary dissolution therapy of struvite calculi. J. Urol. 131, 861–863 (1984).

    Article  CAS  PubMed  Google Scholar 

  85. Fam, B., Rossier, A. B., Yalla, S. & Berg, S. The role of hemiacidrin in the management of renal stones in spinal cord injury patients. J. Urol. 116, 696–698 (1976).

    Article  CAS  PubMed  Google Scholar 

  86. Tiselius, H. G., Hellgren, E., Andersson, A., Borrud-Ohlsson, A. & Eriksson, I. Minimally invasive treatment of infection staghorn stones with shock wave lithotripsy and chemolysis. Scand. J. Urol. Nephrol. 33, 286–290 (1999).

    Article  CAS  PubMed  Google Scholar 

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  1. The Stone Centre at Vancouver General Hospital, Jack Bell Research Centre, 2660 Oak Street, Vancouver, V6H 3Z6, BC, Canada

    Ryan Flannigan, Wai Ho Choy, Ben Chew & Dirk Lange

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R.F. and D.L. researched, wrote, edited, reviewed, and discussed the Review with colleagues. W.H.C. helped to research and edit the article. B.C. contributed towards writing and editing.

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Correspondence to Dirk Lange.

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B.C. declares consulting associations with Boston Scientific, Cook Medical, Olympus ACMI, PercSys and Bard Medical. D.L. declares consulting associations with Boston Scientific, Olympus, Cook Medical, PercSys, and Bard Medical. R.F. and W.H.C. declare no competing interests.

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Flannigan, R., Choy, W., Chew, B. et al. Renal struvite stones—pathogenesis, microbiology, and management strategies. Nat Rev Urol 11, 333–341 (2014). https://doi.org/10.1038/nrurol.2014.99

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